The Potential of Whole Body Vibration Training during 14
Transcrição
The Potential of Whole Body Vibration Training during 14
Aus dem Institut für Trainingswissenschaft und Sportinformatik der Deutschen Sporthochschule Köln Geschäftsführender Leiter: Prof. Dr. Dr. h.c. mult. Joachim Mester The Potential of Whole Body Vibration Training during 14-Days of 6°-Head Down Tilt Bed Rest to Counteract Effects on Muscle Performance, Balance and Articular Cartilage von der Deutschen Sporthochschule Köln zur Erlangung des akademischen Grades Doktorin der Sportwissenschaft genehmigte Dissertation vorgelegt von Dipl. – Sportwiss. Anna-Maria Liphardt aus Eschwege Köln 2008 Erster Gutachter: Univ.-Prof Dr. Dr. h.c. mult. Joachim Mester, Institut für Trainingswissenschaft und Sportinformatik, Deutsche Sporthochschule Köln Zweite Gutachterin: PD Dr. Martina Heer, Institut für Luft- und Raumfahrtmedizin, Deutsches Zentrum für Luft- und Raumfahrt, Köln Vorsitzende des Promotionsausschusses: Univ.-Prof.’in Dr. Ilse Hartmann-Tews Tag der mündlichen Prüfung: 21. Juli 2008 Erklärung gemäß § 5 Abs. 3: Diese Dissertation wurde an noch keiner anderen Stelle zum Zwecke der Promotion vorgelegt Köln, den 30.01.2008 ___________________________________________________________________ Dipl.-Sportwiss. Anna-Maria Liphardt Erklärung gemäß § 5 Abs. 4: Vor diesem angestrebten Promotionsverfahren habe ich keine anderen Promotionsversuche begonnen und keine Promotionsversuche sind fehlgeschlagen. Köln, den 30.01.2008 ___________________________________________________________________ Dipl.-Sportwiss. Anna-Maria Liphardt Eidesstattliche Versicherung: Hierdurch versichere ich an Eides Statt: Ich habe diese Arbeit selbständig und nur unter Benutzung der angegebenen Quellen angefertigt; sie hat noch keiner anderen Stelle zur Prüfung vorgelegen. Wörtlich übernommene Textstellen, auch Einzelsätze oder Teile davon, sind als Zitate kenntlich gemacht worden. Köln, den 30.01.2008 ___________________________________________________________________ Dipl.-Sportwiss. Anna-Maria Liphardt meinem Vater Content 1 Introduction ......................................................................................................... 1 2 Background......................................................................................................... 3 2.1 2.1.1 Microgravity ............................................................................................ 3 2.1.2 Ground Based Models............................................................................ 4 2.2 Humans in Space – Physiological Effects .................................................. 6 2.2.2 Skeletal Muscle Performance................................................................. 7 2.2.3 Balance .................................................................................................. 8 2.2.4 Cartilage ................................................................................................. 8 2.3 3 Microgravity and Ground Based Models .................................................... 3 Vibration Training ..................................................................................... 10 2.3.1 Physics of Vibration .............................................................................. 10 2.3.2 Mechanical Properties of the Human Body .......................................... 12 2.3.3 Classification of Vibration Training ....................................................... 12 2.3.4 Biological Adaptation to Vibration Training........................................... 14 2.4 Health Risks ............................................................................................. 23 2.5 General Hypotheses................................................................................. 26 General Methods .............................................................................................. 29 3.1 Study Design ............................................................................................ 29 3.2 Study Location.......................................................................................... 31 3.3 Population ................................................................................................ 31 3.3.1 Recruitment Process ............................................................................ 31 3.3.2 Subjects................................................................................................ 32 3.4 Vibration Training Intervention ................................................................. 33 3.4.1 Vibration Training Devise ..................................................................... 33 3.4.2 Vibration Training Protocol ................................................................... 34 3.5 Diet ........................................................................................................... 36 4 3.5.1 Meal Schedule...................................................................................... 36 3.6.1 Nutrient Intake ...................................................................................... 36 3.6 Environmental Conditions ........................................................................ 37 3.7 Physiotherapy........................................................................................... 37 3.8 General Statistics ..................................................................................... 37 Muscle Performance ......................................................................................... 40 4.1 4.1.1 Immobilization / Spaceflight.................................................................. 40 4.1.2 Countermeasures ................................................................................. 42 4.1.3 Vibration Training ................................................................................. 42 4.1.4 Purpose of the Study and Hypotheses ................................................. 44 4.2 Specific Methods ...................................................................................... 45 4.2.1 Muscle Performance Testing................................................................ 45 4.2.2 Statistical analyses ............................................................................... 47 4.3 Results ..................................................................................................... 48 4.4 Discussion ................................................................................................ 50 4.4.1 5 Specific Background................................................................................. 40 Limitations of the Design ...................................................................... 53 Balance ............................................................................................................. 55 5.1 Specific Background................................................................................. 55 5.1.1 General Physiology .............................................................................. 55 5.1.2 Adaptation during Spaceflight and Immobilization................................ 57 5.1.3 Vibration Training ................................................................................. 60 5.1.4 Purpose of the Study and Hypotheses ................................................. 61 5.2 Methods.................................................................................................... 63 5.2.1 Posturomed® Device ............................................................................ 63 5.2.2 Test Protocol ........................................................................................ 65 5.2.3 Statistics ............................................................................................... 67 5.2.4 Association with Data Loss................................................................... 68 5.2.5 Malfunction of the Sensors of the ‘Posturomed®’ ................................. 68 5.3 5.3.1 Holding Time ........................................................................................ 69 5.3.2 Displacement of the Platform ............................................................... 70 5.3.3 Correlation of the Parameters Displacement and Holding Time .......... 72 5.4 6 Results ..................................................................................................... 69 Discussion ................................................................................................ 73 5.4.1 Limitations of the Design ...................................................................... 77 5.4.2 Conclusion and Future Work ................................................................ 78 Cartilage Health ................................................................................................ 79 6.1 Specific Background................................................................................. 79 6.1.1 Cartilage Morphology and Loading....................................................... 79 6.1.2 Cartilage Oligometric Matrix Protein..................................................... 80 6.1.3 Vibration Training ................................................................................. 81 6.1.4 Purpose of the Study and Hypotheses ................................................. 81 6.2 Specific Methods ...................................................................................... 83 6.2.1 MR-Imaging .......................................................................................... 83 6.2.2 Three-dimensional (3D) Cartilage Model.............................................. 83 6.2.3 Cartilage Thickness Measurement ....................................................... 84 6.2.4 Blood .................................................................................................... 84 6.2.5 Statistical Analysis................................................................................ 84 6.3 Results ..................................................................................................... 85 6.3.1 Cartilage Thickness .............................................................................. 85 6.3.2 Serum COMP Concentration................................................................ 86 6.4 Discussion ................................................................................................ 88 7 General Discussion........................................................................................... 92 8 Summary........................................................................................................... 95 9 Zusammenfassung ........................................................................................... 98 10 References .................................................................................................... 101 11 APPENDIX – Publications related to the VBR-Study .................................... 112 12 Danksagung .................................................................................................. 114 13 Curriculum Vitae............................................................................................ 116 1 Introduction 1 1 Introduction Planning and executing of manned interplanetary missions are two of the most challenging and important tasks in space life science over the next thirty years. The technical development of space crafts, capable of transporting humans to the Moon or Mars, will be a monumental task. Additionally, strategies must be developed to enable humans to live in space for an extended period of time allowing traveling to another planet and back to Earth. A microgravity environment is generated by a lack of gravitational forces and by inactivity generally of the whole body and specifically the lower extremities. This leads to adaptation processes that are of catabolic nature in the musculoskeletal system. Currently, the duration of a regular shift for a crew member on board the International Space Station is about six months. The longest manned mission to date lasted 437 days which is approximately only one half of the length of a future mission to Mars. Although training regiments during space flight are continually improving, the deconditioning in microgravity cannot yet be avoided. Consequently, the quest for optimized exercise regiments remains a continuous process with the ultimate goal to develop a training protocol that is not only intense but also short in duration while affecting as many structures and tissues as possible, mainly the musculoskeletal system but also the cardio-vascular system. Whole body vibration training has been proposed as an amendment to traditional strength training in the past decade. There is scientific evidence to support the stimulation of the anabolic processes in skeletal muscle and bone. However, many positive effects have been stated so far without scientific approval or evidence. Weight based strength training is not applicable in space, as dumbbells are also weightless in microgravity. In contrast, whole body vibration could technically be applied in space as it functions on the basis of acceleration of mass. Since technical developments for space flight are rather expensive, the effectiveness and feasibility of innovative and improved training methods are usually determined in ground based models prior to technical developments being finalized for implementation in space. The purpose of this doctoral thesis is to test the potential of whole body vibration training to counteract the effects of 14-days of head down tilt bed rest on the human body with a focus on the musculoskeletal system. At the Institute of Aerospace Medicine of the German Aerospace Centre (DLR) in Cologne, Germany, a bed rest 1 Introduction 2 study was performed to test the integrative effect of vibration training during a period of immobilization. Specifically, a series of experiments were performed to investigate the effects of vibration training on the morphology of skeletal muscle, bone and knee cartilage, the performance of balance and the cardio-vascular system. Following the introduction, chapter 2 will give a general background on the effects of microgravity on the human body and describe the current knowledge on vibration training. Chapter 3 describes the overall hypothesis and the methods followed by the specific experiments in chapters 4 to 6. These particular chapters that deal with skeletal muscle, balance and articular cartilage, respectively, will include a specific introduction to the field, followed by the specific hypotheses, methods, results and discussion. The results presented in these chapters will be consolidated in the general discussion presented in chapter 7. 2 Background 3 2 Background 2.1 Microgravity and Ground Based Models 2.1.1 Microgravity Gravity is the force that affects all motion on earth and in space. In 1687, Sir Isaac Newton described for the first time the nature of gravity as the attraction of two masses towards each other. Gravitational force is defined as the product of the gravitational constant and the mass of an object. On earth, the constant acceleration, also called normal gravity is 9.81m/s² or 1g. It describes the acceleration of an object by gravity alone without any external influence. Gravity is the reason why we stand on the ground and why objects fall down. It is also the force that causes the Moon, satellites and also the International Space Station (ISS) to orbit Earth. Microgravitational conditions are the result of a free fall at the acceleration of 1G. The International Space Station orbits earth at a height of about 400 km where the gravitational field is still 88.8% of 1G. This is the force that is necessary to keep it orbiting around the Earth. The microgravity conditions on board the spacecraft are caused by the continuous free fall of the space craft around our Planet (Figure 2.1). Figure 2.1: Mechanism of microgravity caused by a free fall around Earth The International Space Station and all objects, including the astronauts inside it, fall at the same speed around Earth and this is perceived as “weightlessness”. The 2 Background 4 approximate speed that is necessary to create a free fall around Earth is 28.000 kilometers per hour. Since gravity is not zero but approximately 1x10-6 g we use the term microgravity rather than weightlessness. Microgravity can be created whenever an object is in free fall. Therefore, in addition to missions in space flight research with shuttles or the International Space Station, microgravity can also be associated with parabolic flights, sounding rockets or drop towers. Gravity plays a major role in our daily life on Earth. We are used to the fact that objects fall down and if we ‘lose’ something, we search the floor to find it. But how do you change your strategy searching a three dimensional space without the presence of normal gravity? While this reflects a major practical challenge, the human organism and its evolution have also been strongly influenced by gravity. When humans travel to space, the body rapidly adapts to the change in gravitational force. Motion Sickness and Puffy Face are two phenomena that can be observed very early during a space mission and this is followed by a huge number of adaptation processes in the human body that are caused by the lack of gravity. Generally, degradation of physiological processes and atrophy of several different tissues are observed. They reflect a natural adaptation to the microgravity environment which in turn can lead to health problems upon the return to the Earth environment. Since the early days of space flights, astronauts have been subjects for life science research with the aim to reduce the risks of space flight and to develop countermeasures in order to decrease the rate of degradation. 2.1.2 Ground Based Models As the number of subjects traveling to space is very limited, ground based models that simulate the effect of microgravity on the human body were developed in order to explore the response of the human body to immobilization and to develop adequate countermeasures. It is important to note that microgravity itself cannot be simulated except during free fall. During Parabolic Flights, time frames of approximately 30 seconds of microgravity can be achieved, which is too short to simulate physiological processes that occur during a space mission. Immobilization using bed rest has been shown to be a highly feasible model to simulate effects of microgravity on the musculoskeletal system. As described in the recent review: ‘From space to Earth: advances in human physiology from 20 years of bed rest studies.’ (Pavy-Le Traon et al., 2007), sitting on a chair or being 2 Background 5 immersed in water have also been used to simulate inactivity and the lack of gravitational forces. Water immersion is still used as a model in space flight studies because it can better simulate the lower gravitational forces acting on the human body than bed rest. However, water immersion studies involve a number of risks because the skin must be kept dry which creates a very complex experiment setting. The bed rest model has been generally accepted as the standard model for simulating the effects of microgravity for many physiological systems, particularly the musculoskeletal system. A bed rest model has been used by “Space Flight Nations“ for research purposes since the 1960’s. Russian researchers concluded from a study that bed rest at 6° head-down-tilt simulates more realistically the feeling to be in space (Kakurin et al., 1976; Pavy-Le Traon et al., 2007). Since that time 6°-head down tilt bed rest (6°-HDT bed rest) has been used to induce the effects of microgravity on the human organism and is now called the gold standard. However, ground based models can simulate only some of the physiological effects that occur under microgravity. Parts of the mechanisms that lead to these physiological effects may not be the same on the ground and in microgravity. Microgravity is a unique condition and a ground based model with its underlying assumptions can only try to replicate, as much as possible, the effects of spaceflight on the human organism. Bed rest studies can also be used to simulate physiological and pathophysiological adaptations of the human body due to a sedentary lifestyle, longer-term immobilization due to illness and/or injury or reduced mobility in aging. The advantage of bed rest studies is that they are conducted in a tightly controlled environment. In contrast to field studies, measures such as nutrient intake, fluid intake and exercise can be standardized and controlled making it possible to investigate the ‘isolated’ effect of unloading. 2 Background 2.2 6 Humans in Space – Physiological Effects 2.2.1 Physiological Effects of Microgravity The human body requires a certain amount of physical activity in a gravitational environment to maintain a healthy physical status of its various physiological systems. Changes in the demands on the human body can lead to physiological adaptations that enable the body to meet the new requirements. Athletes use this plasticity of the body’s “active” biological tissues, such as muscle mass, for instance by increasing the load during resistance training in order to achieve higher performance levels after several weeks of training. Space flight presents a complex challenge for the human body. The great variety of physiological adaptations of the human body due to the microgravity environment that affect, for instance, the musculoskeletal system, the cardio-vascular system, the immune system and fluid regulation can be observed during and after the astronauts’ stay in sapce. These adaptations of the body during a period in microgravity provide an excellent opportunity to investigate the impact of normal constant gravity on its physiological status (Convertino, 1996). Additionally, in terms of energy expenditure, the activity level in space is reduced when compared to daily life on earth. Particularly, since the use of the lower extremity is not necessary for locomotion, the accompanied reduction in energy expenditure should contribute to the major functional changes of the musculoskeletal system of the lower extremity. In the following, the effects of microgravity on different tissues and organs of the human body are described with a specific focus on skeletal muscle, balance and cartilage since these tissues and processes were investigated in this doctoral thesis. In general, the physiological effects are investigated under 1G conditions prior to the space mission and after returnning of the astronauts to Earth. The physiological changes caused by a microgravity environment normally do not harm the astronauts or limit them in their actions as long as they stay in microgravity. Also, they usually are not “pathological” in a space environment. However, once astronauts return to a gravitational environment, such as Earth (or Mars or Moon in the future), they may experience more or less serious health problems. While this may be of little concern when they return to Earth since they can receive adequate medical support, there could be major concerns regarding the astronauts’ safety during interplanetary missions. 2 Background 7 2.2.2 Skeletal Muscle Performance The skeletal muscles major tasks on earth are to facilitate the body’s upright position and enhance locomotion. The muscles move objects, for instance masses, against gravity. In microgravity, this force is lacking which means a reduced effort for locomotion and consequently leads to disuse induced atrophic processes in skeletal muscles. As a response to the change of demands by microgravity, there is a physiological adaptation of muscle in terms of structure as well as function. The so called anti-gravity muscles of the lower extremity are mainly affected by microgravity since the difference in load for these muscles is greater than for arm and trunk muscles. Decreased muscular performance limits their physical activity for a certain period of time once they return to a gravity environment such as Earth or Mars. Loss of strength has been measured for different muscle groups of the body in microgravity (Kakurin et al., 1976; Kozlovskaya et al., 1981; Thorton and Rummel, 1977) and it affects both maximum strength and power. Thorton et al. (1977) concluded that microgravity reduced muscle strength primarily in the lower extremity. They further stated that the rate of loss in muscle strength was directly linked to a reduction of body weight and leg muscle volume during the flight and was inversely related to the amount of in-flight training performed by the astronauts. When analyzing space flight results it has to be taken into account, that for example NASA flight rules require that crew members must exercise if the flight duration is longer than 10 days (Adams et al., 2003). This would lead to an underestimation of the actual effects that microgravity alone would have on skeletal muscle. In addition, discrepancies between the results of, for instance, Russian and American Missions could be partly explained by these different rules. To date, it is not known whether the high variability of microgravity effects between astronauts is caused by different in-flight countermeasure treatments or is a true difference in the sensitivity of skeletal muscle to microgravity (Fitts et al., 2000; Fitts et al., 2001; Lambertz et al., 2001; Zange et al., 1997). Further, it is acknowledged that data collected during space flight are rare and that the level of control of factors including, for instance pre-flight training level, in-flight training intensity or nutrition, is limited. Usually, the primary aim of space missions is not to conduct a physiological study. Rather, in the past, physiological studies were often performed as a side product because of the scarcity of ‘free time’. Further, the motivation and opportunity to exercise during a mission differ between astronauts and missions. During space flight, no comparable atrophic effects could be investigated for the arm muscles. 2 Background 8 This may be due to the fact that, first of all, astronauts use the arms in microgravity for locomotion inside the shuttle or space station and also when they perform experiments during the flight. Secondly, the differences in requirements in 1G conditions compared to microgravity conditions are not as pronounced for the arms which may result in less muscle atrophy. This might also indicate the impact of the pre flight activity levels on the adaptation of skeletal muscles to the microgravity environment. The specific background in chapter 4 -Muscle Performance – will provide more details on changes in skeletal muscle due to microgravity. 2.2.3 Balance During spaceflight, the demands on the lower extremity muscles are reduced to a minimum which not only leads to changes in muscle performance but also affects the ability to stabilize body position when astronauts return to Earth. Peripheral and central neural processes of postural control are physiologically and functionally altered when astronauts return from a stay in microgravity (Clement et al., 2005). Although postural control is important for the operational performance during a space mission, the focus of this study will be on changes in postural body control after a period of immobilization which is comparable to the return of astronauts into a gravity environment, such as Earth, the Moon or Mars. Astronauts then show a reduced ability for postural control together with less muscle performance which can pose a major safety problem or risk of injury. This is especially important for future interplanetary missions, where astronauts cannot always rely on physical support from team members on Earth. Consequently, the effects of microgravity on balance should be assessed and appropriate countermeasures should be considered in order to minimize these safety issues and risks of injury. Details of the effects of microgravity on balance will be introduced in chapter 5 Balance. 2.2.4 Cartilage Articular cartilage in synovial joints serves a variety of functions, including providing joint congruency, transferring and distributing forces, and allowing joint movement. A healthy biological and mechanical environment of cartilage is the prerequisite for proper joint function. Cartilage, like other biological tissues including skeletal muscle and bone, is sensitive to loading and disuse (Johnson, 1998; Smith et al., 1992a). 