Regular exercise is well-known to increase both muscle mass and muscle strength (Greenleaf et al., 1989; Casaburi, 1992; Jones & Round, 1992). Therefore, it has been used as a countermeasure in spaceflight programs as soon as the muscle degrading effects of a stay in microgravity were noticed (Stein & Gaprindashvili, 1994). If muscle strength is increased, the performance of "balance keeping tasks" might also improve.

Until now, no comparisons have been made between spaceflights with and without exercise. Consequently, the scientifical basis of the effectiveness of in-flight exercise protocols to increase muscle mass and muscle strength is rather weak (Tipton et al., 1996). Because bed rest studies have shown that the losses in muscle mass and muscle strength are larger without the performance of exercise (Grigoriev et al., 1992; Bloomfield, 1997), and because exercise has extensively been shown to increase the size and strength of muscle tissue in any population (ACSM, 1990), the muscle sparing effects of exercise during spaceflight is commonly assumed to be self-evident.

Although the muscle tissue enhancing effects of exercise are likely, exercise is often not able to nullify the in-flight losses in muscle tissue. Therefore, additional countermeasures have been used. Hormone therapy, pharmacological intervention using catecholamine derivatives, and electrostimulation have been found to augment the effects of exercise, but cannot replace it (Rabin et al., 1993; Baldwin, 1996). Percutaneous electrostimulation, which is used by Russian cosmonauts on long-duration flights (Grigoriev et al., 1991b; Convertino, 1996), has some potential advantages. In hindlimb suspension of rats, electrostimulation is able to reverse certain muscle parameters, such as the isoform expression, but fails to maintain either muscle mass or strength at it’s pre-intervention values (Leterme & Falempin, 1994).

After short term spaceflight, the recovery of muscular changes after return to earth is very quick. In rats, strength losses after thirteen days of spaceflight are drastically modified within two days (Oganov et al., 1991a). Longer duration stays also require longer recovery periods. A stay of 150 days in the Salyut VII space station by two cosmonauts caused "moderate" losses in the calf muscles, which returned to their pre-flight values 30 days after their return (Stein & Gaprindashvili, 1994). After bed rest, muscle mass and strength can return to their pre-intervention values within several weeks with appropriate resistance training (Bloomfield, 1997). In general, the rate of muscle recovery is more rapid than the rate of loss (LeBlanc et al., 1992).

Although muscle tissue has the ability to return to it’s pre-flight volume and strength characteristics, in-flight exercise is still very important. During long-term missions, in-flight work performance might be detrimented when the degradation of muscle tissue is not counteracted. The health, and even the life, of spacetravellers can be endangered when no countermeasures are taken (Bachl et al., 1993). In addition, when in-flight exercise is not sufficiently performed, the danger of not having the appropriate physique during any re-entry or landing contingencies exists (Convertino, 1990).

3.1 - The mechanisms behind spaceflight-induced changes in muscle tissue

Under weightlessness, muscle atrophy is occurring in every muscle fiber, thereby decreasing the cross-sectional area of the whole muscle (Tesch et al., 1990; Edgerton et al., 1995). It appears that the initial size of muscle fibers influences the degree of atrophy. Data from rats flown in space suggest that larger fibers tend to loose more protein, which is an indication of muscle atrophy (Dudley et al., 1992). These findings have been confirmed in humans (Edgerton et al., 1995).

The changes that occur on the cellular level of the muscle are less well-known. Human muscle biopsies of spacetravellers have not become available until 1995 (Edgerton et al., 1995; Zhou et al., 1995). Despite a five to ten per cent variability between biopsies taken from the same muscle (Zhou et al., 1995), this technique is considered to be a satisfyably precise measure of the interior of the muscle. Before these data were available, animal research, mainly in rats, and bed rest simulations had already given an indication of the cellular changes that occur due to (simulated) weightlessness.

Bed rest studies illustrated that disuse leads to structural changes within muscle fibers. These changes include Z-line irregularities (Z-lines are dark structures inside the myofilaments where actin molecules are attached to), myofibrillar protein disorganization, cellular edema, and the occasional presence of mitochondria in the extracellular space, suggesting a disruption of the muscle sarcolemma (the membrane around a muscle fiber). These structural changes are associated with a reduction in the force-velocity relation (Convertino, 1990; Bloomfield, 1997).