2 Background 9 Typically, a change in the biological and/or mechanical environment of cartilage leads to cartilage degeneration or osteoarthritis. While the role of mechanobiological factors for healthy cartilage development and maintenance have received much attention (Carter and Wong, 1988a; Wong et al., 1999; Wong and Carter, 1988) the effects of space flight or immobilization and partial weight bearing after injuries on cartilage biology and morphology in man are largely unknown. Some animal studies (Haapala et al., 2000; Jurvelin et al., 1986; Kiviranta et al., 1988a) have shown decreases in cartilage thickness and cartilage stiffness in dogs after 11 week of immobilization whereas other studies found no changes in proteoglycan and collagen content, cartilage stiffness or cartilage thickness (Setton et al., 1997) after immobilization of canines. The discrepancy of these results may be due to the fact that the type of immobilization plays a role in the potential of the cartilage to recover (Behrens et al., 1989) .Only few studies (Eckstein et al., 2000; Eckstein et al., 2002a; Eckstein et al., 2002b; Eckstein et al., 2005; Helminen et al., 2000; Hinterwimmer et al., 2004; Hudelmaier et al., 2003; Muhlbauer et al., 2000; Vanwanseele et al., 2002; Vanwanseele et al., 2003) have investigated the influence of unloading on articular cartilage in humans so far. Studies on human articular cartilage in the scope of space flight research have, to the best of our knowledge, not been performed so far. Specific details on the sensitivity of articular cartilage and biomarkers of cartilage health will be given in chapter 6 -Cartilage Health. 2 Background 2.3 10 Vibration Training Scientists have investigated the effects of vibration on the human body for many years. Most frequently, vibrations were studied in the context of occupational medicine and considered as ‘negative’. For instance, by damping seats in trucks and cars, health risks potentially arising from vibration have been minimized. The potential danger of the application of vibrations to the human body can not be neglected and will be discussed in chapter 2.5. Nevertheless, in the past decade, vibration training has become very popular as a complement to regular strength training (Jordan et al., 2005) in an attempt to increase the efficiency of strength training that may affect all tissues of the musculoskeletal system. Current research is conducted to find the optimal combination of different variables such as training intensity, frequency and amplitude of the vibration, mechanical characteristics of the vibration input and others that would result in a positive response in terms of an anabolic reaction in training processes. An increasing number of studies investigating the effects of vibration are being published each year and the results describing all facets of vibration training, most frequently the effect on muscular performance, have been published in various reviews (Cardinale and Wakeling, 2005; Issurin, 2005; Jordan et al., 2005; Luo et al., 2005; Mester et al., 1999b; Mester et al., 2001; Mester et al., 2006; Nordlund and Thorstensson, 2007; Rehn et al., 2007). This chapter will deal with the physics of vibration and the human body, followed by the known effects of vibration training on the musculoskeletal system, possible underlying physiological mechanisms and health risks. 2.3.1 Physics of Vibration Vibration has been defined as the motion of a particle which oscillates about its position of equilibrium (Beer and Johnston, 1987). Vibrations can be divided into deterministic and stochastic vibrations and can be classified as shown in Figure 2.2. Only with a sinusoidal vibration is it possible to study the response to a single frequency of motion (Griffin, 1996). Consequently, studies on the human response to vibrations usually use the reactions to pure sinusoidal vibrations. Vibration studies investigating vibration exposures of people during work, travel or leisure are often described as random vibrations. 2 Background 11 Figure 2.2: Classification of Vibrations of different types of oscillatory motion (Griffin, 1996) Vibrations can be described by the parameters of amplitude, frequency and magnitude. The amplitude of the displacement of the vibration is determined by the extent of the oscillation and the frequency by the repetition rate of the cycles of the oscillation. The measure for frequency is cycles per second (s.p.s.) and the unit is ‘Hertz’ (Hz). The simplest type of motion contains only one frequency and would 2 Background 12 occur when there is a sinusoidal oscillation at only one frequency. Normally, the human body is exposed to more than one frequency. The response to vibration exposure is highly dependent on the frequency content of the vibration. The magnitude of the displacement of oscillatory movements can be measured in many different ways. First, it can be described as the difference between the maximum displacement in one direction and the maximum displacement in the opposite direction. However, displacement is only useful to describe large-amplitude and low frequency vibrations. Secondly, the magnitude of the oscillation can also be described by its velocity; a quantity that is related to the energy of the vibration. Thirdly, the magnitude of oscillations can be described by its acceleration. The acceleration is expressed in meters per second per second (m/s ² or m*s-²) (Griffin, 1996). 2.3.2 Mechanical Properties of the Human Body Knowledge of the mechanical properties of the human body is important when investigating the effects of vibrations. They help to estimate the physiological and pathological effects that can be expected when the body is exposed to vibrations. Knowing the mechanical properties also allows the biomechanical interpretation of physiological responses caused by vibrations (Hauptverband der gewerblichen Berufsgenossenschaften (Edt.), 1984). The human body can be described as a damped-free-vibrating system and the model that is usually used is a spring-mass-model. However, the human body is a system with many different tissue properties which lead to different spring constants and damping properties (i.e. muscles, ligaments, tendons, fat tissue bones and others). Other variables, such as the masses of bones and other tissues, are difficult to measure and may change due to different muscle activity (Hauptverband der gew. BG (1984); (Rasmussen, 1983)). 2.3.3 Classification of Vibration Training In the past decade, vibration training has evolved into a well known and wide spread training method. The use of vibrations in isometric strength training was first developed in Russia where training devices were used to transmit vibrations to the muscle belly (Cardinale and Wakeling, 2005; Nazarov and Spivak, 1985). However, the physiological consequences of vibration training are not fully understood. Although very little is known about the mechanisms on how vibration training 2 Background 13 stimulates the human body, the manufacturer of the various commercially available training devices (e.g. Galileo 2000 or Powerplate) have been advertising and selling their machines. When reviewing the literature on vibration training and on the influence of vibrations on the human body, one should distinguish between whole body vibration training and vibrations applied directly to the muscle belly or tendon. With regard to the human body, the vibrations can be classified according to the point of contact with the human body and on the proportion of the body they affect. The different modes of vibration training range from whole body vibrations to local or regional vibrations and can be foot-transmitted, head-transmitted or hand-transmitted vibrations. Further, whole body vibration can be transmitted to the body while sitting, standing or lying on the vibrating surface (Griffin, 1996). In sports, the body experiences various types of vibration such as during alpine skiing, inline skating or cycling. Where the body receives the vibration and whether it is possible for it to damp the vibrations or not, determines if they are “good” or “bad” vibrations. More about safety considerations and criteria for “good” and “bad” will be discussed in chapter 2.4 Health Risks. The fact that the body is comprised of many different tissues makes the system more complex and adds to the difficulty in understanding the response of the body to vibrations (Spitzenpfeil et al., 2000). Vibrations can also be classified by the type of oscillation produced by different vibration devices. During whole body vibration training, the subject or athlete usually stands on a vibration platform that produces oscillation vibrations. Depending on the position of the subject on the plate, the vibrations are transmitted through the whole body and even the head can receive a great amount of the mechanical vibration signal, which must be regarded as one of the most dangerous effects. The vibration plates that are currently available on the market produce two main types of signals: a. alternate acceleration of the left and right leg like a seesaw b. simultaneous vibration of the whole body So far there is no evidence, that one plate elicits better training responses than the other although the different companies say so. Many different companies offer their latest development of vibration plate such as for example: - the Nemes Bosco System®, OMP, Rieti, Italy; 2 Background - 14 Galileo 2000® device and Space Galieleo®, Novotec Pfortzheim, Germany, - Powerplate® North America Inc., Northbrook, IL, USA, - VibroGym® , ES Haarlem, The Netherlands Not only the characteristics of vibration as an input signal can be classified but also the effect vibration elicits in the human body. The effects of vibrations on the human body can be divided into ‘mechanical effects’ and ‘biological effects’. Mechanical effects describe the resonance and damping properties of the human body. Biological effects deal with the respiratory, cardiovascular and neuro-muscular effects of vibration on the human body (Cole, 1982). However, in practical applications it will be difficult to distinguish between the two as it is not possible to apply vibration to a living organ and only elicit biological or mechanical effects. Additionally, Griffin (1996) defines effects on comfort, physical activity and health of the person. The following chapters however, will deal with the biological adaptation of the body to vibration training. 2.3.4 Biological Adaptation to Vibration Training 2.3.4.1 Neurophysiological Effects Although there is increasing interest in vibration training as a tool for rehabilitation, training or prevention, knowledge about the physiological processes that vibration training elicits is still limited. This is mainly due to the very complex input signal caused by the vibration and the complexity of the human/animal body. Usually, investigator groups are not able to account for all possible effects generated by vibration. Consequently, each study only gives limited insight into the actual effect vibration may have on the body. In most of the studies investigating the training effects of vibration training, neural adaptations to the vibration stimulus are expected. If a muscle is vibrated, this stimulates the primary endings of the muscle spindle which consequently excites the α-motoneurons and leads to muscle contraction. This tonic contraction of the muscle has been described by Eklund and Hagbarth (Eklund and Hagbarth, 1966) as the tonic vibration reflex (TVR). In their experiments they applied high frequency vibrations directly onto the tendon which led to a contraction of muscle and the relaxation of the antagonist (Eklund and Hagbarth, 1966; Mester et al., 2001). However, the involvement of the tonic vibration reflex during vibration training has 2 Background 15 not yet been experimentally proven and it has not been shown how such a mechanism would cause a positive effect on muscle performance (Mester et al., 2001; Nordlund and Thorstensson, 2007). The tonic vibration reflex can actively be influenced by higher cortical centers of motor control and it has not yet been shown whether mono-synaptic or polysynaptic pathways are dominantly used for signal transmission through the body (Mester et al., 2001). Usually, in whole body vibration training, the mechanical input is applied through the feet and other receptors than the muscle spindles are also stimulated such as for example the Golgi-tendon organs. In the experiments of Eklund and Hagbarth (1966), only the tendon was stimulated; whereas in vibration training, both the tendons and muscle are likely to be stimulated through vibration. Thus, there may very well be an overlap of several mechanisms that stimulate various receptors. Nordlund et al. (Nordlund and Thorstensson, 2007) criticize the use of the tonic vibration reflex as an explanation for the positive findings of vibration training. First they state, that the tonic vibration reflex was demonstrated in a very different setting from vibration training since the time of exposure was only 30s and the frequency was higher than normally used in vibration training. Also, they put forth the criticism that later experiments where vibration was directly applied to the muscle and a decrease in muscle activity was reported (Bongiovanni et al., 1990; Ribot-Ciscar et al., 1998) are often not considered in the discussion about the effects of vibration training. Additionally, they noted that muscle spindle firing also causes inhibition of the antagonistic muscles via reciprocal inhibition (Crone and Nielsen, 1994) and thus a prediction of the actual activation level during the exposure to vibration would be difficult (Nordlund and Thorstensson, 2007). They suggested that for an assumed increased level of muscle activation during whole body vibration, the training would have to cause an increase in the ability to maximally activate the agonistic muscle and/or to improve inter-muscular coordination (e.g., decrease the activation of the antagonistic muscles). Nordlund et al. (2007) also questioned the theoretical benefits of whole body vibration training on coordinative performance as, from their perspective, the training method lacks specificity. They concluded that there was no evidence for justifying a recommendation of whole body vibration as a replacement or addition for strength training. 2 Background 2.3.4.2 16 Muscle Performance The term muscle performance comprises a wide range of parameters that can be measured. The parameters one can measure in the context of skeletal muscle performance are as diverse as the studies that have been published on the effects of vibration training. During whole body vibration training, the subject performs isometric or dynamic exercises on a vibrating platform. In addition, the regular parameters such as intensity, repetitions and amount of series of a specific exercise, training protocols for vibration training can be adjusted in frequency and amplitude. Various vibration frequencies between 15 Hz and 90 Hz have been used to achieve adaptations in skeletal muscle or bone (Issurin, 2005; Rubin et al., 2002a). For safety reasons (see also chapter 2.4), it has been suggested to exercise only on the vibration plate with flexed knees, as this position minimizes the transmission of vibrations to the head (Cardinale and Rittweger, 2006). One can either measure the acute effects of vibration training, i.e., during or right after the application of the training, or the long-term effects. However, there is no clear-cut definition what is “acute” or “short-term” and what is “long-term”. The results after two weeks of vibration training can be considered long term when compared to measurements taken after a single bout of vibration. On the other hand, the results after two weeks can be taken as acute or short-term effects when compared to a six month vibration training intervention. Regardless whether acute or long term effects were studied, the published results have so far been controversial. Torvinen et al. for instance showed an increased jump height and isometric knee force (Torvinen et al., 2002a) after 4 minutes of vibration training. Other studies looking at the acute effects of vibration training found a decline in muscular performance (De Ruiter et al., 2003; Torvinen et al., 2002a). Studies on long-term effects of vibration training revealed that vibration training could be beneficial for muscle performance. Several studies showed positive training effects on muscle strength and power (Issurin et al., 1994; Issurin and Tenenbaum, 1999; Liebermann and Issurin, 1997; Mester et al., 1999a). Increased performance after the exposure to whole body vibration could be the result of an improved synchronization of motor units and an improved co-contraction of the synergistic muscles (Haleva, 2005; Jordan et al., 2005). More details on the effect of vibration training on muscle performance will be presented in chapter 4 - Muscle Performance. 2 Background 2.3.4.3 17 Balance Since the application of vibrations to the human body activates the neuro-muscular system (Haas et al., 2004), it should also influence the coordination of movement. Without affecting the coordinative portion of movement, vibration training would not be able to enhance muscle performance. Additionally, there are certain receptors, especially in the cutaneous tissue, that sense vibratory movements and hence certainly will be affected by vibration training (for more details see chapter 5.1.1). Studies on the effects of vibration training or vibration stimuli on balance and coordinative processes have been performed mostly in medical environments. Such examples as in the context of rehabilitation of orthopedic injuries (Berschin and Sommer, 2004) and the prevention of fall risk (Bautmans et al., 2005; Bruyere et al., 2005; Kawanabe et al., 2007) have produced promissing results. Also, vibration training becomes popular as a training method for the treatment of neurological diseases such as Parkinson disease (Haas et al., 2004; Turbanski et al., 2005) or Multiple Sclerosis (Schuhfried et al., 2005) and injuries resulting in paraplegic patients (Melchiorri et al., 2007). More details on the effect of vibration training on balance performance will be presented in chapter 5 - Balance. 2.3.4.4 Cardio-Vascular-System Since the cardio-vascular system serves as a ‘supplier’ for muscle and bone it should also be affected as soon as vibration training affects the human body. Additionally the vascular system that is close to the source of vibration should be affected from the mechanical input signal since the vessels are vibrated as well with the rest of the body. Therefore, this chapter will deal with the effects of training on the cardio-vascular-system on the one hand and with direct effects on the vessels on the other hand. 2.3.4.4.1 Endurance Performance Rittweger et al. (Rittweger et al., 2000) showed an oxygen uptake of less then 50% of VO2 max during cycle ergometry when performing whole body vibration training to exhaustion. Additionally, systolic arterial blood pressure increased after vibration training whereas diastolic blood pressure decreased. The reason for the decrease in diastolic blood pressure could have been arterial vasodilatation that could be accounted for by changes in muscular perfusion. They suggested that exhaustive whole body vibration elicits only a mild cardio vascular exertion and that neural as 2 Background 18 well as muscular mechanisms may play a role in the functioning of vibration training. Also vibration training led to erythema, swelling or itching in some subjects (Rittweger et al., 2000) which might have been caused by an increased cutaneous blood flow (Cardinale and Rittweger, 2006). Overall, the observed very mild cardiovascular effect led them to conclude that this training method was well applicable in the elderly as it did not stress them into exhaustion. In a study by Kerschan-Schindl (Kerschan-Schindl et al., 2001), it was shown that muscle blood volume increased in the calf and thigh during whole body vibration training at 26Hz. In their study, blood pressure did not change with vibration training. As previous studies have produced contradictory results at much higher frequencies (Lundström&Burström 1984, Bovenzi&Griffin 1997), the authors concluded that the circulatory response was highly dependent on the magnitude as well as the vibration frequency. Also, the group showed an increase in blood flow in the popliteal artery suggesting that vibration training reduced the viscosity of blood and thus increased it’s velocity through the arteries. More recent studies published by Rittweger (Rittweger et al., 2001; Rittweger et al., 2002) showed that the metabolic power of skeletal muscle was enhanced during vibration training and could be controlled by frequency and amplitude of the vibration, as well as by the application of additional loads. Cardinale et al. (Cardinale and Wakeling, 2005) suggested that the above mentioned studies indicated a mild effect of vibration training on the cardiovascular system. However, they concluded that the stimulus of whole body vibration would be too low making it unlikely that athletes would benefit from it as a new training method. However, it has to be taken into account that the training design choosen by Rittweger and Kerschan-Schindl was not used to enhance endurance performance. Adding whole body vibration on a cycle ergometer or on a treadmill may produce better results for the cardio-vascular system. Suhr et al. (Suhr et al., 2007) could show, for example, that high intensity cycling under vibration conditions could enhance the concentration of vascular endothelial growth factor (VEGF). The results suggested a positive effect of vibration training on the angiogenesis. 2.3.4.4.2 Energy Expenditure Only a few studies addressed the effect of vibration training on energy expenditure of vibration training. Rittweger et al. (2002) reported that metabolic power increased with vibration training. They stated after VO2max measurements with and without vibration that energy requirements during vibration training were as high as during 2 Background 19 moderate walking and that this could even be increased with increasing frequency and amplitude of the vibration signal (Rittweger et al., 2002). Da Silva et al. (Da Silva et al., 2007) investigated the effects of vibration training used for hypertrophy training on energy expenditure. They found that application of vibration training during half squatting increased energy expenditure when compared to non-vibration controls. 2.3.4.4.3 Mechanical Effects on the Cardio-Vascular-System Studies on cardiovascular effects of vibration training are rather scarce to date. Most of them are done on animal models. Murfee et al. (Murfee et al., 2005) found that 6 weeks of vibration training for 15 minutes/day stimulated vascular remodeling in mice, meaning they observed a decrease of blood vessels per muscle fiber in mouse soleus muscle while the muscle fibers themselves and the number of muscle fibers did not change. They were surprised at the results since they were not as expected. However, the authors pointed out that the vascular remodeling was sensitive to the applied vibration protocol and the direction of the response could have been altered to an anabolic response with changing the training intensity. Yue et al. (Yue and Mester, 2007a; Yue and Mester, 2007b) performed a model analysis to predict the effects of whole body vibration on the cardiovascular system and more specifically, the blood vessels in humans. Hydrodynamic analysis showed that longitudinal vibration of vessels increased the shear stress on the vessel walls, especially in the larger vessels such as the aorta, larger veins and arteries, and the coronary artery. They suggested, that this strong mechanical stimulus could be beneficial because it might elicit endothelial-dependent and nitric oxide-dependent angiogenesis (Yue and Mester, 2007a). On the other hand, the increased shear stress could be a potential risk factor when performing vibration training with a history of diseased coronary or cerebral arteries. The lateral component of the vibration signal was analysed separately and showed that vibration led to a dilation of the vessel which significantly decreased the total peripheral resistance (Yue and Mester, 2007b). The mechanisms underlying that finding seemed to be mechanobiological in nature. The vibration causes motion of the red blood cells which, in turn, causes them to collide with the walls of the vessels and with each another. These collisions may induce the release of nitric oxide (NO), a strong vasodilator. The authors suggested, that vibration training may have been beneficial to improve the ability of the body to counteract high blood pressures with the vasodilatation (Yue 2 Background 20 and Mester, 2007b). Similar results were published by Mester et al. (Mester et al., 2006) who found an increase in peripheral resistance during vibration training at different frequencies compared to pre-training levels. However, after exercise, the peripheral resistance was lower than the pre-training levels which suggested that the body compensated for the higher oxygen requirements during training by dilating the vessels (Mester et al., 2006). Although the number of studies dealing with the direct effects off vibration training on the vascular system is small, as opposed to the effects on endurance performance, the results are similar. The vascular system of the body is sensitive to even very low mechanical stimulation. 2.3.4.5 Endocrine System The effect of vibration training on the endocrine system has not been studied in depth yet. However, some studies in the past years have investigated acute and long term effects of vibration training on the endocrine system (Cardinale et al., 2006; Di Loreto et al., 2004; Kvorning et al., 2006b). It has been stated that the additional gravitational load the subject is exposed to elicits an anabolic hormonal response (Cardinale and Bosco, 2003). This would be comparable to mechanistic studies during conventional strength training where evidence evolved that increasing blood levels of anabolic hormones are positively correlated to both muscle hypertrophy and muscle strength (Ahtiainen et al., 2003; Kraemer et al., 2002; Kraemer and Ratamess, 2005). Some studies have investigated the acute effect of vibration training on the endocrine system (Bosco et al., 2000b; Bosco et al., 2000a; Cardinale et al., 2006; Cardinale and Bosco, 2003; Kvorning et al., 2006a). Bosco et al. (2000) applied 10 minutes of whole body vibration at 26 Hz and 4 mm amplitude to recreationally active people (Bosco et al., 2000b). They reported acute increases in serum levels of testosterone and human growth hormone (hGH) and decreases of cortisol levels. However, as stated by Cardinale et al., their earlier study was missing a control group; thus, the differences between conventional resistance training and whole body vibration training remains unknown (Cardinale and Wakeling, 2005). Recent studies used better control conditions. Di Loreto and Co-Workers (Di Loreto et al., 2004) hypothesized that vibration training might be a treatment for obesity because increasing serum levels of hGH and testosterone and concurrent inhibition of cortisol should have lead to a reduction of fat and augmentation of lean body 2 Background 21 mass; thus reducing fat mass. In order to test their hypothesis they exposed 10 healthy men to 10 x 1 minute of whole body vibration training at 30Hz and investigated the effect on circulating levels of glucose, insulin, glucagon, hGH, IGF-1 cortisol, epinephrine, norepinephrine and total and free testosterone. However, their hypothesis could not be confirmed. Although they found slightly reduced plasma glucose and slightly increased plasma norepinephrine levels, all the other parameters remained unchanged. Therfore, they concluded that vibration training transiently reduces plasma glucose, possibly by increasing glucose utilization by contracting muscle, and increases plasma norepinephrine, possibly by protracted peripheral sympathetic pathway activation (Di Loreto et al., 2004). They suggested that the hormonal response of vibration training is not mediating the anabolic effects of vibration training on bone and muscle. However, it has to be acknowledged that the intensity of the applied training may not have been high enough as subjects only stood on the vibration plate and performed a static exercise without additional load. Kvorning et al. (Kvorning et al., 2006a) reported greater increases in cortisol when performing squats with vibration than squats alone. Combining conventional resistance training (squats) with vibration did not increase testosterone levels; however, it did stimulate a greater response in hGH in the first training. Changes in hGH and testosterone were similar when squats were performed on a vibration plate and squats alone. Their decision to generally reject the hypothesis that whole body vibration training could optimize resistance training and the anabolic hormonal response to it should be modified in that way that the training protocol they used did not lead to beneficial effects on the hormonal response to resistance exercise. This is important to note as there is potential to optimize the time point of testing and measuring as well as the training intensity itself. Also, the most recent studies on the anabolic stimulation through vibration training (Cardinale et al., 2006; Erskine et al., 2007) did not find an increase in testosterone and IGF-1 levels. They tested the effect of a single session of vibration training on the hormonal response. In summary, the hormonal response to vibration training on a systemic level did not show consistent results yet. Similar to many of the other physiological systems of the human body, the training intensity has to be tailored much more individually than it has been done to date and it seems that often intensity levels for the vibration condition were very often not high enough for the chosen sample of test subjects. 