On the cellular level, the larger degree of atrophy that is associated with the postural muscles is also visible. These muscles contain mainly slow fibers, and the slow myosin molecule is the major site of protein loss (Roy et al., 1991; Edgerton et al., 1995). Within slow muscle fibers, other changes occur that can partially explain the velocity dependent changes in muscle strength. Faster contractions were associated with lesser decrements, while the largest losses were recorded in isometric strength (paragraph 2.1.3). This may be explained by the finding that slow muscle fibers acquire some properties of fast twitch fibers. The content of slow-oxidative fibers in the adductor longus muscle of the rat decreases, whereas the intermediate fiber content increases (Tischler et al., 1993). This has also been found in human vastus lateralis muscle after eleven days of spaceflight (Edgerton et al., 1995; Zhou et al., 1995). The increased dependence of the muscle on faster fibers after spaceflight is also seen in the shortening of activation and relaxation times for performing isometric contractions (Baldwin, 1996). Due to the shift from slow to fast myosin isoforms, contractions at a higher velocity are more easy to perform.

As yet, the issue as to what extent the muscle atrophy is responsible for the losses in muscle strength is unresolved (Edgerton et al., 1995). The exact underlying mechanism of the loss in muscle strength is still not clear (Rabin et al., 1993). Convertino (1990) proposed three contributing factors: 1) the loss of load-bearing input to muscle proprioception, 2) a possible contribution of impaired neuromotor mechanisms, and 3) muscle atrophy. The first factor is thought to be the primary factor, while the influence of muscle atrophy becomes important after one week of spaceflight. These three factors are thought to influence muscle function in general, i.e. both it’s strength and fatigue properties (Convertino, 1990).

The first factor, regarding the afferent signals of the nervous system, is evidenced by alterations in proprioceptive inputs and spinal reflex mechanisms. Patellar reflex excitability was increased in two cosmonauts after eighteen days of spaceflight. When a standardized load was applied, the electrical activity increased from 65 microvolts pre-flight to 205 microvolts post-flight (Convertino, 1990). Increased excitability has also been found in the Achilles tendon reflex (Kozlovskaya et al., 1990; Rafolt & Gallasch, 1996).

The second factor, which involves the efferent signals of the nervous system, is evidenced by a decrease in muscle tone. This decrease amounted eight per cent in the tibialis anterior muscle and ten per cent in the quadriceps muscle. The ability to recruit motor units may also be affected (Baldwin, 1996). The electrical efficiency has been reported to drop, as indicated by a larger electrical activity per unit of applied force in the triceps surae (Vorobyov et al., 1983; Convertino, 1990). The maximal EMG response is decreased (Kozlovskaya et al., 1990). These changes are also thought to influence the vestibular problems as described in paragraph 2.3.2 (Vorobyov et al., 1983; Kozlovskaya et al., 1990).

The neural changes can be different between muscles. In the previously mentioned two cosmonauts, there was no change in muscle tone and an increased electrical efficiency in the biceps brachii muscles (Convertino, 1990). These differences between alterations in the upper and lower limbs may be explained by the non-postural nature of the arms and the increased use of the arms to maneuver in microgravity. However, muscle strength of the arms is still reported to drop (Greenleaf et al., 1989). Because no neural alterations in the arms have been reported, these decrements in strength are probably due to the final factor involved: muscle atrophy itself. Because of the loss in contractile elements, less power can be generated due to strength decrements and a lower maximum velocity of contraction (Jones & Round, 1992).

A final issue that is related to the decrease in muscle strength, is increased muscle fatigability. Spaceflight-induced muscle fatigue is assessed by a decrement of mean EMG frequency and an increased isometric tremor amplitude (Rafolt & Gallasch, 1996). This increased fatigability is not caused by muscle atrophy itself (Edgerton et al., 1995). It was even hypothesized that fatigability could decrease due to muscle atrophy, since the perfusion distance between capillaries and muscle fibers was expected to diminish with the disappearance of myofibrils. But the number of capillaries has been found to decrease as well during spaceflight, leaving the ratio of number of capillaries to CSA unchanged (Roy et al., 1991).

A possible cause for the increased muscle fatigue is the more readily recruiting of more fibers, while the fatigability of units increases non-linearly with the number of units recruited. Changes in enzyme kinetics may also play a role (Edgerton et al., 1995). Another possible factor in this increased fatigability, is the shift from slow to fast characteristics on the cellular level. It is well-established that faster fibers have a decreased resistance to fatigue (Zhou et al., 1995).

A separate metabolic issue is the shift in muscle energy sources that occurs in space. In the generation of strength, the muscles become less dependent on fat and more dependent on carbohydrates (Grigoriev et al., 1991b; Zhou et al., 1995). The content of stored lipid in the muscle has also been found to increase (Baldwin, 1996). This may be caused by the increase in insulin receptor density that occurs during spaceflight, thereby relatively increasing the insulin binding capacity (Tischler et al., 1993). Since the use of fat as a substrate is favourable in long-duration exercises (Jeukendrup et al., 1994), this shift in energy sources may also be related to the increased fatigability of muscles.