2 Background 2.3.4.6 22 General Performance To summarize the training effects of vibration training, it is concluded that there is still no consensus on how vibration training “works” and whether it is a beneficial method to amend traditional training methods. It appears that there is a lack of systematic research in the area. Most of the studies are in terms of training intensity and volume not tailored to any specific training method. For example if the training includes squats with additional weight there is a training impact on the quadriceps muscle. However, to find changes in calf muscle performance or in endurance parameters after that kind of training is unlikely. Therefore, in future studies, the training protocols should be much more tailored to the muscle or focused on the system of interest. Jordan et al. (Jordan et al., 2005) stated that the variability in outcomes of vibration studies may be a result of the differences in the training protocols. Most of the protocols used thus far, vary in vibration characteristics, position on the plate, performed exercise on the plate, additional load and others. It is probable that each of these parameters affects the physiological response to the applied training. Consequently, there is a need for well controlled studies to explore further the effects of vibration training. 2 Background 2.4 23 Health Risks The human body consists of rigid structures, such as bones, and non-rigid structures such as muscles, fat tissue and other soft tissues such as organs. Every structure, including biological tissues has resonance frequencies. If a structure is hit by its resonance frequency this can lead to destruction, not only for example for bridges but also for tissues. Therefore, vibration exposure is an important issue in the field of occupational medicine as vibrations often occur in the working environment (e.g., car seats, jackhammer, chain saw) and can cause discomfort, injury and disease (Griffin, 2004). The resonance frequency (natural frequency) varies depending on the mechanical properties of the structure in question. Bones have resonance frequencies of 200 to 900 Hz (Nigg and Wakeling, 2001) and the resonance frequency of different muscles ranges between 5 and 65 Hz (Wakeling and Nigg, 2001). If the vibrations transmitted to the human body overlap with the resonance frequency of the specific tissue, there may be pathological effects. If the body is exposed to long-term or high-energy vibrations, this often results in discomfort or even pathological changes to the nervous and vascular systems (Sakakibara, 1994). The resonance frequencies for different extremities, including the organs, are presented in Figure 2.3. Resonance frequencies depend on the posture of the person when receiving vibrations as they change with muscle activity (Wakeling and Nigg, 2001). How exposure to the vibrations can be tolerated also depends on the direction in which the vibrations act on the human body. The resonance frequencies of muscle are in the range of the input frequencies the body receives; for example, during the landing in sport activities such as normal running (Stefanyshyn and Nigg, 2000). Due to the structural composition of the human body it is difficult to observe how the vibrations are transmitted through the body (Junghans, 1986) and how they change from the time when they are introduced to the body to the time they are damped out. Also, the various joints increase the variability of the transmission of the vibrations through the human body. Additionally, the health risk of vibration training is dependent on the characteristics of the stimulus itself (Cardinale and Rittweger, 2006). Hand-transmitted vibrations can cause the so called hand-arm-vibration syndrome experienced by workers using vibration equipment such as jackhammers whereas long exposure to whole body vibration in an industrial setting can cause lower back pain (Cardinale and Pope, 2 Background 24 2003). Lower back pain is a very good example of the importance for the right dose of vibration training as it can be beneficial for the prevention of lower back pain if the training occurs in small doses. Figure 2.3: Resonance frequencies of different tissues of the human body (Mester et al., 2001). It is noted that there is no ‘recipe’ for the right dose of vibration in order to be beneficial. As Cardinale et al. (2006) pointed out, the frequently used protocol of 10 minutes vibration training at 2 mm amplitude is above the limits of vibration exposure for workers in the European Union (The European Parliament and the Council of the European Union, 2002). However, it may be beneficial in regimented training. Also other protocols that are reasonable in vibration training are well above the “caution zones” (Figure 2.4) defined for workers (ISO 2631-1, 1997). 2 Background 25 Figure 2.4: “Caution zones” as defined in the ISO 2631-1 (ISO 2631-1, 1997) compared with the vibration exposure in previously used vibration training protocol. When using vibration training, one has to keep in mind the danger of the chosen method. Each participant will show a different response to this type of training; thus training protocols should be designed individually. Also, the body should be given the opportunity to damp the occurring vibration. Consequently, participants, for example, should never extend their legs fully nor should they sit on the platform as this limits the ability of the body to respond to the vibration stimulus. 2 Background 2.5 26 General Hypotheses In summary, research publications have shown in the past decade that vibration training has become a very popular complement in exercise programs and positive effects on various musculo-skeletal-systems have been reported. Vibration training mainly addresses increases in muscle performance and bone mass as well as an enhanced ability to stabilize body position. Joining the potential of vibration training and the atrophic processes in humans observed during a sojourn in microgravity, there seems to be a potential countermeasure. However, to date, the literature in the field of vibration training is still very controversial and there seems to be a lack of systematic research which had been proposed by other previous authors (Cardinale and Wakeling, 2005; Jordan et al., 2005; Nordlund and Thorstensson, 2007). There is a wide range of vibration training protocols being used and also a wide range of experiments that have been applied either during or after the application of vibration training. Infrequently a whole set of measures has been applied to the same population of subjects and even less frequently, different tissues have been investigated in the same study campaign. Consequently, the general purpose of the Vibration-Bed-Rest-Study (VBR-Study) was to investigate the effects of 14-days of a 6°-head down tilt bed rest (HDT bed rest) on the human body in an integrative approach, including skeletal muscle, bone, knee cartilage, hemodynamics, balance performance and the cardiovascular system, and to determine whether vibration training can counteract the effects of immobilization on these systems. The general hypotheses were: a) 14-days of HDT bed rest lead to a general deconditioning of the human body. b) Vibration training has the potential to counteract deconditioning during 14-days of HDT bed rest in terms of slowing down or preventing the effects on the human body. To test these hypotheses, a total of 10 experiments have been conducted during the VBR-Study, each consisting of multiple measurements. Additionally, blood, urine and feces samples were taken on all days, as indicated in Table 2.1, in order to analyze markers of bone and cartilage metabolism, calcium excretion and 2 Background 27 endocrinology of muscle metabolism, cardio-vascular function and hemodynamics. When establishing the study schedule, a crossover design was chosen and it was ensured that the different experiments did not impact each other. The order of the experiments was identical for the two phases of the study. In this thesis the results of the following experiments will be presented and discussed: o Skeletal Muscle Performance (Chapter 4) o Balance Performance (Chapter 5) o Cartilage Biology and Morphology (Chapter 6) 2 Background 28 Table 2.1: Overview of the experiments conducted in the VBR-Study. Abbreviations: MRI = ‘Magnet Resonance Imaging’, MRS = ‘Magnet Resonance Spectroscopy’. Subjects experienced HDT bed rest during the intervention period. 3 General Methods 29 3 General Methods 3.1 Study Design The Vibration-Bed-Rest-Study (VBR Study) was carried out in August / September 2004 and February / March 2005 in a randomized cross-over-design. Subjects performed two study phases: one containing the control intervention, the other containing the vibration training intervention. Each of the two study phases consisted of 23 days during which the subjects remained stationary in the clinical research center of the Institute of Aerospace Medicine in the German Aerospace Center (DLR), in Cologne, Germany. Each study phase was divided into three periods: a 4-day adaptation period, a 14-day intervention period with bed rest in a 6°-head down tilt (HDT) and a 5-day recovery period (see Table 3.1). Table 3.1: Study design of the VBR-Study. HDT is the abbreviation for Head-Down-Tilt (HDT). Study Phase Adaptation normal A physical activity (4 days) normal B physical activity (4 days) Intervention 6°-HDT bed rest + vibration training (14 days) 6°-HDT bed rest + control (14 days) Recovery normal physical activity (5 days) normal physical activity (5 days) Both study phases were identical with respect to environmental conditions, study protocol and diet. How these measures were standardized will be described later in this chapter. The subjects were randomly divided into two groups. All subjects completed both study phases and the order of the study phases was randomized. Subjects were allowed to walk around inside the clinical research center during the adaptation period and the recovery period; however, physical exercise was not allowed. 3 General Methods 30 During the intervention periods, subjects were kept in bed for 24h every day at a 6°head down tilt bed rest (HDT bed rest) and were not allowed to elevate their upper body. All activities, including eating, showering, and weighing, were carried out in the 6°-HDT position. In the clinical research center, controlled daylight exposure, constant room temperature and relative humidity were ensured. During the intervention period, subjects either received vibration training or the control intervention. 3 General Methods 3.2 31 Study Location The clinical research center is located in the basement of the building of the Institute of Aerospace Medicine, DLR, Cologne, Germany. It contains 8 single rooms for the subject accommodation and two bathrooms in the sleeping area and kitchen, living room, bathroom and 4 rooms for experiments or storage in the living area. Figure 3.1: Floor plan for the clinical research centre at the DLR-Institute of Aerospace Medicine, Cologne, Germany. 3.3 Population 3.3.1 Recruitment Process For subject recruitment, several media were used for advertisement in order to get a high number of applicants. Criteria for subject selection included: - a healthy male, - age between 18 and 35 years, - bodyweight: 75 ± 10 kg, - height: 180 ± 10 cm, - willingness to participate in the complete study, including both study phases, - ability to pass a screening test for sinistrin-hypersensitivity. Criteria for exclusion of the study: - regular physical training (more than 3 x per week), 3 General Methods - 32 drug, alcohol and substance abuse (e.g. regular consumption of more than 20 – 30 g alcohol / day), - adiposity / underweight, - smoking, - increased risk of thrombosis. Using a telephone screening questionnaire, the first selection, following the established criteria, was conducted. Potential subjects then received a detailed subject information brochure and were invited to an information seminar presented by the head medical doctor and the study coordinator. If the applicants remained interested in performing the VBR-study, they were asked to complete a psychological screening questionnaire. Due to the high demands of the study protocol for the subjects, these tests were highly relevant as they gave information about the personality of the candidates and whether they were aware of and understood their responsibilities if they participated in the study and had the potential to ‘work’ in a team. The psychological questionnaires were administered and evaluated by the aviation and space psychologists of the DLR-Institute of Aerospace Medicine in Hamburg, Germany. The final selection of the subjects was done using the following criteria: a) the results of a medical screening at the Aeromedical Center of the DLRInstitute of Aerospace Medicine in Cologne, Germany, which was done by an independent physician, b) the content of the individual psychological interviews which were performed by the aviation and space psychologists of the DLR-Institute of Aerospace Medicine, the study coordinator and the head physician of the study. This highly complex screening process was necessary to minimize the risk of subjects for droping out of the study. Since the study is very complex, a drop out could not have been replaced and had jeopardized the statistical analysis. 3.3.2 Subjects Eight healthy male subjects (average ± 1 standard deviation; age: 26 ± 5 years; mass: 78 ± 10 kg; height: 179 ± 10 cm) participated in this study after giving their informed consent in accordance with the approval of the Ethics Committee of the Ärztekammer Nordrhein, Düsseldorf, Germany. All subjects were moderately physically active, meaning they did not exercise more then three times a week on a 3 General Methods 33 regular basis. None of the subjects were involved in weight lifting or any other similar recreational sport. 3.4 Vibration Training Intervention 3.4.1 Vibration Training Devise During the VBR-Study, the Galileo 900 (Novotec Medical GmbH, Pfortzheim, Germany) was used as the training device (Figure 3.2). Figure 3.2: The ‘Galileo 900’ vibration platform The technical data of the platform are the following: Dimensions: Height 190 mm / Ø 700 mm Height with rail: ca. 1250 mm Weight: 50 kg Amplitude: 0 – 5.3 mm (peak – peak) Frequency range: 5 – 30 Hz The Galileo vibration platform produces a sinusoidal signal. Differently than all other plates on the market, the platform produces reciprocating vertical displacements of the left and right side of a fulcrum like a compensator (Figure 3.3). 3 General Methods 34 Figure 3.3: Mode of operation of the Galileo 900 Vibration platform. 3.4.2 Vibration Training Protocol The vibration training was applied twice daily in the bed rest period when subjects received the training intervention. Training sessions were scheduled at least 30 minutes after breakfast and lunch. Subjects walked a defined path to the training room. The distance was recorded with an accelerometer-based activity monitor (AMP331; Dynastream Innovations Inc., Cochrane, Canada). Each vibration training unit included 5 times of 60 seconds of isometric exercise units on the vibration platform in an upright standing position with a knee flexion angle of 30°. The vibration platform vibrated with a frequency of 20 Hz and with about 3 mm amplitude at the centre of the foot. Subjects carried an additional weight of 15 % of their bodyweight which was adjusted to a diving belt. Other studies like the ‘Berlin Bed Rest Study’ have used the so called ‘space galileo’ (Bleeker et al., 2005; Blottner et al., 2006; Mulder et al., 2007), which is designed for training application in the supine position. In our VBR-Study, the subjects trained in the upright position, although confined to bed rest which was done deliberately. From the researcher’s perspective we felt that the training intensity could be controlled more accurately in that position. With training in an upright position, subjects had to carry their body weight and the load could be increased with free weights. Also, by defining joint angles and the position of the body on the plate, the transmission of the vibration could be better controlled and reproduced which meant standardization of the training was easier to achieve and the scope for the individual subjects to perform the training differently was smaller. The joint angle was controlled at the beginning of each exercise with a metal angle. A goniometer was attached to the knee joint in order to have a visual control of the knee joint movement. Between exercise units subjects rested for 60 seconds while sitting on a chair. 3 General Methods 35 During the control intervention, everything, except for the vibration of the plate, was completely identical with the intervention phase (e.g. schedule, additional load, standing-sitting-rhythm). The control intervention was designed for the purpose of investigating the difference in the response between the bed rest with vibration training and the bed rest without vibration. Consequently, the treatments were identical except for the application of vibration. We were then able to interpret the real ‘vibration effect’. Figure 3.4: Position during the training intervention in the VBR-study. 3 General Methods 3.5 36 Diet 3.5.1 Meal Schedule Beginning with the adaptation period subjects received a controlled diet throughout the entire study phase. They ate 3 main meals per day and 3 snacks per day at predefined times (Table 3.2). Additionally the fluid supply was constant and controlled. Table 3.2: Meal schedule for the VBR-Study Time 08:00 10:30 13:00 16:00 19:00 21:30 22:30 Meal Breakfast Snack 1 Lunch Snack 2 Dinner Snack 3 Drink Subjects were asked to consume their meals completely at a specific time. If the meals could not be served at that time due to experiments, they ate them earlier or later, depending on the requirements of the experiments. Occasionally, snack, lunch or dinners were given at the same time. The food menu and the meal frequency were identical for each subject in both study phases to avoid any impact of nutrients other than the controlled foods. 3.6.1 Nutrient Intake The diet of the test subjects was individually tailored according to their body weight. Energy expenditure was calculated by summing up the resting metabolic rate (RMR) according to the WHO-equation (DGE et al., 2000), plus 10% of RMR for energy expenditure because of thermogenesis from food and beverages, plus 40% of RMR for the light physical activity during the adaptation phase (corresponds to a PAL (physical activity level)-value of 1.4) and the recovery phase or 10% of RMR during the 6°-HDT-phase. Dietary protein, fat and carbohydrate intakes were calculated according to dietary reference intake values (DRI, Ref) (protein: 1g / kg BW; fat: < 30% of total energy expenditure (TEE); carbohydrate: 55 – 60% TEE). The relation of vitamins and minerals also matched the DRI; the diet consisted of 200 mmol Sodium (Na+)/day and 1000-1150 mg Ca/day. Subject were given 50 ml water * kg BW -1 . All food items varying in sodium content, like bread, cakes or pastries were homemade. Predefinition of the daily menus for each subject was done using ‘PRODI’-software (PRODI Version 4.5 LE 2001, Nutri-Science GmbH, 3 General Methods 37 Karlsruhe). Subjects received the exact amount of the food that was predetermined and this was done by weighing the ingredients, the food items, and the beverages for each subject on a laboratory scale with a precision of 0.1 mg. 3.6 Environmental Conditions The clinical research center was completely air conditioned thus it was easy to control and standardize the environmental conditions independently from the time of the year when the study period was performed. The control of the environmental conditions was important in order to avoid sweating or freezing which may affect energy expenditure. Room temperature and humidity were recorded three times a day at 8:00 am 16:00 pm and 24:00 pm. The mean values were 23.0 ± 0.9 °C for temperature and 54.0 ± 5.7 % for humidity. 3.7 Physiotherapy Subjects received physiotherapy every second to third day during the bed rest period. Some subjects suffered back pain from lying in bed and a light massage minimized the pain and also to prevented it. All subjects were treated in the same way for both study phases and the treatment consisted mainly of a light massage. Consequently, we do not expect that this treatment affected our results. 3.8 General Statistics When measurements are taken and recorded, statistical analysis is needed in order to organize, present and treat the data so that interpretation may occur (Vincent, 2005). Statistical analysis can be distinguished between descriptive and inferential statistics. Descriptive statistics, which simply describe the conditions and results of measurements, will be used in this doctoral thesis to analyze the results of the measurements (e.g., by giving the means and standard deviations of the measurements and to describe the properties of the subjects, the environmental conditions, and other variables). The comparison among population means that are based on samples from the population will be done by using inferential statistics (Vincent, 2005). One assumption using inferential statistics is that the mean of a sample of a population gives an estimate of the mean of the whole population. A prerequisite for this assumption is that the sample has to be randomly selected. However, using inferential statistics, one can never be 100% sure about the correctness of the 3 General Methods 38 judgment or estimate one has made. It is always a statement made with a certain level of confidence. For example, if we claim that there is a difference between two population means with 90% or 95% confidence, the corresponding values of p would be 0.10 or 0.05 respectively. Another example is the estimate of a population mean based on a sample of the population. In this case, the standard deviation or standard error of a mean indicates the size of the error that may occur when using a sample mean. Sometimes, a 95% confidence range may be used. The accuracy of the estimate of the population mean based on a sample depends on the sample size and the precision of the experimental methods. With decreasing sample size the risks of a biased sample mean increases. When performing statistical analysis, there is always the risk of mistakenly rejecting or accepting the Null-Hypothesis, which is referred to as making type I and type II errors respectively. In order to create a balance between the risks of making type I and II errors, the p-value should be chosen carefully. Critical to the decision of the pvalue is the consequence of making each type of error. The decision should always protect against the most costly error (Vincent, 2005). The only way to reduce the risks of making the two types of errors simultaneously is to increase the sample size. The used cross-over-design used in this study has two advantages: (a) the same group of subjects participated in the measurements under different conditions. Thus, the differences in the results would be only caused by different experimental conditions rather than by different groups of subjects and (b) for the given limited number of subjects, this is a way to make the sample size not too small. Statistical analysis for all experiments in this doctoral thesis was performed using the software “Statistica 7.0” from Statsoft (Tulsa, USA). Depending on the type of measurements, either Student t-Tests or Analysis of Variance (ANOVA) has been used for statistical analysis. For more details on the specific statistics, see the method sections in the respective chapters (4 – 6). Dependent t-tests were used for the experiments where only pre- and post-bed rest measurements were performed (e.g. balance, cartilage thickness). With the Student’s t-test, it can be judged whether the means of two populations are different based on the means, standard deviations and the sizes of the samples from the populations. There were the following assumptions: o the population was normally distributed, o the samples were randomly selected from the population, o the data were parametric. 3 General Methods 39 For experiments with multiple measurements of the same group of subjects repeated measures ANOVA was used. One of the assumptions for repeated measures ANOVA is the homogeneity of variance and the homogeneity of covariance, collectively referred to as sphericity (Vincent, 2005). The probability of making a type I error increases when the assumption of sphericity is not met. Greenhouse Geiser and Huyah-Feldt adjustments were used in this thesis in order to correct for a violation of the assumption of sphericity. A Post Hoc test was performed by using the Tukey’s test. 4 Muscle Performance 4 4.1 40 Muscle Performance Specific Background The status of muscle mass as well as muscle performance of an individual depends on the individual activity level. It can only be maintained through usage. Disuse consequently leads to atrophic processes of muscle. Prolonged disuse of muscles can occur either due to bed rest after injury and illness or in situations of prolonged unloading as in space travel. Compared to gravity conditions, where we walk and move using our legs at least half of the day, in space, the leg muscles are used infrequently. In space flight, the possibility of long term missions (e.g., a space trip to Mars) and the lack of appropriate training methods accentuates the need to develop new training methods in order to prevent atrophy of skeletal muscle. The decreased muscle performance leads to health problems as soon as astronauts return to a gravity environment. Resulting training methods of space studies could also be applied to patients or elderly people with an inactive lifestyle. 4.1.1 Immobilization / Spaceflight The lack of gravity, compared to a gravity environment, during space travel leads to a mechanical unloading of the lower extremity. Several studies reported changes in muscle performance, muscle architecture and muscle biology due to space flight. Generally, long term exposure to microgravity (e.g., the Skylab missions), causes decreased muscle performance and muscle size (Thorton and Rummel, 1977). Most of all, anti-gravity muscles that are responsible for locomotion and postural control, are affected by microgravity (Aubert et al., 2005). For human skeletal muscle, data suggested that leg extensors atrophy faster than flexor muscles and showed also an earlier loss in peak force (Greenleaf et al., 1989). The same authors suggested, that the longer the missions are, the more similar are the responses of different muscle groups (Greenleaf et al., 1989). Other authors reported a decline of maximal voluntary contraction for the calf plantar flexors of up to 48% after a 6 month period on the space station MIR (Zange et al., 1997) and an average decline of 17% after 90 -180 days in microgravity (Lambertz et al., 2001). It has been suggested (Fitts et al., 2001), that the observed decreases in peak force may be due to muscle atrophy and the selective loss of muscle protein (Fitts et al., 2000; Fitts et al., 2001). Spaceflight also seems to have caused a greater atrophy in the soleus than in the gastrocnemius fibres (Fitts et al., 2001). Fitts et al. (Fitts et al., 2001) stated that this 4 Muscle Performance 41 may be caused by a shift in the neuronal recruitment, favouring the soleus over the gastrocnemius muscle within the calf. Another reason, that has been suggested is that muscle with larger fibre diameter during pre-flight showed greater atrophy than muscles with smaller fibre diameter (Edgerton et al., 1995; Fitts et al., 2001; Widrick et al., 1999). Although there are no space mission data on muscle protein content, Fitts et al. (Fitts et al., 2001) suggested the previously shown loss of force per crosssectional area in the slow type 1 fibres (Widrick et al., 1999) may indicate a selective loss of slow myosin in humans. In animals, it could be shown, that a 12.5-day space flight led to a significant decline in myofibril content of the slow-twitch vastus intermedius but not in the fast-twitch vastus lateralis fibres (Baldwin et al., 1990). Animal studies also showed that within 1 week of exposure to microgravity, muscle mass in rats decreased up to 37% (Fitts et al., 2000). Additionally, muscles with mainly slow-twitch fibres in rats atrophied more than fast muscles and the reduction in muscle mass was more pronounced in the leg extensors, than in the flexors (Jiang et al., 1992; Ohira et al., 1992; Tischler et al., 1993). However, data on humans showed a high variability of the observed changes between individual astronauts and to date, it is not known whether the high variability was caused by different in-flight countermeasure treatments or was a true difference in the sensibility of skeletal muscle to microgravity (Fitts et al., 2000; Fitts et al., 2001; Lambertz et al., 2001; Zange et al., 1997). It is acknowledged that data collected during space flight are rare and the level of control in terms of pre-flight training level, in-flight training intensity and nutrition are limited. Also, astronaut’s motivation to exercise during a mission as well as the opportunities for work out, vary between missions. To overcome these limitations of in-flight data, models have been developed that can simulate some of the effects of microgravity on the human body and also establish an environment that allows for more controlled conditions compared to space flight. Bed rest at 6°-head-down-tilt limits the weight bearing activity on all postural body structures and tissues (Adams et al., 2003) and leads to a fluid shift towards the upper body. Thus, this model can simulate the effects of microgravity on skeletal muscle structure and function (Kakurin et al., 1976) and data from a ground based model can be used to support findings that have been collected from in-flight data. Also, using the bed rest model, it is possible to transfer the results from such studies to other situation where disuse decreases muscle mass and muscle performance, such as aging or illness. Additionally, in bed rest studies, investigators are able to control nutrition and exercise during the study and 4 Muscle Performance 42 it is possible to measure a true control group. Adams et al. (Adams et al., 2003) compared muscle performance data from several different space flights and bed rest studies and found that generally, bed rest data and in-fight data over the same time frame show similar results in loss of muscle performance. However, it has to be taken into account that in-flight data usually represented the effect of microgravity plus a certain amount of training as a countermeasure whereas bed rest data included no countermeasure. Consequently, they concluded that the decreases would even be greater in space fight than in bed rest studies (Adams et al., 2003). Results from bed rest studies also suggested, that most of the muscle atrophy of the lower extremity muscles occurred in the first 2-3 weeks after unloading and it seemed that the rate of loss decreases (Adams et al., 2003) with increasing time in bed rest. 4.1.2 Countermeasures Several countermeasures have been developed since humans have travelled into space. To date, the suggested amount of training for astronauts is 2.5 hour / per day. The ISS is equipped with a treadmill, a cycle ergometer, electrostimulation devices and a strength training device. So far, the astronauts are not compelled to train and their training duration depends on the motivation and also the amount of free time they have, depending on their working schedule. Thus, training times vary a lot between astronauts and most of them perform less than 2 hours of training per day and sustain substantial losses in muscle mass. Although some astronauts voluntarily perform a high training volume, they still remain susceptible to the negative effects of spaceflight on the musculoskeletal system. 4.1.3 Vibration Training Attempting to increase the efficiency of strength training that may affect all tissues of the musculoskeletal system, in the past decade, vibration training became very popular as a complement to regular strength training (Jordan et al., 2005). An increasing number of studies have been published every year. The results have also been published in various reviews (Cardinale and Wakeling, 2005; Issurin, 2005; Jordan et al., 2005; Luo et al., 2005; Mester et al., 1999a; Mester et al., 2006; Nordlund and Thorstensson, 2006; Rehn et al., 2007). During whole body vibration training, the subject performs isometric or dynamic exercises on a vibrating platform. Currently, there are two major types of vibration 4 Muscle Performance 43 plates. One type of plates produces an oscillating sinusoidal signal where the whole plate moves uniformly up and down. The other model of vibration plates produces reciprocating vertical displacements of the left and right side, similar to a compensator. In addition to the regular parameters such as intensity, repetitions and amount of series of a specific exercise, training protocols for vibration training can be adjusted in frequency, amplitude and magnitude. For safety reasons, it has been suggested to exercise only on the vibration plate with flexed knees, as this position minimizes the transmission of vibrations to the head (Cardinale and Rittweger, 2006). Various vibration frequencies between 15 Hz and 90 Hz have been used to either achieve adaptations in skeletal muscle or bone (Issurin, 2005; Rubin et al., 2002a). The results of the studies investigating the acute effects of vibration training have been controversial thus far. Torvinen et al. showed increasing jump height and isometric knee force (Torvinen et al., 2002a) after 4 minutes of vibration training. Bosco et al. reported increasing serum levels of testosterone and human growth hormone after 10 sets of 60 seconds of whole body vibration (Bosco et al., 2000b) indicating the augmentation of anabolic processes. Other studies investigating the acute effects of vibration training found a decline in muscular performance (De Ruiter et al., 2003; Torvinen et al., 2002a). Studies on chronic effects of vibration training revealed that over a longer training cycle, vibration training could be beneficial for muscle performance. Several studies showed positive training effects on strength and power (Issurin et al., 1994; Issurin and Tenenbaum, 1999; Liebermann and Issurin, 1997; Mester et al., 1999a). For example, 21-days of training of a well trained alpine skier lead to a 43% increase in isometric muscle performance (Mester et al., 1999a). Increased performance could be the result of an improved synchronization of motor units and an improved co-contraction of the synergistic muscles (Jordan et al., 2005). Also, the ‘tonic vibration reflex’ (Hagbarth and Eklund, 1968) has been described as one of the underlying physiological processes which leads to a reflex induced muscle contraction that is mainly caused by the stimulation of the muscle spindles (Burke et al., 1976). On the other hand, vibration inhibits the stretch as well as the H-reflex (Desmedt and Godaux, 1978). Additionally, it can be assumed that vibration training also stimulates many other sensory structures in the effected tissues such as tendons, ligaments, cartilage and bone which consequently may lead to an adaptation of these structures to the vibration stimulus. Jordan et al. (Jordan et al., 2005) stated that the variability in outcomes of vibration studies could be a result of the differences in the training protocols. Most of the 4 Muscle Performance 44 protocols used so far, vary in vibration characteristics: position on the plate, performed exercise on the plate, additional load and others. It is very likely that each of these parameters affects the physiological response to the applied training. Therefore, there is a need for well controlled studies to explore the effects of vibration training. Vibration training would be applicable in space as it would still be possible to accelerate a certain mass, in this case a body, although it is weightless. To use vibration training, it would be necessary to secure the astronaut to the plate with a belt system, which also is used for in-flight training on the treadmill or the cycle ergometer. 4.1.4 Purpose of the Study and Hypotheses As previously discussed, disuse as in bed rest during illness, sedentary lifestyle or space travel induces a reduction in muscular performance. To date, time efficient countermeasure programs are still lacking. Several different studies so far investigated the effects of vibration training on muscle performance; however, there is a lack of controlled studies. Additionally, the results of vibration training are controversial. Therefore, the purpose of this study was to investigate the combined effect of unloading during 14-days of 6°-HDT bed rest and daily vibration training on maximal voluntary contraction (MVC) and maximal power of the knee flexors and knee extensors. It was hypothesized, that (a) 14-days of 6°-HDT bed rest without training would lead to a reduction in MVC and maximal power for the knee flexor and extensor muscles and that (b) bed rest with vibration training would lead to a smaller reduction in these parameters or even avoid any losses in muscle performance. 4 Muscle Performance 4.2 45 Specific Methods 4.2.1 Muscle Performance Testing Strength performance testing was conducted three times throughout each study phase (Table 4.1) (see also (Schmidt, 2006). The series of measurements started with a baseline measure at day -1 of the adaptation phase, which was the day directly prior to bed rest, followed by a re-test at day R1 of the recovery phase after the subject got up from the bed rest and finished with a last measure at the R5 of the recovery period. Measurements were performed in the laboratory of the Institute of Training Science and Sport Informatics at the German Sport University in Cologne, Germany. All measures of muscle performance were carried out at the same time of day in the afternoon. At day R1 the measurement was performed approximately 24h after the last vibration training session and approximately 8h after subjects left the 6°-HDT position. Muscle Performance Vibration Training Table 4.1: Study design of the VBR-Study. Muscle Performance was measured during the Adaptation and the Recovery period. In the intervention phase subject were immobilized at 5°-HDT-bed rest. During that time period, subjects either engaged in vibration training or the control intervention. Regular strength training devices (Gym 80, Gelsenkirchen, Germany) equipped with a force transducer and a displacement transducer (mechaTronic GmbH, Hamm, Germany) allowed us to measure isometric and dynamic forces for the knee extensor and knee flexor muscle groups. Data recording and data analysis was performed with the commercial software (windigi, DigiMax, mechaTronic GmbH, Germany, Version 8.1). The two parameters measured were maximal voluntary contraction and power for the knee flexor and knee extensor muscles. Prior to the strength test, subjects performed a 5 minute warm up on a treadmill at 2.5 m / s walking speed. Also all subjects had to perform a specific warm up at each R5 R4 R3 R2 R1 14 13 12 11 Recovery 10 9 8 7 6 5 4 3 2 Intervention 1 -1 -2 -3 Experiment Day -4 Adaptation 4 Muscle Performance 46 of the training devices consisting of 1 set of 8 repetitions with a load of 5 kg. This specific warm up was supposed to give the subject the chance to get used to the device as well as to the movement they were asked to do. All training devices were adjusted to the individual anthropometric values, meaning that for the dynamic as well as the isometric measures, joint angles were used to reflect the optimal joint position for the specific movements (Baratta et al., 1988; Herzog et al., 1991; Savelberg and Meijer, 2003; Solomonow et al., 1987; Ullrich and Brueggemann, 2007). The goal of controlling the joint angles for each subject individually was to get as close as possible with the used methods to an optimal muscle length for the required movement. Settings of the training devices were identical for all repeated measurements. 4.2.1.1 Isometric Measurements For isometric maximal voluntary contraction (MVC) measurement the lever arms of the training devices were adjusted, to reduce, as much as possible, any additional movement. Joint positions were set at 60° knee flexion and 90° hip flexion for the knee extensor measurements and 20° knee flexion for the knee flexor measurements. After the specific warm up, the lever arm was adjusted and the subjects were asked to perform one test trial followed by three real MVC measurement. After receiving a previously learned command, they pressed, to the maximum, against the resistance with both legs at once. Between repetitions, subjects had a 120 seconds break. No verbal motivation was used throughout the study to ensure consistent conditions for all six measures of muscle performance. The highest force out of the three recorded values was included as MVC into the statistical analysis. Subjects were deprived of their reached maximal strength values in order to minimize a personal bias. 4.2.1.2 Dynamic Measurements For the dynamic measurements, the mass that had to be accelerated was adjusted to the individually determined 50% MVC. Thus, the mass was recalculated for each of the strength testing sessions throughout the study. When the MVC decreased, consequently the mass subjects had to accelerate decreased as well. The maximal power achieved in this measure was included into the statistical analyses. 4 Muscle Performance 47 4.2.2 Statistical analyses Statistical analyses were performed using STATISTICA software (Version 7.0, StatSoft, Inc., Tulsa, USA). Randomization of subjects was tested using factorial analyses of variance (ANOVA) prior to all other statistical tests. The time effects of bed rest and vibration training on MVC and maximal power values were tested using repeated measures ANOVA. Data for the control intervention and the vibration training intervention were compared using ANOVA within-within. Significant differences were adjusted using Greenhouse Geiser correction and Huynh-Feldt (HF) adjustments. Post hoc tests were performed in order to further analyze time effects for the different days. Differences were regarded to be statistically significant at P < 0.05. All results are shown as means ± SD. 4 Muscle Performance 4.3 48 Results Factorial ANOVA revealed no effect of the randomization of subjects to the order of the treatment. There was no difference in baseline performance levels between the two groups. Also, it did not affect the results whether subject started with the control or with the vibration training intervention; hence, there was no learning effect between the two different study phases. Thus, the subsequent statistical analyses of the data were divided only into the two intervention groups. Maximum voluntary contraction (MVC) did not decrease significantly for the knee flexor and knee extensor muscles when subjects receive bed rest only (Table 4.2 and 4.3). When subjects received vibration training, there was a significant decrease in MVC for the knee flexor muscles (p=0.003) but not for the knee extensor muscles. Maximal power at 50% of the MCV values did not change significantly throughout the time course of measures for the knee flexor muscles. However, there was a significant decrease in maximal power of the knee flexors when subjects received vibration training (p=0.047). Table 4.2: Effects of HDT bed rest on muscle performance for knee extensors and flexor muscles. Vibration training could prevent a decrease of maximal power in the knee extensor muscles. When subjects received the control intervention, maximal power decreased significantly (p=0.007), whereas there was no statistical significance in maximal power when subjects received vibration training. These results were 4 Muscle Performance 49 confirmed by an ANOVA within-within, where a significant difference in the effect of the two treatments was found (p=0.001). When MVC or maximal power showed a significant reduction in the achieved values, subjects did not recover to baseline levels after the five day recovery period. In contrast, the maximal power and MVC of the knee flexors values further decreased, although subjects were mobile in the laboratory again (see Table 4.3). Table 4.3: Muscle performance for the knee extensor and knee flexor muscles before and after HDT bed rest. Following are the results for the control and the vibration intervention. Asterisks indicate a significant difference (p < 0.05) between baseline and the respective value. Intervention pre-HDT post-HDT post-HDT (day -1) (day R1) (day R5) 1287 ± 314 1190 ± 209 1168 ± 219 -5 % -6 % 1240 ± 213 1188 ± 200* -4 % -7 %* 614 ± 134 617 ± 122 -2 % 3% 676 ± 157 608 ± 167* -7 % -10 %* 2196 ±445 2131 ± 440 -2 % -6 % 2076 ± 460 2253 ± 642 -9 % -2 % 811 ± 237* 871 ± 253 -12 %* -5 % 825 ± 201 801 ± 250 -12 % -7 % Knee flexors MVC [Newton] control % change vibration 1284 ± 206 % change Power [Watt] control 645 ± 196 % change vibration 699 ± 179 % change Knee extensors MVC [Newton] control 2250 ± 439 % change vibration 2305 ± 519 % change Power [Watt] control 915 ±211 % change vibration % change 927 ± 263 4 Muscle Performance 4.4 50 Discussion The purpose of this study was to investigate the combined effect of unloading during 14-days of 6°-HDT bed rest and daily vibration training on MVC and maximal power of the knee flexors and knee extensors. The first hypothesis, that 14 days of 6°-HDT bed rest without training would lead to a reduction in MVC and maximal power for the knee flexor and extensor muscles could not, in general, be confirmed. MVC did not decrease significantly for leg extensor and leg flexor muscles after 14 days of strict bed rest. This is surprising as 14 days of bed rest due to illness or 14 days of casting of a joint may have major effects on muscle performance. Deconditioning, due to injury or illness is often caused by total joint immobilization, for example, with a cast or caused by neural inhibition due to pain. Thus, the above conditions of immobilization are not comparable with the conditions to which our subjects were exposed to as they were allowed to move their joints as long as they did not leave the 6°-HDT-position. Additionally, they walked a defined path to the training room twice every day which did not affect the known effects of bed rest on the cardio-vascular system (unpublished data); however, it may have affected the impact of 14 days of bed rest on muscular performance. Pre-bed rest muscle and training status seem also to have a major impact on the deconditioning of muscle during bed rest. The subjects in our study were untrained. Thus, the activity level during bed rest plus walking some meters every day may not have been much different from their daily activity outside the lab. If this was the case, for our subjects bed rest, as the initial stimulus for detraining, may not have been effective. Wackerhage et al. (2006) (Wackerhage H. and Atherton P., 2006) hypothesized that there is a ‘moving threshold’ for the intensity that is necessary to initiate muscle growth. This would mean that an atrophied muscle needs less stimulation to start anabolic processes than a hypertrophied muscle. Other authors (Phillips et al., 1999) showed that in untrained subjects lower levels of resistance training lead to muscle protein synthesis than in resistance trained athletes. Possibly, the opposite mechanism holds true for detraining processes. For untrained subjects, lower levels of activity and longer periods of de-activation may be needed to initiate catabolic processes in skeletal muscle than in resistance-trained subjects. It also has to be considered that the energy intake of our subjects was controlled. This means that they consumed the amount of food required to be in a balanced 4 Muscle Performance 51 energy status (DGE et al., 2000). The massive decrease of muscle performance during space flight and in illness or injury induced bed rest is partly due to hypocaloric food intake (Biolo et al., 2007). Our results show that if subjects receive a diet tailored to their energy requirements, they do not necessarily show a decreased muscle performance. The chosen PAL-value in our study was at a level for primarily sitting daily activity. The finding that the subjects were in a balanced energy state with that chosen PAL-value also supports the statement that the activity level during the study may not have been much different to their daily activities for some of the them. Our data show that there is no general response of the lower extremity muscles to bed rest. The response of skeletal muscle to 14 days of bed rest is muscle specific. The maximal power decreases earlier and is more pronounced in knee extensor than in knee flexor muscles. This finding supports the results of previous studies, which reported earlier and greater losses in extensor muscles (Greenleaf et al., 1989). They suggested that the longer a space mission lasted, the more similar were the losses in muscle performance between different muscle groups. Atrophy may occur earlier and is more pronounced in muscles, for example, anti –gravity muscles, that are used extensively under gravity conditions (Aubert et al., 2005) as well as in muscles with larger diameter (Edgerton et al., 1995; Fitts et al., 2001; Widrick et al., 1999). The knee extensor muscle has one of the largest girths in most of the people and even in untrained individuals, it is one of the most frequently used muscles since it maintains the body in an upright position or lifts it against gravity. There is often a neuromuscular disbalance between the knee extensor and flexor muscles. Thus the knee flexor muscle may not recognize a 14-day bed rest period as a major change in the normal pattern of usage and therefore show a latent response. Additionally, the length of a muscle in immobilization is critical for the occurring effects. Although our subjects were not “fixed” in a certain position, they spent their days lying in bed with their knee joint extended most of the time. This meant a short muscle length for the knee extensors that would encourage the loss of sarcomeres from the ends of the fascicles. For the knee flexors, on the other hand, an extended knee position means that they are at their maximal length. Since the sarcomeres in series are one important factor for the maximal power of a muscle, the above mentioned “length theory” may explain the different responses of the two muscle groups. 4 Muscle Performance 52 In summary, the changes in MVC and Power after 14-days of immobilization of healthy subjects with controlled diet are muscle specific and may depend on the physical status pre-bed rest. The second hypothesis was that vibration training will lead to a smaller reduction or avoids losses in MVC and Power in knee flexor and extensor muscles. Vibration training lead to less decrease in power for the knee extensors meaning the rate of change in muscle performance due to bed rest could be decreased with the applied training protocol. A static squat position at a knee flexion angle of 30° activates the knee extensors as agonists more than the knee flexors. The superimposed vibration in this position may induce an eccentric load at the level of muscle fibres that is more effective for the knee extensors than for the knee flexors. More specific exercises on the vibration plate may also lead to less decrease in the knee flexor muscles. The bed rest intervention did not result in a significant decrease in the MVC values of our subjects. Thus, the expected decrease in muscle performance that we hoped to avoid with our training intervention could not be observed. This finding makes it more difficult to show positive effects of vibration training. With the volume and intensity of our training program, we did not intend to increase muscle performance. Taking this into account, it is not surprising that vibration training during bed rest did not lead to a much different response in MVC values than bed rest alone. If muscle performance decreased due to bed rest, as the power data for the knee extensors showed, vibration training could counteract this effect. The power data also show that although the MVC was the same before and after bed rest, the ability of the subjects to maximally accelerate a given mass, decreased. The decreased power could, for example, be caused by a lower intramuscular coordination or a change in the quality of muscle. Maximal power also depends on the length of the muscle, hence, the sarcomeres in series. Riley et al. (Riley et al., 2000) reported a decreased length in some fibres after short periods in space. That this holds true for the knee extensor again supports the finding that the knee extensors adapt earlier than the knee flexors. Only one comparable study has been conducted in recent years. In the ‘Berlin Bed Rest Study’, 20 male volunteer were immobilized for 56 days in head down tilt bed rest (Blottner et al., 2006). They received a combination of whole body vibration and resistance training twice daily for 6 minutes on the ‘Galileo Space’ device at frequencies between 19 and 25 Hz. The group found that the vibration training group showed less reduction in maximal voluntary contraction of the plantar flexors. 4 Muscle Performance 53 Additionally, they showed an increase in soleus myofibres type I and type II in the vibration training group and suggested this could be due to hypertrophy. Unfortunately, a control intervention with “vibration-only” or with “resistive exercise only” was missing in this study. Consequently, it was not possible to distinguish between vibration and resistance training effects. The findings of the ‘Berlin Bed Rest Study’ are not in conflict with the results of this study as the length of immobilization is much different. It may be that atrophic processes start later than after 14 days off bed rest if nutrition is controlled and subjects are not in a cast. However, our results would support the hypothesis that vibration training may act as a potential countermeasure for bed rest induced muscle atrophy. Maximal velocity and power give a different insight into muscle function and possible adaptations of space flight. Whereas the maximal voluntary contraction (MVC) only reflects the alterations in strength at one given joint angle, the force-velocity relationship describes the amount of force that can be produced at any given shortening velocity. The product of force and velocity is mechanical power, which is an important functional measure. Maximal force is mostly dependent on the number of sarcomeres in parallel, whereas Vmax is highly dependent of the sarcomeres in series. Due to technical limitations, the effect of microgravity on the force- and power-velocity relationship is inadequately studied (Adams et al., 2003) so far. The force-velocity relationship of ankle plantar flexor and extensor muscle showed a reduction after long (110-237 days) as well as short (7 days) term missions (Grigoriev et al., 1991; Kozlovskaya et al., 1981). More specifically, the decreased strength in the ankle plantar flexor was greatest at high angular velocities. On the other hand, Trappe et al. (2001) found no effects of 17-days of space flight in the torque velocity relationship for the ankle plantar flexors (Trappe et al., 2001). 4.4.1 Limitations of the Design The vibration bed rest study was designed as a cross over study in order to account for the small number of subjects. Thus, it was possible to compare the effects for each subject individually as each of them conducted two interventions, the control and the training intervention. The training load was tailored to body weight. It may have been optimal to tailor the training intensity to each subject’s pre-bed rest training level. However, our subjects were not athletes, meaning they were not trained. We assumed, therefore, that their muscles’ work load was mainly carrying 4 Muscle Performance 54 their body weight. Therefore, normalizing the training load to body weight seems appropriate. Also, we did not increase the training load progressively, but it was consistent over the whole 14 days of bed rest. A progressive increasing training load may have led to more distinct differences between the training and the control group. Generally, we chose a relatively low training load. However, as this was the first study to implement isolated vibration training in a bed rest study and vibration training is recognized as a very intense training method, the main goal, besides, of course to prevent deconditioning, was to prevent injury to our subjects. It is recommended that future studies incorporate a higher training intensity and a progression of the training load to increase anabolic effects of vibration training. The upright training position has been chosen consciously. Compared to a lying position, we felt that training upright would provide more control of what the subjects actually did during their training. Also, the transmission of the vibration through the body is identical with the training situation in space and therefore seems more appropriate. In summary, during the vibration bed rest study, vibration training during 14-days of 6°-HDT bed rest led to less decrease of power in the knee extensors. Thus, the used training protocol was sufficient to minimize the decrease for power of the knee extensors. Surprisingly, bed rest did not lead to a decrease in MVC of knee flexors and extensors in our subjects. In conclusion changes in MVC and power after 14days of immobilization of healthy subjects with controlled diet are muscle specific and may depend on the physical status prior to bed rest. 5 Balance 55 5 Balance 5.1 Specific Background The ability to stabilize body position is mandatory for the performance of movement (Wilke, 2000) and is highly dependent upon the grade of experience. For example, gymnasts who exercise on the high beam, skateboarders and other individuals who are regularly exposed to an ‘unstable’ ground, perform much better in balance than others who do not force the ‘balance system’ as much. During spaceflight, the demands on the lower extremity muscles are reduced to a minimum which not only leads to changes in muscle performance but also affects the ability to stabilize body position. These changes in body control are not of much importance as long as the astronauts stay in a microgravity environment. However, as soon as they return to a gravity environment, for instance, to Earth, Moon or Mars, the degenerative effects can lead to major safety and injury risks (Hrysomallis, 2007). This is important to be aware of, especially when astronauts in the near future are on interplanetary missions, where they don’t have the physical support from team members on earth. As with most of the data obtained in space flight, the sample size is very small and it is difficult to generalize the results gained during spaceflight and draw conclusions for a normal population. However, knowledge obtained from spaceflight in that field is very important as it mimics the absence of load and gravitation on the human body perfectly. The rare occasion of having an astronaut as a subject led to the development of models that can simulate the effects of microgravity on the human body. Immobilization in 6°-head down tilt bed rest (HDT-bed rest) can simulate some of the effects space flight has on the musculoskeletal system. Recorded results from spaceflight or immobilization studies may help to better understand the processes involved in the ability to stabilize body position and even more importantly, to develop adequate countermeasures. 5.1.1 General Physiology The ability to “keep balance” is the result of the interaction of many different organic and reflex systems of the human body. To be able to coordinate movement and body position, the brain needs useful information about the position of the body in space. Proprioception is the sense of the position in space, where the sensory input is collected through sensors entitled mechano-receptors or proprioceptors. The different receptors can be classified by 5 Balance 56 the organs or tissues which they are located in, (e.g., joints, muscles, tendons, ligaments, the skin and the vestibular organs) and through their function (Table 5.1). The collected sensory information is then transmitted to the central nervous system (Shaffer and Harrison, 2007). Table 5.1: Mechano-receptors in humans Receptor Muscle Spindles Location skeletal muscle Function - sense muscle stretch - causes agonist contraction and antagonist relaxation Pacinian near joints in the deep Corpuscle subcutaneous tissue Golgi-Receptors tendons and ligaments - sense rapid changes in pressure and vibrations - low excitation level - measure tension - can enhance or inhibit muscle activity of the whole extremity - measure skin stretch Ruffini Endings joint capsule Free Nerve all tissues except cartilage - detect changes in pressure, Endings temperature, pain and stretch The vestibular organ is located in the inner ear and it represents a mechano-sensory organ. Its role is to stabilize the field of vision and to control the upright body position (Clarke and Scherer, 2001). There is a strong connection between the vestibular system and motor activity since the afferent information from the vestibular system is being used to stabilize eye movement and body position. Ocular counter rolling represents one example for an otolith-ocular reflex which occurs in response to the activation of the otholiths which are located in the inner ear (Moore et al., 2001). Receptors play a major role in reflex-loops as they deliver the afferent input signals. In postural control, the two important reflex loops are the vestibulo-ocular reflex and the vestibulo-spinal-reflex. The first enables the body to stabilize the field of vision as the head moves. Although this reflex loop is affected by a microgravity 5 Balance 57 environment, we will not include it here as we will not be able to measure the impact of bed rest on this system in the experiments performed in this study. The vestibulo-spinal-reflex is responsible for the regulation of the muscle tone that is necessary to keep the body in an upright position. To accomplish this, the vestibular system is connected with the “anti-gravity-neurons” that trigger the muscle spindle reflexes (Clarke and Scherer, 2001; Scherer, 1997). 5.1.2 Adaptation during Spaceflight and Immobilization 5.1.2.1 Spaceflight The absence of normal gravitational loading or immobilization as in injury, aging or disability, leads to changes in the sensibility of the receptors. This can result in the inability to estimate the position of the body in space correctly (Olivier and Fakler, 2005). In the long term, a complete “set” of input signals is necessary to be able to control the body’s equilibrium (Dietz and Duysens, 2000). The special conditions in space are characterized by a relatively low muscle activity that is necessary to keep the body in a balanced position (Edgerton et al., 2001; Lestienne and Gurfinkel, 1988). Since the sensory input for the lower extremity muscles is missing in microgravity, it has been shown that peripheral and central neural processes are physiologically and functionally altered when astronauts return from a stay in microgravity (Clement et al., 2005). Also, massive irritation of the control of body position and movement after a stay in microgravity have been investigated by different authors (Graybiel, 1980; Grigoriev et al., 1991; Homick and Reschke, 1977; Paloski et al., 1992b; Paloski et al., 1992a). The explanation seems obvious in that the anti-gravitational muscles showed the most severe atrophy of all skeletal muscle (e.g. (Edgerton et al., 2001) and they are the major muscle groups responsible for keeping the body in an upright position under gravitational conditions (Baroni et al., 2001a). Additionally, the function of receptors generally changes in a microgravity environment. Due to the microgravitational environment, all gravitationally dependent functions of the vestibular system are irritated which leads to “illusory motions” (Reschke et al., 1994; Reschke et al., 1998) and motion sickness with symptoms like dizziness and malaise (Mittelstaedt, 1999). The reason for motion sickness is mainly due to the inability of the otholiths to sense accelerations as their physiological functionality depends on the presence of gravity (Lackner and Dizio, 2000; Mittelstaedt and Glasauer, 1993). On the other hand, Ross et al. (1993) could 5 Balance 58 show in a rat experiment that the morphology of the vestibular organs, such as the otholiths, did not seem to be affected by microgravity. After 10 – 14 days of spaceflight, no changes in their morphological development could be determined. However, neuronal connections between the single sensory cells increased 12-fold (Ross, 1993) which indicated a high plasticity of the vestibular organs in response to changes of the environment (Clarke and Scherer, 2001). Beside motion sickness at the beginning of a flight, the main health issues associated with the effects of microgravity on balance occur after the return to a gravitational environment (e.g., earth). The re-adaptation to gravity also causes dizziness as in “motion sickness” (Clement et al., 2005), which is comparable to the swinging movement that people experience when they leave a boat after a longer trip and step on rigid ground again. Also, the response patterns of the muscle spindles change, as they sense a different length of the muscle due to the lack of gravity (Baroni et al., 2001b; Dietz et al., 1989; Matthews, 1981; Matthews, 1988). This results, for example, in the inability to reproduce a joint angle without visual control (Clement et al., 1984) after a stay in microgravity. Due to the negative adaptations of skeletal muscle to microgravity the vestibulospinal-reflexes also decrease which leads to difficulties in controlling an upright body position as well as the coordination of a uniform gait when astronauts return to earth (Clarke and Scherer, 2001; Clement and Reschke, 1996). As a result of that, the decrease of the vestibulo-spinal reflex leads to irritation of the muscle spindles (Reschke et al., 1984; Watt et al., 1986). In this context Roll et al. (Roll et al., 1993) stated that the weakening of the vestibulo-spinal reflexes could lead to lower excitation of the anti-gravity muscles which would explain the reduced ability to control movement and position during space flight. Roll et al. confirmed their results with experiments that could show only a limited ability to elicit the H-reflex in response to the application of vibrations on a tendon after 21 days in microgravity (Roll et al., 1993). The same experiment led to the conclusion that biomechanical properties of certain receptors also changed since they showed lower activateability of the proprioceptors. Cherepakhin et al. (Cherepakhin et al., 1973) studied the human sensorimotor coordination after 18 days of spaceflight. The ability to maintain the vertical posture decreased and it took 10 days after their return from microgravity until values were at baseline levels again. 5 Balance 5.1.2.2 59 Immobilization Decreased mobility usually causes decreased skeletal muscle performance which plays a major role in the ability to keep balance. For example, the strong synergy between agonistic and antagonistic muscles is very important for the intra- and intermuscular coordination and one should expect postural control to worsen with decreasing muscle performance. Immobilization always reflects a decrease in dynamic input signals. It is expected that with immobilization due to injury or trauma an “atrophy in dynamic receptors” can occur (Froböse et al., 2003). Muscle tonus is a result of the body’s challenge to keep an upright position against the force of gravity and it will be reduced after prolonged immobilization (Wiesendanger, 1997). During immobilization, the mechanisms that regulate the muscle tone receive smaller input signals from receptors, the vestibular system and the visual system which leads to an adaptation of skeletal muscle to the current conditions. All these mechanisms would also add to a decrease in coordination. Changes in the body’s ability to maintain equilibrium may also be caused by muscle atrophy. If, after atrophic processes, the body is challenged with stability exercises, the requirements for the muscle increase with the increasing difficulty of the exercise (Wilke et al., 2003). Thus, a decrease in skeletal muscle performance, due to injury or immobilization leads to the decreased ability of muscle to support the body in ‘keeping balance’. Davis et al. (Davis et al., 1997) investigated the effects of head down tilt bed rest on postural control. EMG measurement before and after 5 days of bed rest showed that immobilization increases muscle activity of the lower extremity during walking which corresponds to a decreased ability of postural control. Exercise interventions during the bed rest intervention could not counteract this effect. The group limits their results to the finding that the used protocol may not have been sufficient to counteract the bed rest effect. It is also noted that longitudinal electromyographic studies face specific problems in the standardization and calibration of the signals. Different studies showed a reduction of electromyographic activity during immobilization (Alkner and Tesch, 2004) as well as a change in conduction velocity (Rüegg et al., 1998). The conduction velocity decreased due to a smaller muscle cross sectional area and a recovery to normal values needed approximately 14 days of normal mobilization. 5 Balance 60 5.1.3 Vibration Training The application of vibrations to the human body activates the neuro-muscular system (Haas et al., 2004) and consequently, should also effect the coordination of movement. As previously described, many studies investigated the effect of vibration training on performance parameters as maximal force or power (see chapter 2.3.4.2) and although the results are controversial it seems more likely that vibration training does have the potential to elicit anabolic processes. If this method is able to enhance muscle performance, there should also be an effect on the coordinative portion of movement. Also, if one studies the properties of mechanical receptors, it becomes clear that they are sensitive for the properties of a vibratory input signal, especially the Pacinian corpuscle. Studies on the effects of vibration training or vibration stimuli on balance and coordinative processes have mostly been performed in medical environments, for example in the context of rehabilitation of orthopedic injuries or in the prevention of risks in falling for elderly people (Ahlborg et al., 2006; Bautmans et al., 2005; Bogaerts et al., 2006; Brunetti et al., 2006; Bruyere et al., 2005; Gusi et al., 2006; Kawanabe et al., 2007; Torvinen et al., 2002a; Torvinen et al., 2002b; Torvinen et al., 2003). Berschin et al. (Berschin and Sommer, 2004) observed an increased co-activation of synergistic muscle groups in response to vibration training which is necessary for joint stability. Therefore, they suggested to using this training method as a tool in the rehabilitation of anterior cruciate ligament (ACL) deficient patients as well as for the prevention of injuries in people with predisposed joint instability. Also, they stated that vibration training may stimulate receptors that have been affected through the injury as well. Vibration training can influence movement control in terms of an incorrect estimation of joint angles (Cordo et al., 1995). The irritation of the proprioception is thereby dependent on the vibration frequency (Kasai et al., 1992), the velocity of movement (Steyvers et al., 2001) and the activation level of the muscle (Haas et al., 2004). Furthermore, vibration can lead to body tilting if calf muscles are stimulated during quiet standing (Eklund, 1972) or to movement illusions if the trunk is fixed and thus unable to move (Lackner and Levine, 1979). These effects are dependent upon the stability of the supporting surface upon which the subjects stand. They are attenuated if the subjects stand on an unstable surface (Ivanenko et al., 1999). Experiments during walking showed that vibration of the thigh muscles altered the 5 Balance 61 walking speed depending on the direction of the progression (Ivanenko et al., 2000). Ivanenko at el. (2000) concluded that the proprioceptive input from the muscle spindles is important for the maintenance of a steady state during human locomotion. The proprioceptive influence of the muscle spindles is task specific and it seems that the information about the movement of the foot relative to the trunk is important for the control of the walking speed. Vibration training is being successfully applied for the prevention of risks in falling among elderly people. Bruyere et al. (2005) reported an improvement of health related quality of life in nursing home residents. They improved their walking ability and minimized the risk of falling after 6 weeks of whole body vibration compared to the control group (Bruyere et al., 2005). A different group confirmed these findings with improved performance of timed up-and go and the Tinetti-test after 6 weeks of vibration training with nursing home residents (Bautmans et al., 2005). Kawanabe et al. (2007) only recently investigated the effect of a 2 month vibration training program added to an exercise routine compared to the exercise routine only for elderly people. Although subjects trained only once a week, they improved walking speed, stride length and standing time on one leg compared to the control group (Kawanabe et al., 2007). Vibration training becomes also popular as a training method in the treatment of neurological diseases and injuries such as Parkinson Disease (Novak and Novak, 2006; Turbanski et al., 2005), Multiple Sclerosis (Schuhfried et al., 2005) and paraplegic patients (Melchiorri et al., 2007). Postural control of patients with Parkinson Disease, for instance, could be enhanced spontaneously with a treatment of 5 x 60sec of vibration at 6Hz (Turbanski et al., 2005). Postural stability was enhanced after the training and Turbanski et al. (2005) stated that it may serve as an alternate treatment method that could potentially enable the patients with Parkinson Disease to adopt a more active way of life. 5.1.4 Purpose of the Study and Hypotheses In summary, the observations of the effects of spaceflight on balance previously described, show, that a decrease in balance ability can become a major health risk in space flight since it can lead to injuries. The development of good training programs that avoid these effects is very important and can also have an impact on the design of rehabilitation or prevention programs for elderly people who also show an increase in risks of falling and consequently are at higher risk for bone injuries. 5 Balance 62 The effects of head down tilt bed rest on balance performance under controlled conditions remain unknown. Vibration training seems to be a promising complement to regular strength training and additionally may have an impact on balance performance, as previously described. Therefore, the purpose of our study was to investigate the effects of 14-days headdown-tilt bed rest on balance performance as measured with the Posturomed® device and to test the impact of a vibration training protocol on the effects of bed rest. The hypotheses were the following: a) 14-days of head down tilt bed rest negatively affects the ability to stabilize body position as measured with the Posturomed® device; and b) Vibration training during 14-days of head down tilt bed rest can minimize the negative effects of immobilization on balance performance. 5 Balance 5.2 63 Methods 5.2.1 Posturomed® Device In this study, ‘balance’ is defined as the ability to stabilize body position. Following, both of the terms ‘balance performance’ and ‘balance ability’ will be used in reference to the ability to stabilize body position. For the balance experiment, the Posturomed® device (Haider Bioswing, Euskirchen) was used (Figure 5.1). The device is built out of three main elements that are mounted on top of each other: a platform, an intermediate plate and a ground plate. The platform is the top layer and is coated with a plastic material to avoid slipping. It is 60 cm X 60 cm and can swing in two directions, anterior-posterior and mediallateral. For safety reasons, the platform is surrounded by a handrail on three sides which gives the subjects or patients something to hold on to. Figure 5.1: The Posturomed® device used in the study The platform is attached to 4 special ‘Bioswing’-swing devices that allow for movement in two independent swing circles. The amplitude of the platform can be adjusted with the help of two brakes that are attached to the side of the Posturomed®. This results in three levels of difficulty: free swing in two directions, free swing in one direction and constricted swinging in both directions (Rasev and Haider, 1995). 5 Balance 64 The Posturomed® used in the study was equipped with an accelerometer at one side of the platform that could sense accelerations of the plate in the horizontal plane in the two described directions (see Figure 5.2). Additionally, sensors were attached to the platform that recorded changes in the path-time course of the plate. The data were recorded at 500 Hz sampling frequency, then transferred through an amplifier to an analogue / digital transducer and finally processed with special software in the associated computer. Afterwards, a mechaTronic software enables the user to display the movement of the platform on the screen. All technical data and technical details are also described by Rasev and Haider (1995). Figure 5.2: Position-time diagram of the Posturomed®. Using the Posturomed® device, ‘balance’ is described in the displacement of the platform in mm in the two different directions. A good ability to balance the body is defined through a small displacement of the platform in either direction, whereas big displacements are considered to reflect a bad ability to stabilize the body position (Schlumberger and Schmidtbleicher, 1998). An additional feature to measure balance ability is a displacement mechanism (Müller et al., 2004). It enables the researcher to assess the reactive ability to stabilize the body. Subsequently, this test will be named ‘provocation’. The platform 5 Balance 65 is dislocated and adjusted in the medial-lateral direction by 20 mm. When eliciting the fixation, the platform follows gravity and swings sideways. The subject is asked to re-stabilize as fast as possible again. The Posturomed® device has been used in the diagnosis of balance and also in the training of sensori-mortor and neuro-muscular abilities (Wilke et al., 2003). 5.2.2 Test Protocol The balance test was performed on study-days -4 and R1. In the morning of day -4 an extra session was performed in order to familiarize with the experiment. The goal was to minimize the learning effects as much as possible in order to prevent the results from being biased by such an effect. Therefore, the subjects were introduced to the Posturomed® device and the different tasks they had to perform. This is very important, especially for the subjects with lower balance ability. These trials were also recorded in order to compare, if necessary, the values with the second pre-bed rest session. The actual data collection was done in the afternoon of day -4. The results of the pre-bed rest measure were considered the ‘normal’ values and postbed rest values were related to these values. The post-bed rest measurement was conducted on day R1, immediately after subjects finalized the immobilization period with the tilt-table-experiment. All subjects walked a distance of about 15m from the tilt table experiment to the testing room for the balance experiment. Procedures were identical for the control and the vibration condition. The whole balance experiment consisted of 6 different tasks that increased in their degree of difficulty (Jansen, 2006). Task 1: two legged – open eyes Task 2: two legged – closed eyes Task 3: one legged – open eyes (left and right leg alternately) Task 4: one legged – closed eyes (left and right leg alternately) – free leg at the height of the ankle of the supporting leg Task 5: one legged – opened eyes (left and right leg alternately) – free leg at 90° hip and knee flexion Task 6: one legged – open eyes provocation (left and right alternately) - free leg the height of the ankle of the supporting leg – displacement of the platform of 20mm in the x-Axis – provocation from medial 5 Balance 66 The order in which the tasks were performed was the same for all subjects and for all experiment sessions. Each task was performed for a maximum of 30 seconds and was repeated three times in a row. Between repetitions of identical trials, subjects had a 90 second rest and between the different trials 150 seconds in order to minimize the effects of fatigue. During the resting periods, subjects were sitting on a chair. The optimal performance was defined at a holding time of 30 seconds. When subjects completed this, the trial was ended. Time was stopped if subjects touched the ground with the free leg or had to grab the handrail and when they left the platform. The position of the supporting legs was standardized as much as possible. To be able to do so, a scale was mounted to the plate that indicated the mid point of the plate in both directions (Figure 5.3). For the two legged position, the foot was positioned with the midpoint of the length of the foot on the medial-lateral axis of the platform. The legs were ‘hip wide’ apart with each leg having the same distance from the anterior-posterior axis of the platform. Figure 5.3: Position on the ‘Posturomed®’ Platform for all two-legged tasks For all one-legged tasks, the foot was placed in the middle of the plate with reference to the anterior-posterior and the medial-lateral axis of the foot as well as of with the platform (Figure 5.4). The position of each subject was recorded and used again for all following measures. After the positioning of the foot, the measurements commenced. After taking the right position for the next task, the subjects had the possibility to stabilize their 5 Balance 67 position on the platform. When ready, the researcher would perform a countdown in order to get the subject’s attention to the experiment. Only with the beginning of the measurement, the subject would loosen the grip on the handrail and place the hands on the hips. This assured a repeatable position for the balance tests. Figure 5.4: Position on the ‘Posturomed®’ Platform for all one-legged tasks For the trials with closed eyes, the subjects used a blindfold in order to ensure the absence of vision for the complete task. In order to avoid injuries, a second person stood right beside the platform and helped the subject when he lost their balance. 5.2.3 Statistics The ability to stabilize body position on the ‘Posturomed®’ device was used to quantify the effect of bed rest as well as the combination of bed rest and vibration training on balance. The parameters were: o holding time of a certain position in seconds (s) o displacement of the platform per second in centimetres (cm) For the holding time, the mean of the three trials for each task were calculated, then pooled for all of the subjects and then compared using a t-test. 5 Balance 68 Displacement was measured by an accelerometer in mean distance of the sensor to the origin of the platform in time. Here an increase in displacement indicates a decrease in the ability to stabilize body position. Level of significance was reached at α = 5%. Thus, values were considered to be different when p < 0.05. Data analysis was performed using Statistica Softwear (StatsSoft, Version 7.0). Additionally, the correlation between the parameters ‘holding time’ and ‘displacement of the platform’ was analysed. The correlation between the two parameters, displacement and holding time, was calculated using the same mean values as previously stated for holding time and displacement. Correlation was calculated using the Pearson-Test. 5.2.4 Association with Data Loss For the measure of displacement, some data points were lost due to a crash of the computer system. This affected one session for two subjects. The missing data were replaced by the values of the familiarization measurement. An impact on the outcome of the results is not expected as this happened in the VBR 2 study phase and the subjects knew the ‘Posturomed®’ system by that time. Also, the affected subjects had very well developed balance ability and data analyses of the pre-bed rest values from the VBR 1 study phase did not show a learning effect for these two subjects. General effects on balance should not be affected as the lost trails only represent 60 data points out of 1960. Holding time has not been affected as a manual protocol for these values existed. 5.2.5 Malfunction of the Sensors of the ‘Posturomed®’ In 9 trials, displacement was not measured correctly in one of the two axes. The lost data were compensated with the following formula: Formula 1: (value of the measured axis) ∗ 2 5 Balance 5.3 69 Results 5.3.1 Holding Time For the analysis of holding time, the mean values of each task for all subjects were calculated and then pooled. Figure 5.5 shows the mean values of holding time for all subjects and all tasks. Figure 5.5: Mean holding time (± Standard deviation) for all subjects and all tasks (n=48) in seconds (s). Asterisk indicates a significant difference between the values (p = 0.01). During the control intervention, the holding time did not change compared to pre-bed rest values after 14 days of bed rest (Control: pre-bed rest: 25.8 ± 7.65 seconds / post-bed rest: 25.5 ± 7.98 seconds). When subjects received vibration training holding time decreased significantly from 27.0 ± 6.8 seconds to 25.6 ± 8.32 seconds (p = 0.01) The analysis of the individual tasks could indicate that not all tasks are affected by bed rest (see Table 5.2). Significant differences in balance performance were only detected in Task 4 ‘one-legged stand with closed eyes’ for the control (pre-bed rest 14.10 ± 7.15 s / post-bed rest: 11.33 ± 5.56 (p = 0.02)) and the vibration condition (pre-bed rest 16.71 ± 9.29 s / post-bed rest: 11.94 ± 8.30 (p = 0.02)). All subjects always completed fully the ‘two-legged stand’ task independently from visual control. Results did not change due to bed rest. For the ‘one-legged’ conditions, increasing standard deviations were noted. 5 Balance 70 Table 5.2: Mean holding time ± Standard deviation for all subjects (n=8) and the 6 different tasks. Values are shown for pre and post-bed rest during the control and the vibration training intervention. Grey marked boxes indicate significant changes from pre to postbedrest values for the different interventions (control: p = 0.02 / vibration: p = 0.02). Tasks 1 2 3 4 5 two legs open eyes two legs closed eyes one leg open eyes one leg closed eyes one leg high 6 provocation pre-HDT control post-HDT control pre-HDT vibration post-HDT vibration 30 ± 0 30 ± 0 30 ± 0 30 ± 0 30 ± 0 30 ± 0 30 ± 0 30 ± 0 27.73 ± 5.58 27.90 ± 3.58 29.40 ± 1.78 29.62 ± 1.45 14.10 ± 7.15 11.33 ± 5.56 16.71 ± 9.29 11.94 ± 8.30 29.87 ± 0.48 29.65 ± 1.29 27.35 ± 5.76 28.83 ± 4.27 30 ± 0 28.42 ± 4.09 28.90 ± 2.92 28.19 ± 4.65 5.3.2 Displacement of the Platform For the analysis of displacement of the platform, the mean values of each task for each subject were calculated and then pooled. Thus, one mean value for each subject per task went into the analysis. Figure 5.6 shows the mean values of displacement of the platform for all subjects and all tasks. During the control intervention, the displacement of the platform did not change from pre to post-bed rest values (control: pre-bed rest: 3.62 ± 3.87 cm / post-bed rest: 4.13 ± 4.74 cm (p = 0.054). When subjects received vibration training during the bed rest period, a significant increase in displacement of the platform of 22% was noticed (vibration: pre-bed rest: 3.05 ± 3.27 cm / post-bed rest: 3.71 ± 4.71 (p = 0.01). Analysis of the different tasks separately showed a significant difference in displacement from pre to post-bed rest values for the control and the vibration intervention (see Table 5.3) when performing ‘task 4 - one leg closed eyes’. No other significant changes were found when analysing the different tasks. 5 Balance 71 Figure 5.6: Mean holding time (±Standard deviation) for all subjects and all tasks (n = 48) in seconds (s). Asterisks indicate a significant difference between the values. Table 5.3: Mean displacement ± Standard deviation in cm/s for all subjects (n=8) and the 6 different tasks. Values are shown for pre and post-bed rest during the control and the vibration training intervention. Grey marked boxes indicate significant changes from pre to post-bed rest values for the different interventions (control: p = 0.03 / vibration: p = 0.02) Tasks two legs 1 pre-HDT control post-HDT control pre-HDT vibration post-HDT vibration 0.32 ± 0.07 0.36 ± 0.08 0.32 ± 0.06 0.43 ± 0.1 0.47 ± 0.21 0.38 ± 0.11 0.50 ± 0.25 0.62 ± 0.27 2.37 ± 2.01 2.33 ± 1.64 1.93 ± 1.17 1.82 ± 0.92 9.65 ± 3.19 11.68 ± 2.89 8.07 ± 3.60 10.35 ± 4.37 1.88 ± 0.64 1.91 ± 0.60 1.81 ± 0.86 2.02 ± 0.83 3.84 ± 2.97 4.38 ± 4.62 3.04 ± 1.85 3.84 ± 3.12 open eyes two legs 2 closed eyes one leg 3 open eyes one leg 4 closed eyes one leg 5 high 6 provocation 5 Balance 72 5.3.3 Correlation of the Parameters Displacement and Holding Time The calculation of a correlation between the two parameters, displacement (cm) and holding time (s) shows a high negative correlation for each of the measuring points (Table 5.4). Table 5.4: Correlation of displacement pro (s) in (cm) and holding time (s) for all subjects and all tasks. Control Control Vibration Vibration Pre-bed rest Post-bed Rest Pre-bed rest Post-bed Rest -0.93 -0.86 -0.87 -0.92 Correlation displacement / holding time 5 Balance 5.4 73 Discussion The results did not confirm the first hypothesis that 14-days of 6°-HDT bed rest would negatively affect the ability to stabilize body position as measured with the Posturomed®’ device. Contrary to our expectations, 14-days of immobilization did not lead to negative effects on holding time and displacement of the platform. The predicted correlation between the parameters displacement of the platform and holding time of the tasks were confirmed. Balance ability in the VBR-Study was measured with the Posturomed® using the parameters holding time and displacement of the platform’. The Posturomed® measures a very complex process on a systemic level. Although many components contribute to the ability to keep balance, the Posturomed® only gives information about the overall balance performance level of a subject. Negative effects of a measure on some of the contributors to ‘balance ability’ may be compensated by other components that are less affected. The sum of the activities of all contributors may still result in the same total balance performance. This could be due to the relatively short period of bed rest in addition to the fact that healthy subject were investigated. A more detailed analysis, for example, on receptor activity or the different reflex loops may have given another picture. Figure 5.7: Organs and tissues contributing to the ability to keep a balanced body position. In this experiment, it is only possible to estimate the effects of bed rest on the contributing organs and tissues and how much this may have affected the result of our study in comparing the data with other research literature. The otolith-ocular reflex and thus the ocular counter-rolling certainly does have a major impact on the ability to keep balance (Moore et al., 2001). This is supported by the investigation of a significant decrease in the performance level for task 4 – 5 Balance 74 one leg - closed eyes from pre-bed rest to post-bed rest values during the control intervention. Vision serves the subject some reliability that may counteract physical weaknesses. If the visual control is deactivated, the physical abilities get more important and weaknesses may show up that have not been noticed before. It would be interesting and important to actually measure how the different factors of balance performance contributed to the results. However, this was not the main task of this study and it was outside the scope of our methodology. In this context, it should also be noted that the level of difficulty of the separate tasks may not have been high enough. To fulfill a motor task, it needs certain physical requirements. If an adequate level of, for example, fitness is achieved, one can perform this task. But to be able to perform task 1 – two legged open eyes, the motor capabilities are unlikely to be exhausted, meaning the capacity is much higher than the requirements. In other words, the task is very easy for the subject. On the other hand, if the task is so much below the actual capabilities, the capacity to perform a task can become smaller; but on the performance level, this would not be noticed, particularly with the methods used in this study. The performance of the easy task does not change but the potential and ability to perform more difficult tasks decreases. In this study, the duration of the immobilization may not have been sufficient to affect clearly balance performance so that it could have been adequately examined with our set of test level. Healthy subjects who were still allowed to move within the given bed rest requirements, were investigated. Consequently, our subjects were more mobile in bed compared to injured or disabled patients for whom movement may be completely reduced, for example, due to pain, bandage or casting. Additionally, subjects walked a defined distance, twice daily, to the training room and back. However, this procedure was important in order to be able to respond to our hypothesis. Nevertheless, it may have led to a slower decrease in balance ability as the body still received postural input twice a day. The conditions of the bed rest study were very controlled and most importantly, the subjects received a normo-caloric diet for the activity conditions they lived in during the bed rest period (see Chapter 3 - General Methods). This may have contributed to the observed effects on skeletal muscle that were much less than expected (see Chapter 1 - Muscle Performance). As mentioned earlier, there is a strong relationship between muscle atrophy and balance performance (Froböse et al., 2003; Wilke et al., 2003). Decreases in skeletal muscle mass were observed in this study; however, this did not affect muscle performance as much as expected. 5 Balance 75 Muscle performance does play a key role in balance performance and this may explain the unchanged level of balance performance. Our second hypothesis, that vibration training during 14-days HDT bed rest can minimize the negative effects of immobilization on balance performance, was also not confirmed. Holding time as well as displacement of the platform, showed deterioration after 14-days of HDT-bed rest with vibration training rather than an improvement in this area. Our first hypothesis that bed rest would affect balance performance was not supported by the results. A clearly negative effect of bed rest on balance performance that could be counteracted by vibration training has not been found. Moreover, vibration training even deteriorated the effect of bed rest on holding time as well as displacement of the platform (Jansen, 2006). This result is surprising given that many studies suggested a positive effect of vibration training on balance (Bautmans et al., 2005; Bogaerts et al., 2006; Brunetti et al., 2006; Bruyere et al., 2005; Cheung et al., 2003; Cheung et al., 2007; Gusi et al., 2006; Kawanabe et al., 2007). However, with durations from 6 weeks up to 12 months of time for treatment in these studies, they were a lot longer compared to our study. More importantly, most elderly people (average age > 60) were investigated in previous studies compared to young, healthy subjects in our study. Since the sensory motor system showed a deterioration with aging at different levels of the sensory and motor systems (Shaffer and Harrison, 2007; Shkuratova et al., 2004), it seems likely that the age of the subjects has an impact on the outcome of a study. Presumably, subjects in the previous studies started at a much lower balance performance level than our subjects. With lower baseline performance levels and longer periods of vibration training, it is more likely to improve balance performance than under the conditions of the VBR-study. As discussed earlier, only 14 days of bed rest may not have been long enough to affect significantly the balance performance in the control group and to result in a significant compensatory training effect in the vibration group. A study of Davis et al. (1997) also showed no effect after 5 days of bed rest due to a training intervention compared to the control group (Davis et al., 1997) which supports the finding that duration of the bed rest and intensity of the treatment were not sufficient to cause a potential improvement for the vibration training group. The vibration training did not just fail to counteract a bed rest effect, but it decreased the level of balance performance as well. The measure of balance performance was performed right after subjects finalized the bed rest period with the tilt table experiment. The time point could be called ‘semi-acute’ as the last vibration training session had been performed the day before. Thus, an adequate time for adaptation 5 Balance 76 was not given. A follow up measure would be desirable and should be applied in future studies, but it is not available for the VRB-Study. The sinusoidal signal from the vibration platform has been one of the few sensory input signals the subjects received during the bed rest period. Subjects were barefooted and stood on the vibration platform with the whole sole of the foot. Especially for the mechano-receptors that are located in the lower limb and under the sole of the foot, which were closest to the vibration source, the vibration signal is a very demanding input. The decreased balance ability could be the result of an irritation or adaptation of the respective receptors to the vibration signal. This is especially true for the Meissner corpuscles and the Pacinian corpuscles which are located in the skin and are specifically sensitive to vibrations. These mechano receptors do not typically belong to the proprioceptors but belong more to the cutaneous receptors (Lundy-Eckman, 2002; Shaffer and Harrison, 2007). However, their input is very important for the sensing of joint position as well as movement. For the receptors under the sole of the foot, it could be shown that these receptors give information about the site and the force of weight-bearing activities and they also can influence muscle activity of the lower extremity (Burke et al., 1989; Kennedy and Inglis, 2002; Lundy-Eckman, 2002; Perry, 2006; Robbins et al., 1995; Shaffer and Harrison, 2007). Since they are very sensitive to an adaptation in response to vibration training, it is very likely and may be the reason for the decrease in balance ability after the application during the bed rest period. However, due to our methods, we can only speculate about this process. Longer studies may show different results because the lower the level of balance performance becomes in response to immobilization the more the effect of a vibration training application dominates over the effect on the cutaneous receptors. Other sensory organs, like the Golgi-Tendon organ or the muscle spindles, may show the same effect of adaptation to the vibration training intervention. Muscle spindles are very sensitive to stretch of the muscle and play an important role in reflexive and voluntary movements as they provide afferent input to the central nervous system (Prochazka, 1981; Shaffer and Harrison, 2007). As muscle spindles are sensitive to aging (Shaffer and Harrison, 2007; Swash and Fox, 1972) and immobilization (Anderson et al., 1999; Jozsa et al., 1988; Rosant et al., 2006) it is likely that they are also sensitive to overload due to vibration stimulus during an otherwise passive situation. Consequently, this could lead to deterioration when performing the balance testing immediately after completing the bed rest period. As expected, there is a high negative correlation between the two parameters displacement and holding time. It is not surprising that with an increasing 5 Balance 77 displacement of the platform, the holding time decreases. Thus, using the Posturomed® device, the ability to stabilize the platform is well predictable for the holding time to achieve a task and vice versa. 5.4.1 Limitations of the Design 5.4.1.1 Influence of Learning Effects A great effort has been made to minimize the impact of learning effects on the outcome measures (see 5.2.2). The balance performance level was heterogeneous in the population of this study that made the practice session even more important, especially for the subjects with a lower level of balance performance. Familiarization and practice clearly minimized the learning effect. However, it could not avoid differences in the performance levels of the subjects and thus in the sensibility to respond with a change in balance performance due to bed rest. The heterogeneous population may also have caused the high standard deviations observed, especially in the one legged tasks. For future studies, an additional practise session should be performed. Data analysis showed that the holding time of a certain position was more sensitive for learning effects than the displacement of the platform. 5.4.1.2 Order of the Tasks The 1-6 order of the tasks was intentionally chosen by the investigators. The reason for this was an increase in the level of difficulty so that the most difficult task was positioned at the end of the experimental session. Only during the performance of the experiment did it turn out that the subjects assessed the level of difficulty differently. Task 4 ‘one leg, closed eyes’ was considered the most difficult task as the visual control was missing. It was decided, however, to retain with the same order for the rest of the study and for all subjects. Thus, if fatigue had an impact on the balance performance of the subjects, it was the same for all subjects. The separate analyses of the different tasks showed that ‘task 4’ in fact was the only one that showed significant changes due to immobilization which was probably due to the fact that it was the most demanding task. 5.4.1.3 Control Group The decision to allow the subjects to train in an upright position was chosen intentionally in order to get the highest degree of control of the training intervention 5 Balance 78 (see chapter 3 - General Methods). However, it may have had an impact on the results for the pre and post-bed rest values that reduced the difference in response between the control and the vibration intervention group. 5.4.2 Conclusion and Future Work In conclusion, both of the hypotheses could not be confirmed. However, the goal to measure the effect of bed rest on balance with the Posturomed® was achieved and well tolerated by the subjects. The results suggest that vibration training may be a very demanding task for the cutaneous receptors as well as muscle spindles and other proprioceptors. This aspect needs further investigation within the context of vibration training. The length of bed rest that was under very well controlled conditions used in this study may not have been sufficient to significantly affect balance. Clearly, if vibration training is to be applied over a long duration in space flight, the effects of vibration training on all factors influencing the stability of body position should be further investigated in order to be able to predict the range of effects on different structures in the human body that can occur and to determine the advantages and disadvantages of a training method. 6 Cartilage Health 79 6 Cartilage Health 6.1 Specific Background Articular cartilage in synovial joints serves a variety of functions which include providing joint congruency, transferring and distributing forces, and allowing joint movement. A healthy biological and mechanical environment for cartilage is the prerequisite for proper joint function. Typically, a change in the biological and/or mechanical environment for cartilage leads to cartilage degeneration or osteoarthritis. The most common location for osteoarthritis is the knee (Neame et al., 2004). While the role of mechanobiological factors for healthy cartilage development and maintenance have received much attention (Carter and Wong, 1988a; Wong et al., 1999; Wong and Carter, 1988) the effects of immobilization or partial weight bearing after injuries and the effects of space flight on cartilage biology and morphology in man are largely unknown. 6.1.1 Cartilage Morphology and Loading Mechanobiological factors cause, throughout life, changes in articular cartilage thickness distributions or cartilage morphology in a joint (Carter and Beaupre, 2001). Cartilage morphology, for example when cartilage degrades and thus becomes thinner, may be indicative of degenerative processes of cartilage (Phan et al., 2005). Healthy articular cartilage tends to be thickest in joints, such as the knees, that experience high forces. In addition, side differences in muscle cross sectional are positively correlated with side differences in articular cartilage morphology (Eckstein et al., 2002b). A recent study (Andriacchi et al., 2004) showed, that for healthy knees, the ratio of medial to lateral cartilage is greater in individuals who have a larger peak knee adduction moment during walking, suggesting that cartilage is thicker in areas where the load is greater. These results support the animal studies (Haapala et al., 1996; Haapala et al., 1999; Haapala et al., 2000; Jortikka et al., 1997; Jurvelin et al., 1986; Kiviranta et al., 1988a; Kiviranta et al., 1994) where articular cartilage increased in thickness by up to 19 to 23% (Kiviranta et al., 1988b) when high mechanical loads were applied. An increase in cartilage thickness with exposure to higher loads may be off-set by a greater cartilage surface that may be caused by high physical activity during growth (Eckstein et al., 2002a; Muhlbauer et al., 2000). Changes in tibio-femoral cartilage thickness are not dose dependent suggesting that adult human cartilage properties may not be sensitive or improved with training (Eckstein et al., 2005). 6 Cartilage Health 80 Disuse induced changes in cartilage morphology and biology could be shown in previous studies on animals as well as humans. A study on young beagle dogs found decreases in proteoglycan concentration and compressive stiffness after 11 weeks of immobilization (Haapala et al., 2000; Jurvelin et al., 1986; Kiviranta et al., 1988a). In this study, the right hind limbs of the dogs were immobilized at 90° flexion of the knee and ankle joint with a fibreglass cast. Further investigations of the same group showed that the immobilization induced cartilage softening was not fully restorable (Haapala et al., 1999). In a different study, canine knees were immobilized with a sling causing mechanical unloading but still allowing minimum motion in the joint (Setton et al., 1997). The investigators found no changes in proteoglycan and collagen content, cartilage stiffness or cartilage thickness (Setton et al., 1997). The discrepancy of these results may have been due to the fact that the type of immobilization played a role in the potential of the cartilage to recover (Behrens et al., 1989). Only a few studies (Eckstein et al., 2002a; Hinterwimmer et al., 2004; Muhlbauer et al., 2000; Vanwanseele et al., 2002; Vanwanseele et al., 2003) have investigated the influence of mechanical unloading on articular cartilage in humans. For instance, in paraplegic patients, cartilage thinning of up to 25% after 24 months has been observed (Vanwanseele et al., 2003). Hinterwimmer et al. (Hinterwimmer et al., 2004) investigated the effect of 7 weeks of partial load bearing on articular cartilage morphology changes in all knee compartments. Changes in articular cartilage thickness for the different compartments ranged from -2.9 ± 3.2 % for the patella to -6.6 ± 4.9% for the medial tibia. 6.1.2 Cartilage Oligometric Matrix Protein Cartilage oligometric matrix protein (COMP) is a structural protein primarily found in cartilage (Hedbom et al., 1992). COMP may also play a role in stabilizing the extracellular matrix through its interaction with collagen fibrils and other matrix components (Johnson et al., 2004; Mann et al., 2004). Changes in serum COMP concentration have been associated with cartilage degradation (Neidhart et al., 1997) and may be an indicator of cartilage catabolism (Jordan, 2005). Serum COMP concentrations are elevated in patients with knee osteoarthritis (Clark et al., 1999) and rheumatoid arthritis (Forslind et al., 1992). Cartilage, like other biological tissues including skeletal muscle and bone, is sensitive to loading and disuse (Johnson, 1998; Smith et al., 1992b). For instance, elevated serum COMP concentrations have been reported after a moderate walking exercise in healthy adults (Mundermann et al., 2005) and after extensive running exercise in athletes (Neidhart et al., 2000). Thus, serum COMP concentration appears to be sensitive to 6 Cartilage Health 81 physiological loading. Similarly, it has been suggested (Carter and Wong, 1988b; Wong and Carter, 1988) that cyclic mechanical loading may play an important role in regulating metabolic processes associated with the development, remodelling and disease of biological tissues, including cartilage. In particular, the turnover of COMP fragments may be an important mechanism for the regulation of tissue synthesis and degradation (Giannoni et al., 2003; Wong et al., 1999). The increasing number of patients with degenerative cartilage diseases, as well as, for example, the prospect of a possible flight to Mars with an possible duration of two to three years emphasizes the need for further research in the field of cartilage health and mechanical unloading. One model for simulating physiological effects of a microgravity environment on the human body on earth is bed rest in a 6°-headdown-tilt (HDT) position (Kakurin et al., 1976). 6.1.3 Vibration Training In an attempt to increase the efficiency of strength training that may affect all tissues of the musculoskeletal system, in the past decade vibration training became very popular as a complement to regular strength training (Jordan et al., 2005). During whole body vibration training, the subject performs isometric or dynamic exercises on a vibrating plate. Vibration frequencies between 15 Hz and 90Hz have been used to either achieve adaptations in muscle or bone muscle (Issurin, 2005; Rubin et al., 2002a). For instance, high frequency low amplitude vibration training has been shown to increase osteogenesis of bone in animals (Rubin et al., 2001) and humans (Rubin et al., 2002a; Rubin et al., 2002b). Thus, vibration training may have the potential of reducing negative effects of unloading on biological tissues including cartilage. 6.1.4 Purpose of the Study and Hypotheses There is still a controversial debate whether articular cartilage is sensitive to unloading and also if articular cartilage is able to recover after degradation. Also the biological response of articular cartilage in healthy subjects to relatively short term unloading during bed rest induced immobilization or spaceflight is still unknown. Similarly, it is not known if possible effects of unloading on articular cartilage can be avoided using a simple and time-efficient exercise regiment. Therefore, the purpose of this study was to assess the influence of a vibration training intervention on the morphological and biological changes on cartilage associated with immobilization. To achieve this purpose the following hypotheses were explored: 6 Cartilage Health a) 82 14-days of head down tilt bed rest will lead to a reduction in cartilage thickness loss, b) Vibration training will slow down or prevent the reduction in cartilage thickness, c) 14-days of head down tilt bed rest will lead to a reduction in serum COMP concentrations, d) Vibration training will slow down or prevent the reduction in serum COMP concentrations. 6 Cartilage Health 6.2 83 Specific Methods 6.2.1 MR-Imaging The left knee of each subject was examined using a 1.5 Tesla magnetic resonance imaging (MRI) scanner (Siemens Sonata, Erlangen, Germany). MRI data collection was performed at the Cardio-MR Praxis, Krankenhaus Porz, Cologne, Germany. Articular cartilage of the tibio-femoral joint was imaged in the sagittal plane before and after the intervention or control phases. Images were taken on the last day (day -1) of the adaptation period prior to bed rest and on day R1 in the recovery period after the bed rest. Subjects walked a defined distance to the MR praxis, controlled by the activity monitor. Imaging was performed at an in-plane resolution of 0.35 mm x 0.35 mm, slice thickness 2mm, and an image matrix of 448 x 512 pixels. After data collection, all images were segmented by one of the investigators. The investigator was blinded to the order of the image acquisition (pre-HDT, post-HDT) and also to the intervention (vibration training, control intervention). 6.2.2 Three-dimensional (3D) Cartilage Model Cartilage in each slice of the MR images was segmented using a B-Spline Snake algorithm with manual correction built into our custom software (Koo et al., 2005). Once a user draws an initial boundary, the algorithm moves the boundary close to the edges of cartilage. The MR images do not always have consistent brightness, thus manual correction was required. The cartilage boundaries from all slices in a MR image set were combined to create a 3D cartilage model using a volume rendering technique (Koo et al., 2005), which fills the space between boundaries obtained from adjacent slices and creates a polygonal surface model. The cartilage model was divided into an articulating surface and cartilage-bone interface surface to calculate cartilage thickness. For each point on the articulating surface, the closest point on the cartilage-bone interface surface was found and the distance between the two points was color-coded on the two points. The accuracy of the cartilage thickness measurement using this method was verified in our previous study (Koo et al., 2005). The cartilage model building process was performed by a single observer to increase the reproducibility of the process. The coefficient of variation (= standard deviation / mean * 100) of intra-observer reproducibility in measuring average cartilage thickness of a weight bearing region over five repetitions was 1.6%. 6 Cartilage Health 84 6.2.3 Cartilage Thickness Measurement The tibio-femoral contact areas in the femoral cartilage were divided into three functional weight bearing regions for each condyle based on the knee flexion angle during walking (Koo et al., 2005). The knee is flexed from 0 to 30 and 0 to 60 degrees during stance and swing phases of normal walking respectively. The flexion angle can be less than 0 in the case of knee hyper extension. Thus we defined anterior, middle and posterior weight bearing regions which match the tibio-femoral contact regions at -30° to 0°, 0° to 30° and 30° to 60° of knee flexion angles respectively (Figure 1). Average thickness was calculated for the load bearing anterior, middle and posterior regions of the femur and the anterior and posterior region of the tibia. Medial and lateral articulating surface of femur and tibia were analysed. 6.2.4 Blood Fasting blood samples were drawn at 7.00 am on days -3 and -1 in the adaptation period, days 2, 6, 8, 11, 13, 14 of the intervention period and on day R2, R3 and R5 of the recovery period (Table 1). Blood was drawn by medical doctors using a short catheter in serum monovettes (Sarstedt, Germany) from a antecubital vein. 150 µl serum was aliquotted into Eppendorf tubes and frozen at -80°C until analysis. Serum COMP concentration was analysed using a commercial enzyme-linked immunosorbent assay (COMP® ELISA; AnaMar Medical AB, Lund Sweden). Analysis was performed in duplicate. All samples of any subject of both study phases were analysed on plates from the same batch of COMP® ELISAs. In addition, all samples of any subjects were analysed on the same plate to avoid differences in serum COMP concentration due to inter-assay variation. 6.2.5 Statistical Analysis Statistical analyses were performed using STATISTICA software (StatSoft, Inc., Tulsa, USA). All results are shown as means ± SD. Differences in serum COMP concentrations between days and phases were detected using repeated measure analysis of variance (ANOVA) with phase as factor. Similarly, differences in cartilage thickness before and after intervention and between phases were detected using repeated measures ANOVA with phase as factor. 6 Cartilage Health 6.3 85 Results 6.3.1 Cartilage Thickness Changes in average and maximum cartilage thickness after 14 day of 6°-HDT bed rest were observed for the tibia but not for the lateral and medial compartments of the femur (Table 6.1). Table 6.1: Average values and changes in mean and maximum thickness (± SD) for the mechanically loaded regions of articular cartilage in the knee pre and post 14 days of HDTbed rest (n=8).’d -1’ stands for day -1 in the recovery phase, d R1 for the first day in the recovery phase. The asterisk indicates p-values < 0.05. Compartment Maximum Thickness Mean Thickness [mm] [mm] Control Vibration Control Vibration Tibia pre-HDT (d -1) 5.02 ± 1.18 4.18 ± 1.03 3.08 ± 0.60 2.66 ± 0.45 post-HDT (d R1) 4.29 ± 1.25 5.25 ± 1.21 2.82 ± 0.60 3.24 ± 0.63 %change -14.57* 26.61* -8.3* 21.91* pre-HDT (d -1) 3.70 ± 0.50 3.91 ± 0.52 2.37 ± 0.40 2.50 ± 0.24 post-HDT (d R1) 3.90 ± 0.74 3.97 ± 0.46 2.41 ± 0.30 2.52 ± 0.25 %change 5.32 1.58 -2.16 -5.90 pre-HDT (d -1) 3.73 ± 0.51 3.50 ± 0.86 2.36 ± 0.43 2.28 ± 0.22 post-HDT (d R1) 3.84 ± 0.50 3.40 ± 0.58 2.44 ± 0.32 2.30 ± 0.23 %change 2.70 -2.50 3.70 -2.51 Lateral Femur Medial Femur The rate of change in average and maximum cartilage thickness did not differ for the medial and the lateral compartment as well as for the anterior and posterior region in each compartment of the tibia for both phases (CON and VIB) so that all values for the tibia were analysed as one compartment. When subjects received the control intervention, average and maximum cartilage thickness decreased significantly (average thickness: p = 0.025; maximum thickness: =0.015) after 14 days of bed rest (maximum thickness: %-change = -14.57% (Figure 6.1), average thickness: %- 6 Cartilage Health 86 change -8.3 %). The opposite result was observed for the vibration training condition. Average and maximum thickness in the tibial cartilage increased significantly by 26.61% (maximum thickness) and 21.91% (average thickness). Values in the lateral as well as the medial femoral cartilage for anterior, middle and posterior regions did not show significant differences as a result of bed rest or the training intervention. 7 cartilage thickness [mm] 6 * * 5 pre post 4 3 2 1 0 control vibration intervention Figure 6.1: Absolute changes of cartilage thickness in the tibia from pre- to post-HDT-bed rest for the control and the vibration condition (n = 8). Data are shown as mean of all subjects with SD. *: p < 0.05. 6.3.2 Serum COMP Concentration On adaptation day -3, mean serum COMP concentration was 7.02 ± 1.12 U/l for the control phase (CON) and 7.23 ± 1.15 U/L for the intervention phase (VIB). With 6.80 ± 1.41 U/L (CON) and 6.90 ± 0.95 U/L (VIB) at day -1 prior to bed rest, serum COMP concentrations were stable for the baseline measurements. Serum COMP concentration was in the range of normal distribution for healthy subjects (AnaMar Medical AB, 2003).The first blood samples after 24 hours of 6°-HDT intervention showed a significant decrease in serum COMP levels (CON: 5.80 ± 0.84 U/L; VIB: 6.20 ± 0.75 U/L (p = 0.022)) (Figure 6.2). Values decreased on average by 14.8% 6 Cartilage Health 87 when subjects received the control condition and by 10.1% for the vibration training condition. However, there was no statistical difference in the response of serum COMP concentration between the control and the vibration training condition. During the 14-day 6°-HDT bed rest period the values stayed stable at lower levels for both groups. No difference in the adaptation of the serum COMP concentration due to the training intervention could be observed throughout the period of bed rest. Serum COMP concentration for both phases returned to baseline levels after subjects were mobile again (CON: 6.78 ± 0.91 U/L (+ 28.6%), VIB: 6.96 ± 0.94 U/L (+ 26%): (p < 0.001)) and remained stable at higher levels for the recovery period. 9 COMP (U/L) 8 * * HDT VIB HDT CON 7 6 5 4 0 -3 -1 2 6 8 11 14 R2 R3 R5 days Figure 6.2: Average changes in serum COMP concentration in response to 6°-HDT bed rest and vibration training (n=8). Serum COMP concentration decreased significantly (p = 0.022) after 24h of bed rest and returned to baseline levels after subjects were mobile again (p = 0.001). 6 Cartilage Health 6.4 88 Discussion The data show that 14-days of HDT bed rest lead to a significant loss in cartilage thickness in the tibia as well as systemic serum COMP concentration. The applied vibration training protocol appears to prevent the loss of cartilage thickness and, the reduction in serum COMP concentration could not be prevented. This is the first study to investigate the adaptation of articular cartilage in the knee to a short period of immobilization in healthy young subjects. We hypothesized that a 14 day bed rest immobilization will lead to a reduction in cartilage thickness and serum COMP concentration and secondly, that vibration training may be beneficial to prevent a reduction in cartilage thickness and serum COMP concentration. Our results show that, after only 14 days of immobilization through bed rest, cartilage thinning at the knee can be observed. When subjects received vibration training twice a day, cartilage thickness at the knee increased. Cartilage thinning in our study was only significant in the tibia compared to previous studies (Hinterwimmer et al., 2004; Vanwanseele et al., 2002) that reported changes in all cartilage compartments at the knee. However, Hinterwimmer et al. (Hinterwimmer et al., 2004) and Vanwanseele et al. (Vanwanseele et al., 2002) also found that changes of articular cartilage thickness were more pronounced in the tibia than in the femur. Different results for both the tibia and the femur are not surprising considering that, due to the anatomy of the knee joint, the load bearing area of the tibial plateau is much smaller compared to the femur head for knee flexion angles between 0° and 60°. This contributes to higher stress rates in the tibia when the joint is mechanically loaded and may also cause a stronger response of the tibia to unloading. In the current study, cartilage thinning was similar for the medial and lateral tibia compartments in contrast to previous studies (Hinterwimmer et al., 2004; Vanwanseele et al., 2002). A possible explanation may be the short amount of time that our subjects were exposed to immobilization compared to those in previous studies. This time period may not have been long enough to develop different adaptations in different compartments. The subjects in this study had no history of knee injury and no cartilage lesions were detected in the MR images. Subjects were ‘mobile’ during the bed rest period. This meant that they were allowed to move their joints and to turn around to lie on their back, front or on their side as long as they did not leave the 6°-HDT position. In addition, subjects walked a defined path to the training room leading to cyclic loading of cartilage possibly stimulating metabolic activity. Patients who are 6 Cartilage Health 89 immobile after injury or surgery are usually under pain and thus move their joints even less than our subjects. It may be that changes in cartilage thickness in these patients would be even more pronounced. Because cartilage is an avascular, aneural and alymphatic tissue, mechanical stimulation is, besides diffusion, the only signal pathway from the periphery to the chondrocytes. The extracellular matrix functions as the signal transmitter which transfers mechanical signals to the chondrocytes. In response, chondrocytes change their metabolic activity (Martinek, 2003). It has also been shown previously, that unloading cartilage changes proteoglycan synthesis (Gray et al., 1988) resulting in altered mechanical properties of the tissue. Proteoglycans are negatively charged and therefore exert a large swelling pressure that causes tensile stress on the surrounding collagen network (Maroudas, 1976). If unloading of a joint can lead to changes in proteoglycan content, this may result in different hydration of cartilage. Thus, the measured decrease in cartilage thickness for the control condition and the increase for the vibration training intervention may not necessarily reflect a loss in cartilage tissue but a change in the mechanical properties of cartilage, due to an altered hydrostatic pressure. However, the imaging technique used in this study only detects quantitative changes in cartilage thickness and provides no information about the quality of the cartilage tissue. The mean and maximal thicknesses of the knee cartilage were quantified from MR images. They were taken in the sagittal plane, which did not allow for the accurate segmentation of the marginal areas. Additionally, we did not determine cartilage thickness of the patella. In contrast to previous studies (Hinterwimmer et al., 2004; Muhlbauer et al., 2000; Vanwanseele et al., 2002) that investigated changes in cartilage thickness over the entire surface under various conditions, we chose to measure cartilage thickness only in the load-bearing regions of articular cartilage. Therefore, our technique of using sagittal plane images was appropriate. In activities of daily living, the flexion angle of the tibio-femoral joint ranges between 0° and 60°. This corresponds to certain regions of the cartilage surface that are more frequently in contact with the congruent joint surface than others. Most likely, regions that are often more exposed to mechanical loading in every day life are more sensitive to unloading than regions that are generally not exposed to loading. This phenomenon can be compared with bone mineral content in mechanically loaded bones as compared, for example, to arm or shoulder bones. Loss in bone mineral content, due to unloading, is more pronounced in bones that are usually exposed to mechanical loading (Uebelhart et al., 2000). Similarly, for articular cartilage, a greater response to unloading in cartilage regions that are loaded during normal 6 Cartilage Health 90 joint motions than in normally unloaded regions may be expected. If usually loaded regions are more sensitive to unloading, then this may explain the greater range of change in mean cartilage thickness in our study compared to previous studies (Hinterwimmer et al., 2004; Vanwanseele et al., 2002). The results of this study show that a short term bed rest at 6°-HDT results in a reduction in serum COMP concentration within less than two days indicating that COMP is sensitive to unloading. One possible explanation for this reduction in serum COMP concentration is a decreased diffusion of COMP molecules from the cartilage into serum due to a lack of exposure of the joint to cyclic movement and loading. This possibility is supported by the fact that serum COMP concentrations returned to baseline within 24 hours following bed rest. Previous studies also found the sensitivity of COMP to mechanical loading (Jortikka et al., 1997; Neidhart et al., 2000; Wong et al., 1999). Our results support findings in marathon runners (Neidhart et al., 2000) and healthy subjects after walking exercises (Mundermann et al., 2005) who both found increases in serum COMP concentration in healthy subjects after exercise and thus stated the sensitivity of COMP to mechanical loading. This would lead to the conclusion that unloading should also affect serum COMP concentration. With our results, we could show deceases of serum COMP in the absence of joint loading. Another possible explanation for the reduction in serum COMP concentration during bed rest is a change in cartilage metabolism in response to the lack of mechanical stimulus during this period. Wong et al. (Wong et al., 1999) earlier reported a cyclic compression in vitro results in an up-regulation of protein synthesis. They stated that chondrocytes had the ability to sense stress or strain in the extracellular environment that resulted in an alteration of the expression of matrix proteins. Moving the knee joint causes hydrostatic stress and strain within the cartilage tissue of the knee joint. During our bed rest study, movement of the joint was reduced to a minimum due to the immobilization. Consequently, stress and strain in knee cartilage was likely to be reduced that possibly lead to a slower metabolism and thus reduce the turn-over of COMP. The vibration training intervention did not have a different effect on serum COMP concentration than the control intervention. Despite its benefits for general physical conditioning (Cardinale and Wakeling, 2005), the vibration training intervention used in this study with the goal to avoid the effects of prolonged bed rest may not have been sufficient in magnitude and/or duration to cause any significant changes in serum COMP concentration compared to the control intervention. 6 Cartilage Health 91 Scientific investigations of the effects of vibration training in a controlled study design are rare. The physiological response mechanisms caused by vibration training are largely unknown. The current study was a first attempt in quantifying the effect of arbitrary vibration training on cartilage in vivo. Secondly, different biological tissues, including cartilage, bone, muscle, ligaments, and tendons, may respond differently to the various combinations of vibration frequency, amplitude, training duration, and number of vibration bouts and thus, a training regime that is beneficial to muscle may not affect COMP turnover. Another aspect may be that the effect of immobilization on serum COMP concentration is greater than a possible effect of vibration training to counteract this effect. This may be caused by the amount of cartilage that is affected by bed rest compared to articular cartilage that is affected by the vibration training. Therefore, possibly only a more demanding training protocol would lead to changes in serum COMP concentrations systemically measured in blood. Vibration training had an effect on cartilage thickness but not on serum COMP concentrations. This result is not necessarily controversial. It may well be that the decrease in serum COMP concentration was caused by reduced diffusion of COMP molecules into the blood due to no movement of the joint. Cartilage thickness on the other hand, was maintained due to a mechanical stimulus that is load dependent. Thus thickness maintenance may not require flexion-extension movement. In summary, the results of this study suggest that articular cartilage thickness is sensitive to unloading and vibration training may be a potent countermeasure against these effects. Future research should strive to reveal the physiological processes that lead to the results that have been observed in this study. Additionally, the potential of the recovery of cartilage thinning in man after confined immobilization is still unknown. Serum COMP concentration is sensitive to unloading during bed rest. While COMP is a structural protein that reflects the state of cartilage, future research should investigate the effect of unloading on cartilage metabolism with the ultimate goal to minimize negative effects of bed rest or other models of unloading, such as space flight, on cartilage health. Understanding and quantifying the mechanical response of articular cartilage to its physical environment in healthy subjects may help to develop countermeasures to prevent cartilage thinning after prolonged bed rest due to illness or surgery. Until countermeasures have been developed, cartilage health has to be considered when patients start to load their joints again after mid-term or long-term bed rest and for astronauts upon their return to earth after a lengthy space flight. 7 General Discussion 92 7 General Discussion The general purpose of the Vibration-Bed-Rest-Study was to investigate the effects of 14-days of 6°-head-down-tilt bed rest on the human body in an integrative approach and to test whether vibration training could counteract the effects of immobilization on different systems and tissues of the human body. The results should provide a recommendation whether vibration training may serve as an appropriate countermeasure in the scope of space flight. Although HDT bed rest is a well established model to simulate the physiological effects of microgravity, the comparability of the population of students we examined in the VBR-Study with the population of astronauts may be difficult. These two populations may differ, for instance, in age and physical fitness, which would both impact the responsiveness to training. We are well aware of the differences of these two populations; however the problem cannot be resolved. Thus, the here presented results of the VBR-Study represent the effects investigated in our group of subjects. However, one should be aware of the earlier described constraints of inferential statistics (see chapter 3.8 - General Statistics). The transfer of the results into the application in space should only be conducted with the given limitations. The first hypothesis that 14 days of HDT would lead to a general deconditioning of the human body could not, in general, be confirmed for all physiological parameters examined in this thesis. A decrease in muscle performance was only given for the MVC and power of the knee flexors, whereas the extensors were not significantly affected. As discussed in chapter 4, there may be several reasons. Most importantly, subjects had different fitness levels prior to the bed rest study. Although there was an attempt to choose a homogenous group of subjects regarding the training status, this was not fully achieved. That is because not only the absolute fitness level plays a role, but also the activity level in normal daily life. Since subjects were only immobilized for 14 days, the different fitness levels may have had an impact on the velocity and relative degree of weakening in adaptation to disuse. When using longer periods of bed rest, this effect will loose significance since sooner or later atrophic processes will be initiated independently in every subject from the previous fitness level. The examination of balance performance showed similar results. Subjects did not indicate the expected decreases in balance performance as described in chapter 5. Levels of balance performance were different before the study, ranging from high to low balance skills. Decreases in the performance level only became obvious when subjects had to perform very challenging tasks, which may be an indicator for the 7 General Discussion 93 onset of degenerative processes concerning balance performance. For this experiment a longer period of immobilization may have possibly resulted in a different outcome. Moreover, the walk to and back from the training room twice daily may have impacted more than expected, the response of balance performance to bed rest. The fact that 14 days of bed rest under very controlled conditions did not affect muscle and balance performance in general showed the importance of a high level of standardization of study protocols, especially with respect to diet, body position and experiments during the bed rest period that may have an impact on the adaptation of muscle and balance performance. The results showed how much the response depended on the individual subject and muscle that was investigated. The approach to investigate knee cartilage morphology with respect to space flight or immobilization of healthy subjects was fairly new. The results indicated that changes due to bed rest did occur; however further research has to be performed to really understand the findings and their underlying mechanisms. So far, the decrease in cartilage thickness of the weight bearing regions of the tibia fits into the concept of degenerative processes in response to immobilization of the human body. Regarding our second hypothesis, that vibration training has the potential to counteract the effects of 14 days of bed rest, the difficulty was that our first hypothesis generally could not be confirmed. Consequently, vibration training could not act as a countermeasure since the expected degenerative processes did not occur. However, the training protocol and the training intensity were not designed in order to increase muscle or balance performance but to minimize the rate of degeneration. Thus, it did not seem surprising that vibration training did not lead to a change in the response to bed rest, when the specific system did not show degeneration, for example, the MVC for knee extensor muscles. The deterioration of the bed rest effects that could be observed for balance performance as well as for power and MVC of the knee flexors had not been expected before. Again, this may have been due to the length of the investigation and the days of the experiments. Compared to the differences in fitness levels among the subjects, the training protocol that was applied seems to fail individualization. Additionally, the training intensity was not adapted progressively throughout the bed rest period which we would now recommend, based on the results of our investigation. In general, for the testing of training measures in the scope of bed rest studies longer duration of immobilization should be considered. This would favour both the deconditioning as well as the training processes that are both critical for the 7 General Discussion 94 outcome of the study. In the VBR-Study it had been expected, that the 14 days of immobilization would lead to a general deconditioning in all subjects, however this was not the case. The assumption, that a general deconditioning would occur, resulted in the general development of a training protocol that should not overload our subjects, but adequately counteract the bed rest effects. As this deconditioning was missing in some parts, the training intensity was not appropriate to impact the performance levels anymore. The individual tailoring of the training protocol represents another important variable for the outcome. In future studies, a more site specific training should be considered compared to the general whole body vibration training in this study. This would result in the use of regular strength training exercises on a vibration platform that are muscle specific. Based on the results of the VBR-Study and its predetermined conditions, a general recommendation for a vibration training protocol that can counteract bed rest induced changes in muscle and balance performance, as well as cartilage morphology and biology, cannot be given, but potential remains that whole body vibration can positively change the responsiveness to resistance training. However, controlling the training intensity that leads to anabolic responses in the human body is not trivial and needs a high level of individualization. It should be necessary to consider the initial training status during recruiting and screening the subjects. Within this focus, a homogeneous group of subjects should be aspired. Generally, higher training intensities are recommended that are tailored to the individual performance levels as well as the individual responses to the bed rest intervention. Consequently, future studies are needed in order to optimize countermeasures for bed rest induced degradation of tissues of the human organism. 8 Summary 95 8 Summary The Vibration-Bed-Rest-Study (VBR-Study) was performed to investigate the potential of whole body vibration training to counteract degenerative effects of 14 days of 6° head down tilt bed rest (6°-HDT bed rest) on the human body. The effects of immobilization with and without vibration training on different tissues and organs, including skeletal muscle performance, balance performance and articular cartilage, were determined. The following general hypotheses were tested: a) 14 days of 6°-HDT bed rest lead do a general deconditioning of the human body. b) Vibration training has the potential to counteract deconditioning during 14days of 6°-HDT bed rest in terms of slowing down the effects or even preventing them. In this thesis, the results of the following experiments were presented and discussed: o Skeletal Muscle Performance (Chapter 4), o Balance Performance (Chapter 5), o Cartilage biology and morphology (Chapter 6). Eight healthy male subjects (age: 26 ± 5 years; mass: 78 ± 10 kg; height: 179 ± 10 cm) participated in the study after giving their informed consent. The study was performed in a cross-over-design where each subject received vibration training in one phase and a control intervention in the other. During the training intervention, subjects trained 2 x 5 minutes per day at 20 Hz with ~ 3 mm amplitude on a vibration plate (Galileo 900). Subjects walked a defined path to the training room and back twice daily. The schedules during the control and the vibration intervention were identical except for the vibration of the plate. By this study design we were able to interpret the real ‘vibration effect’. The experiments on muscle performance, balance performance and cartilage morphology were scheduled before and after the 14 days of 6°-HDT bed rest. Blood sampling for the analysis of biomarkers was done regularly at predefined times during the whole study. Muscle performance was measured in maximum voluntary contraction (MVC) and maximal power. MVC did not change due to bed rest for the knee flexor and knee extensor muscles. When subjects received vibration training there was a significant decrease in MVC for the knee flexor muscles, but not for the knee extensor muscles. Maximal power did not change due to bed rest for the knee flexor muscles. However, there was a significant decrease in maximal power of the knee flexors when subjects received vibration training. In the knee extensors, bed rest lead to a 8 Summary 96 significant decrease in maximal power which could be prevented by vibration training. The results indicated that changes in MVC and power after 14 days of 6°HDT bed rest under the given conditions were muscle and subject specific and may have depended on their initial physical status. In reference to the power of the knee extensors, the used training protocol was sufficient to cause a significant difference in bed rest effects with and without training. Thus, vibration training with the protocol used had the potential to affect the response of muscle to bed rest induced immobilization. Balance performance was measured with the Posturomed® device, using the parameters ‘holding time’ and ‘displacement’. Bed rest did not lead to a general deterioration in both parameters. Vibration training lead to a significant decrease in holding time and an increased in displacement of the Posturomed®, which reflected a decline in the performance level. The results may have been impacted by the early point in time of the measurement, which did not allow for adaptation to the training process, in addition to the relatively short duration of the bed rest and the training period. Also, vibration training is a very complex and demanding input for our postural receptor system and the central nervous system, which may possibly have caused an acute disorientation that lead to the results. Articular cartilage thickness was measured using magnet resonance imaging (MRI) of the right knee. Additionally, serum concentrations of ‘Cartilage oligometric matrix protein’ (COMP) were analysed from 10 blood samples taken throughout the study. Decreases in average and maximum cartilage thickness after bed rest were observed for the tibial condyle and the effects inverted into an increase when subjects received vibration training. No changes were obtained for the femoral condyle. After 24h of 6°-HDT bed rest, serum COMP concentration decreased significantly and the values returned to baseline after bed rest. Vibration training did not alter the response of serum COMP concentrations. This study showed that decreases in cartilage thickness after a 14-day bed rest can be observed and that vibration training may be able to counteract this effect. Changes in cartilage thickness could reflect a change in mechanical properties of articular cartilage due to the bed rest and the control intervention. Bed rest resulted in a reduction of serum COMP concentrations within less than two days which might have been caused by decreased diffusion of COMP molecules from the cartilage into serum due and / or might reflect a change in cartilage metabolism in response to a lack of exposure of the joint to mechanical loading. Summarizing the results, our general hypotheses were not completely substantiated. It can be stated that the degenerative effects of immobilization did not 8 Summary 97 reach the degree that was previously expected. Amongst others, the effect of the very controlled study conditions, the normo-caloric diet and the allowance to stand up and walk to the training room and back twice a day might have contributed to this outcome. Also, the pre-study training status may impact the bed rest effects more than expected. The training intensity was chosen in order to prevent or decelerate the de-conditioning of the human body due to bed rest. As this deconditioning was missing in some parts, the training intensity was not appropriate to impact the bed rest effects anymore. The observed decline in performance due to the vibration training has not been expected before. Based on the findings of the VBR-Study, we cannot recommend generally pure vibration training as a countermeasure for changes in muscle performance, balance performance and articular cartilage morphology. For the latter, our results showed that cartilage in the knee joint is responsive to both unloading and vibration training. However, further research is encouraged in order to specify the responses. It is likely that the combination of whole body vibration with resistance training will lead to more promising results. Additionally, we suggest considering the initial training status when recruiting and screening subjects. With this in focus, a homogeneous group of subjects should be aspired. Generally, higher training intensities are recommended, in addition to an individually tailored vibration training protocol for each subject with a progressively increasing training intensity. 9 Zusammenfassung 98 9 Zusammenfassung Im Rahmen der ‚Vibration-Bed-Rest-Study’ (VBR-Studie) wurde der Einsatz von Vibrationstraining als Gegenmaßnahme für die degenerativen Auswirkungen von Bettruhe in 6°-Kopftieflage (6°-head-down-tilt (6°-HDT)) untersucht. Dazu wurden 8 Probanden für 14 Tage in Bettruhe mit 6°-HDT immobilisiert. Die Auswirkungen von Bettruhe mit und ohne Einsatz von Vibrationstraining auf unterschiedliche Gewebe und Organe wurden untersucht, darunter z.B. die muskuläre Leistungsfähigkeit, die Gleichgewichtsfähigkeit, sowie Gelenkknorpel im Knie. Gegenstand der Untersuchung waren die folgenden allgemeinen Hypothesen: a) 14 Tage HDT-Bettruhe führen zu einer allgemeinen Dekonditionierung des menschlichen Körpers. b) Die Anwendung von Vibrationstraining während 14-tägiger Bettruhe in 6°-HDT kann dieser Dekonditionierung entgegenwirken. Das zeigt sich in einer Verlangsamung oder Aufhebung der zuvor beobachteten Effekte. In dieser Dissertation werden die Ergebnisse der folgenden Untersuchungen präsentiert und diskutiert: - Muskuläre Leistungsfähigkeit der unteren Extremität (Kapitel 4) - Gleichgewichtsfähigkeit (Kapitel 5) - Gelenkknorpelbiologie und –morphologie (Kapitel 6) Acht gesunde männliche Probanden (Alter: 26 ± 5 Jahre; Gewicht: 78 ± 10 kg; Größe: 179 ± 10 cm) nahmen an der VBR-Studie teil, die im ‚Crossover-Design’ mit zwei Studienphasen durchgeführt wurde. Jeder Proband erhielt in einer Phase Vibrationstraining und in der zweiten Phase eine Kontrollintervention. Während der Trainingsintervention in der Bettruhephase trainierten die Probanden 2 mal täglich für 5 mal 60 Sekunden auf der Vibrationsplatte (Galileo900) bei ein Frequenz von 20 Hz und einer Amplitude von ~ 3 mm. Die Strecke zum und vom Trainingsraum wurde zweimal täglich gegangen. Die Abläufe waren identisch für die Kontroll- und die Trainingsintervention, lediglich die Vibrationsplatte wurde während der Kontrollintervention nicht angestellt. Dieses Studiendesign ermöglichte es daher, den isolierten „Vibrations-Effekt“ zu untersuchen. Die Experimente zur muskulären Leistungsfähigkeit, Gleichgewichtsfähigkeit und Kniegelenksknorpel wurden jeweils vor und nach der Bettruheintervention durchgeführt. Blutabnahmen für Biomarker fanden in regelmäßigen Abständen während der gesamten Untersuchung statt. Die Kraftleistungsdiagnostik zeigte keine Veränderungen in der Maximalkraft der Kniebeuger und Kniestrecker durch Bettruhe. Vibrationstraining führte zu einer 9 Zusammenfassung 99 Verschlechterung der Maximalkraft in den Kniebeugern, nicht aber in den Kniestreckern. Die maximale Leistung zeigte in den Kniebeugern keine Veränderung durch Bettruhe, Vibrationstraining veränderte das Ergebnis nicht. In den Kniestreckern nahm die maximale Leistung nach Bettruhe signifikant ab, was durch Vibrationstraining aufgehalten werden konnte. Die Ergebnisse zeigten, dass eine Veränderung der Maximalkraft sowie der maximalen Leistung nach einer 14tägigen Bettruhe unter den gegebenen kontrollierten Bedingungen sehr muskel- und probandenspezifisch auftritt, was an der initialen Leistungsfähigkeit liegen kann. Betrachtet man die maximale Leistung, so konnte Vibrationstraining den Bettruheeffekt für die Kniestrecker signifikant beeinflussen. Die Gleichgewichtsfähigkeit wurde mit Hilfe des Posturomed® untersucht, die Messgrößen waren die Haltezeit und die Auslenkung des Posturomed® bei der Ausübung vorgegebener Übungen. Bettruhe führte zu keiner generellen Veränderung in beiden Parametern. Wurde Vibrationstraining angewendet, so verschlechterten sich Haltezeit und Auslenkung signifikant. Beide Ergebnisse stützen die Ausgangshypothese nicht, dass Bettruhe zu einer Abnahme der Gleichgewichtsfähigkeit führt. Im Gegenteil, Vibrationstraining verschlechterte den Bettruhe-Effekt. Als Grund kann der frühe Messzeitpunkt genannt werden, der keine adäquate Zeit zu einer Trainingsanpassung zuließ, zusätzlich zu der relativ kurzen Bettruhe- und Trainingsintervention. Außerdem stellt Vibrationstraining einen sehr komplexen und anspruchsvollen Reiz für die Propriozeptoren und das zentrale Nervensystem dar, was zu einer akuten Irritation führen kann. Knorpeldicke wurde mit Hilfe der bildgebenden Magnet Resonanz (Magnet Resonance Imaging (MRI)) gemessen. Zusätzlich wurden die Serum- Konzentrationen von ‚Cartilage Oligometric Matrix Protein’ (COMP) untersucht. Eine Abnahme der mittleren sowie der maximalen Knorpeldicke nach 14.Tagen Bettruhe konnte an den Tibia-Kondylen festgestellt werden, nicht aber für den Femur. Vibrationstraining führte zu einer Zunahme der mittleren und maximalen Knorpeldicken. Serum-COMP-Konzentrationen nahmen nach 24 Stunden in Bettruhe signifikant ab und stiegen direkt nach der Bettruhe wieder auf das Ausgangsniveau an. Vibrationstraining veränderte diese Reaktion nicht. Die Ergebnisse der Knorpeluntersuchungen zeigten eine Abnahme der Knorpeldicke in der Tibia und eine Umkehr des Effektes durch Vibrationstraining, was auf eine Veränderung in den mechanischen Eigenschaften von Knorpel durch die Kontroll- sowie die Trainingsintervention zurückzuführen sein könnte. Die Veränderungen der Serum-COMP-Konzentration ist möglicherweise auf veränderte Transportbedingungen der Fragmente aus dem Gelenk zurückzuführen und könnte 9 Zusammenfassung 100 auf eine Veränderung im Knorpelstoffwechsel durch die mangelnde mechanische Belastung in Bettruhe hinweisen. Zusammenfassend konnten die allgemeinen Hypothesen der Untersuchung nicht vollständig bestätigt werden. Degenerative Veränderungen durch 14 Tage in HDTBettruhe konnten für muskuläre Leistungsfähigkeit, Gleichgewichtsfähigkeit und Kniegelenksknorpel mit den hier angewendeten Methoden nicht in dem erwarteten Ausmaß festgestellt werden, beziehungsweise waren parameter- und probandenspezifisch sehr unterschiedlich. Die Gründe dafür können vielfältig sein, beigetragen dazu haben sicher die sehr kontrollierten Bedingungen, der ausgeglichene Energiehaushalt, das Aufstehen, um zum Trainingsraum zu laufen, sowie der initiale Trainingszustand der Probanden. Das Vibrationstraining wurde in seiner Intensität so gewählt, dass es Organe und Gewebe vor Degeneration bewahren oder den Prozess verlangsamen sollte. Die zum Teil ausbleibende Degeneration führte dazu, dass der Trainingsreiz unter Umständen nicht mehr angemessen war. Wenn Bettruhe keinen negativen Effekt auf das jeweilige System hatte, so konnte Vibrationstraining dann auch nicht mehr als Gegenmaßnahme wirken. Die zum Teil gefundenen negativen Effekte waren so nicht erwartet worden. Auf Grundlage der hier vorgestellten Ergebnisse kann isoliertes Vibrationstraining nicht generell als Gegenmaßnahme für Effekte von Bettruhe in 6°-HDT auf muskuläre Leistungsfähigkeit, Gleichgewichtsfähigkeit und Gelenkknorpel empfohlen werden. Dennoch sollten weitere Untersuchungen folgen, um die Kombination von Vibrationstraining mit herkömmlichen Krafttrainingsmethoden im Rahmen von Bettruhestudien zu untersuchen, und um die Ergebnisse für Gelenkknorpel zu spezifizieren. 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International Journal of Sports Medicine 18, S308-S309. 11 APPENDIX – Publications related to the VBR-Study 112 11 APPENDIX – Publications related to the VBR-Study a) Congress Abstracts Liphardt AM, Jansen C, Kleinöder H, Heer M, Mester J (2007): The potential of whole body vibration training during 14-days of 6°-head down tilt bed rest to affect balance. 4th European Congress: Medicine in Space and extreme Environments, Berlin, Germany Zange J, Liphardt AM, Schmidt A, Müller K, Kleinöder H, Heer M, Mester J (2006): 20-Hz whole body vibration training fails to counteract the decrease in leg muscle performance and volume induced by 14 days of 6° head down tilt bed rest. 8th Congress of Medicine and Mobility, Berlin, Germany. Baecker N, Liphardt AM, Frings P, Heer M (2006): Effects of vibration training on bone metabolism in immobilized healthy subjects. 8th Congress of Medicine and Mobility, Berlin, Germany. Liphardt AM, Bäcker N, Mündermann A, Koo S, Andriacchi T, Zange J, Mester J, Heer M (2006): The potential of vibration training to affect the response of muscle, bone and cartilage during short term bed rest. 15th World Congress of Biomechanics, Munich, Germany. Liphardt AM, Mündermann A, Koo S, Bäcker N, Andriacchi T, Zange J, Mester J, Heer M (2006): Changes in Cartilage Morphology of the Knee after 14-days of Bed Rest. 36th COSPAR Scientific Assembly, Beijing, China. Liphardt AM, Adams F, Gottschalk S, Bäcker N, Frings P, Heer M, Luft FC2, Jordan J, Boschmann M (2006): Impact of daily whole body vibration training (WVT) on muscle blood flow and metabolism during 14 days of bed rest. 11th Annual Congress of the European College of Sport Science, Lausanne, Switzerland. Liphardt AM, Zange J, Schmidt A, Kleinöder H, Heer M, Mester J (2006): 20-Hz Whole body vibration training fails to counteract negative effects of 14 days of bed rest on muscle performance. 11th Annual Congress of the European College of Sport Science, Lausanne, Switzerland. 11 APPENDIX – Publications related to the VBR-Study 113 Zange J, Liphardt AM, Müller K, Mester J (2006): 20Hz whole body vibration training fails to counteract the decrease in leg muscle volume induced by 14 days of 6° head down tilt bed rest. 11th Annual Congress of the European College of Sport Science, Lausanne, Switzerland. Liphardt AM, Mündermann A, Bäcker N, Zange J, Mester J, Heer M (2006): Serum COMP concentration is sensitive to a 14.day bedr rest intervention. 52nd Annual Meeting of the Orthopaedic Research Society, Chicago, Illinois, USA. Bäcker N, Liphardt AM, Frings P, Boese A, Heer M (2005): Effects of mechanical stimuli via vibration plate training on bone metabolism in immobilized healthy subjects. 56th International Astronautical Congress, Fukuoka, Japan. Liphardt AM, Mündermann A, Koo S, Zange J, Mester J, Heer M (2005): The Effect of Vibration Training During 14-Day Bed-Rest on Articular Cartilage Morphology. European Space Agency (ESA) and International Society of Gravitational Physiology (ISGP) Joint Life Science Conference, Cologne, Germany. Zervoulakos P, Blank C, May F, Gauger P, Liphardt AM, Heer M, Beck L (2005): Vibration training fails to improve orthostatic tolerance after 14 days of 6° HDT bed rest. European Space Agency (ESA) and International Society of Gravitational Physiology (ISGP) Joint Life Science Conference, Cologne, Germany. 12 Danksagung 114 12 Danksagung Ich bedanke mich herzlich bei allen Personen, die mich bei der Erstellung dieser Arbeit unterstützt und begleitet haben. Mein besonderer Dank gilt: Prof. Dr. Dr. h.c. mult. Joachim Mester für die Überlassung des Themas sowie die fachliche Diskussion und die ständige Bereitschaft mich zu unterstützen. Frau PD. Dr. Martina Heer für die Möglichkeit diese Studie in ihrer Abteilung (Weltraumphysiologie, DLR-Institut für Luft- und Raumfahrtmedizin) durchführen zu dürfen. Auch für die zahlreichen, intensiven wissenschaftlichen Diskussionen, in denen ich unendlich gelernt habe und die mich in meinem Tun immer bestärkt haben, danke ich ihr von Herzen. Sie hat mich zu jeder Zeit voll unterstützt und es mir ermöglicht die Ergebnisse meiner Arbeit auch auf nationalen und internationalen wissenschaftlichen Kongressen zu präsentieren. Herzlichen Dank dafür! Frau Dr. Natalie Bäcker für die hervorragende Betreuung, die vielen Gespräche, sowie für die organisatorische und wissenschaftliche Unterstützung bei der Durchführung der VBR-Studie. Ihre Erfahrungen und Kenntnisse waren eine sehr wertvolle Hilfe und unerlässlich für den erfolgreichen Abschluss meiner Dissertation. PD Dr. Jochen Zange für seine Unterstützung und die wissenschaftliche Diskussion bei der Fertigstellung der Arbeit. Frau Dr. Petra Frings-Meuthen für die vielen Diskussionen und hilfreichen Kommentare. Meinen Probanden für ihre Kooperationsbereitschaft und ihr großes Engagement bei allen Experimenten. Prof. Dr. James Wakeling, Simon Fraser University, Vancouver, Kanada, und Dr. Annegret Mündermann, University of Otago, Dunedin, Neuseeland, für das Lesen des Manuskripts, die wissenschaftlichen Diskussionen und die unermüdliche Unterstützung. Prof. Dr. Thomas P. Andriacchi, Stanford University, Stanford, USA, für die freundliche Aufnahme als Gaststudent in seinem Team und die Unterstützung bei der Auswertung der Knorpeldaten. Dr. Seungbum Koo, Stanford University, Stanford, USA, für die wissenschaftliche Diskussion und Hilfe bei der Auswertung und Interpretation der Knorpeldaten. Dr. Michael Boschmann, Charité Berlin, für das Lesen der Arbeit und seine Bereitschaft als Mitglied der Prüfungskommission zu Verfügung zu stehen. Frau Dr. Francisca May und Herrn Christoph Blank für ihren unermüdliche Einsatz bei der medizinischen Betreuung unserer Probanden. 12 Danksagung 115 Frau Gabriele Kraus und Frau Jette Hjorth-Müller für ihre Hilfe bei der analytischen Auswertung im Labor. Herrn Henning Soll und Frau Heidi Bonnist für die sehr erfolgreiche Zusammenarbeit bei der psychologischen Auswahl der Probanden, sowie Herrn Paul Kuklinski und Herrn Götz Kluge und Team für die Unterstützung bei der medizinischen Auswahl der Probanden. Den Mitarbeiterinnen und Mitarbeitern des Instituts für Trainingswissenschaft und Sportinformatik, DSHS Köln, für ihre Unterstützung bei der Planung und Durchführung der Kraftleistungsdiagnostik, insbesondere den beiden ehemaligen Diplomanden Christiane Jansen und Axel Schmidt. Den Mitarbeitern der Abteilung Weltraumphysiologie, DLR-Institut für Luft- und Raumfahrtmedizin, für ihren unermüdlichen Arbeitseinsatz sowie die freundschaftliche Zusammenarbeit und Arbeitsatmosphäre. Der Zusammenhalt und die ständige Unterstützungsbereitschaft auch in arbeitsintensiven Zeiten haben mich sehr beeindruckt. Ohne ihren Einsatz wäre die Durchführung der VBR-Studie nicht möglich gewesen. Herrn Roy McLean für das Lesen und Korrigieren des Manuskripts als Muttersprachler. Dem DLR sowie dem Deutschen Akademischen Austauschdienst und der ‚International Society of Biomechanics’ für die finanzielle Unterstützung. Meinen Eltern für ihre Liebe und die immerwährende Unterstützung und Bestärkung in meinem Tun. Meinem Mann Jan und unserer Tochter Mia-Elisa für ihre Liebe, Geduld und Unterstützung. 13 Curriculum Vitae 116 13 Curriculum Vitae Name: Anna-Maria Liphardt, Dipl. Sport Scientist Date of birth: 02.02.1978 Place of birth: Eschwege, Hessen, Germany Parents: Dieter Liphardt g Edith Liphardt geb. Escher Family status: married, one child EDUCATION 2003 / Jun – present PhD student German Sport University Cologne, Köln, Germany 1998 /Oct 2003 / May Sport Science (Diploma) German Sport University Cologne, Köln, Germany Thesis Title: Soft Tissue Vibrations of the Lower Extremity during Walking 1998 / Oct 2003 / Dec Biological Education (Staatsexamen) Universität Köln, Cologne, Germany 1997 / Jun Allgemeine Hochschulreife (Abitur) Herderschule Kassel, Germany PROFESSIONAL EXPERIENCE 2007 / May - present Research Assistant, Institute of Training Science and Sport Informatics, German Sports University Cologne (DSHS), Köln, Germany (part time) 2007 / June - present Research Assistant, Institute of Aerospace Medicine German Aerospace Center, Köln, Germany (part time) 2007/ April - present Assistant lecturer Seminar: Modern insight of training with children and adolescents. German Sport University (DSHS) Cologne, Cologne, Germany 2006 / Aug - 2007 / April Maternity leave 2003 / Jun – 2006 / Aug Ph.D. Candidate, Institute of Aerospace Medicine German Aerospace Center, Cologne, Germany Project: ‘Vibration as a countermeasure for the physiological effects of space flight’ Supervisor: PD Dr. Martina Heer, Prof. Dr. Joachim Mester 13 Curriculum Vitae 117 2005 / May Visiting Student, Biomotion Laboratory Stanford University, Palo Alto, USA Project: ‘The effect of vibration training during immobilization on knee cartilage’ Supervisor: Dr. Anne Mündermann, Dr. Tom Andriacci 2004 / Oct – 2004 / Nov Visiting Student, Biomotion Laboratory Stanford University, Palo Alto, USA Project: ‘The effect of vibration training during immobilization on knee cartilage’ Supervisor: Dr. Anne Mündermann, Prof. Dr. Tom Andriacci 2002 / Aug – 2003 / Jan Visiting Student, Human Performance Laboratoy University of Calgary, Canada Project: ‘Soft Tissue Vibrations of the Lower Extremity During Walking’ Supervisor: Dr. James Wakeling, Prof. Dr. Benno Nigg 2000 – 2003 Student Research Assistant, Department of Individual Sports German Sport University Cologne, Germany Specialization: Gymnastics AWARDS AND SCHOLARSHIPS 2006 Young Investigator Award of the German Sports University Cologne, Germany 2005 Young Investigator Award at the European Space Agency (ESA) and International Society of Gravitational Physiology (ISGP) ‘Joint Life Science Conference’, 2nd Place 2005 European Space Agency, Young Investigator Travel Sponsorship 2005 ISB Travel Grant, International Society of Biomechanics 2004 Travel Grant, Deutscher Akademische Austausch Dienst (DAAD), Germany 2003 Young Investigator Award of the European College of Sport Science, Finalist 2002 “Study Abroad Award”, full competitive scholarship, Deutscher Akademischer Austausch Dients (DAAD), Germany PUBLICATIONS JOURNALS Wakeling JM, Liphardt AM (2005). Task specific recruitment of motor units for vibration damping. Journal of Biomechanics, J Biomech. 2006;39(7):1342-6. Wakeling JM, Liphardt AM, Nigg BM (2003). Muscle activity reduces soft-tissue resonance at heel-strike during walking. Journal of Biomechanics 36, 1761 – 1769 13 Curriculum Vitae 118 PEER-REVIEWED ABSTRACTS Liphardt AM, Jansen C, Kleinöder H, Heer M, Mester J (2007): The potential of whole body vibration training during 14-days of 6°-head down tilt bed rest to affect balance. 4th European Congress: Medicine in Space and extreme Environments, Berlin, Germany Zange J, Liphardt AM, Schmidt A, Müller K, Kleinöder H, Heer M, Mester J (2006): 20-Hz whole body vibration training fails to counteract the decrease in leg muscle performance and volume induced by 14 days of 6° head down tilt bed rest. 8th Congress of Medicine and Mobility, Berlin, Germany. Bargmann A, Liphardt AM, Rosenberger A, Zange J, Beck L (2006): Effects of vibration training on the cardiovascular system (Pilot-Vibration-Training Study). 8th Congress of Medicine and Mobility, Berlin, Germany. Baecker N, Liphardt AM, Frings P, Heer M (2006): Effects of vibration training on bone metabolism in immobilized healthy subjects. 8th Congress of Medicine and Mobility, Berlin, Germany. Rosenberger A, Liphardt AM, Bargmann A, Müller K, Zange J, Mester J (2006): Effects of vibration training and resistive exercise on fatigability of leg muscles (Pilot-Vibration-Study). 8th Congress of Medicine and Mobility, Berlin, Germany. Liphardt AM, Bäcker N, Mündermann A, Koo S, Andriacchi T, Zange J, Mester J, Heer M (2006): The potential of vibration training to affect the response of muscle, bone and cartilage during short term bed rest. 15th World Congress of Biomechanics, Munich, Germany. Liphardt AM, Mündermann A, Koo S, Bäcker N, Andriacchi T, Zange J, Mester J, Heer M (2006): Changes in Cartilage Morphology of the Knee after 14-days of Bed Rest. 36th COSPAR Scientific Assembly, Beijing, China. Liphardt AM, Adams F, Gottschalk S, Bäcker N, Frings P, Heer M, Luft FC2, Jordan J, Boschmann M (2006): Impact of daily whole body vibration training (WVT) on muscle blood flow and metabolism during 14 days of bed rest. 11th Annual Congress of the European College of Sport Science, Lausanne, Switzerland. Liphardt AM, Zange J, Schmidt A, Kleinöder H, Heer M, Mester J (2006): 20-Hz Whole body vibration training fails to counteract negative effects of 14 days of bed rest on muscle performance. 11th Annual Congress of the European College of Sport Science, Lausanne, Switzerland. Zange J, Liphardt AM, Müller K, Mester J (2006): 20Hz whole body vibration training fails to counteract the decrease in leg muscle volume induced by 14 days of 6° head down tilt bed 13 Curriculum Vitae 119 rest. 11th Annual Congress of the European College of Sport Science, Lausanne, Switzerland. Liphardt AM, Mündermann A, Bäcker N, Zange J, Mester J, Heer M (2006): Serum COMP concentration is sensitive to a 14.day bedr rest intervention. 52nd Annual Meeting of the Orthopaedic Research Society, Chicago, Illinois, USA. Bäcker N, Liphardt AM, Frings P, Boese A, Heer M (2005): Effects of mechanical stimuli via vibration plate training on bone metabolism in immobilized healthy subjects. 56th International Astronautical Congress, Fukuoka, Japan. Liphardt AM, Mündermann A, Koo S, Zange J, Mester J, Heer M (2005): The Effect of Vibration Training During 14-Day Bed-Rest on Articular Cartilage Morphology. European Space Agency (ESA) and International Society of Gravitational Physiology (ISGP) Joint Life Science Conference, Cologne, Germany. Zervoulakos P, Blank C, May F, Gauger P, Liphardt AM, Heer M, Beck L (2005): Vibration training fails to improve orthostatic tolerance after 14 days of 6° HDT bed rest. European Space Agency (ESA) and International Society of Gravitational Physiology (ISGP) Joint Life Science Conference, Cologne, Germany. Liphardt AM, Wakeling JM, Nigg BM, Mester J (2004): Potential of vibration training for the maintenance of muscle performance during spaceflight. 25th Annual International Gravitational Physiology Meeting, Russian Academy of Sciences, Moscow, Russia. Liphardt AM, Wakeling JM (2004): Functional recruitment of muscle during vibration damping. 9th Annual Congress of the European College of Sport Science, ClairmontFerrand, France. Liphardt AM (2003): Vibration Training as a countermeasure against the effects of microgravity on bone and skeletal muscle. 1st Space Medicine Workshop for Students, European Astronaut Centre, Cologne, Germany. Liphardt AM, Wakeling JM, Nigg BM, Mester J. (2003). Effect of different shoe hardnesses on EMG intensity and soft tissue vibrations of the lower extremity during walking. 8th Annual Congress of the European College of Sport Science, Salzburg, Austria. Köln, den 30.01.2008 ___________________________________________________________________ Dipl.-Sportwiss. Anna-Maria Liphardt