Spaceflight affects every component of the motor system. The neural control, spinal reflexes and the muscle itself are all hampered by the absence of gravity. No intercorrelation has been found between these three components, despite a large variation in the severity of the alterations. Therefore, each component is thought to have a different origin (Kozlovskaya et al., 1990).

The severity of the losses in muscle strength are dependant on food intake, flight duration, individual resistance and the performance of exercise during the flight (Convertino, 1990; Kozlovskaya et al., 1990; Stein & Gaprindashvili, 1994). The most important factor is without any doubt the performance of exercise. Losses in muscle strength are far more dependant on the volume of physical exercises performed in-flight than on flight duration (Kozlovskaya et al., 1990). This influence of physical exercise makes it an appropriate countermeasure against the deconditioning of the muscular system.

The effects of various exercises on muscle mass, strength, and fatigability have been documented extensively (ACSM, 1990; Casaburi, 1992; Jones & Round, 1992). The results of these studies show that, if certain concepts are kept in mind, the performance enhancing potential of training is enormous. However, the underlying mechanism has yet to be resolved. In this paragraph, some ideas with respect to this underlying mechanism will be reported and the basic concepts of exercise training will be addressed.

In this paragraph, the main attention will be on weight training, or resistance training, which is very effective in increasing both muscle mass and muscle strength (Tesch et al., 1990; Swezey, 1996). Endurance training would be favourable to increase muscle endurance. But the increased muscle fatigue during spaceflight has not been reported to restrain spacetravellers in their work performance either in-flight or post-flight. Therefore, in-flight exercise protocols do not necessarily have to focus on counteracting increased muscle fatigue. In-flight training should focus on counteracting muscle atrophy, and the concurrent decreases in muscle strength. These could seriously limit in-flight work performance during future long-term flights, and could cause problems during any re-entry contingencies (Bachl et al., 1993). The main focus of an in-flight exercise protocol should be on weight training or resistance training, which is the most optimal way to increase muscle strength and muscle mass (Tesch et al., 1990; Convertino, 1991; Kirby et al., 1992).

Endurance training is also able to counteract muscle atrophy (Whittle, 1979), but is less suitable to be used for this purpose, since it is far less time efficient than high intensity resistance training (Convertino, 1991; Bachl et al., 1993; Edgerton et al., 1995). However, endurance training should not be totally excluded from a protocol aimed at increasing muscle mass and muscle strength. Training targeting at endurance and maintaining ones posture increases the efficiency of the training protocol (Castellsaguer, 1995).

The two main concepts of exercise training are the overload principle and the concept of specificity (Jones & Round, 1992). The overload principle means that a muscle tends to increase in strength and size as a result of performing work beyond it’s normal capacity. In space physiology, this is the basis of the performance of in-flight exercise. Although the weightless environment does not place any load on the muscles, thereby allowing them to atrophy, the loads created by daily exercises initiate processes that force the muscular system to maintain itself in such a state that these loads can be borne.

To reach these effects, exercise should be performed regularly. In the case of weight training or resistance training, the American College of Sports Medicine prescribes minimally twice a week a minimum of eight to ten different exercises involving the major muscle groups with a minimum of one set of eight to twelve repetitions to near fatigue per muscle group (ASCM, 1990). The minimum stimulus to generate muscle enhancing effects is a force of about 60 per cent of the maximum, but higher forces induce larger effects (Hortobagyi et al., 1997).

A second concept with respect to performing these exercises, is the concept of specificity. In training a certain task, the performance of this particular task will be maintained or enhanced. For example, dynamic exercises have hardly any effects on isometric strength and training of a specific contraction with a joint held at a certain angle has little effects on the performance of the same contraction but with a different joint angle (Jones & Round, 1992).

Summarizing these two concepts, one can say that regular exercise of a sufficient load leads to specific changes that enhances the trained performance of the muscle. Changes that can occur inside the muscle include fiber hypertrophy, a shift in the expression of slow or fast myosin, an increase in mitochondrial size and number, enhanced enzymatic processes and increased capillarization (Roy et al., 1991; Casaburi, 1992).

Despite the well-known muscle enhancing effects of exercise and the wide practical knowledge how to achieve these effects, the theoretical basis of this relationship is lacking. The changes can be under neural or endocrine control, or can be influenced by a local growth factor directly acting on the muscle (Rabin et al., 1993). The concept of specificity indicates that local factors are dominant, and that if a humoral factor is involved, this factor is initiated by mechanical factors. A possible cause is the occurrence of micro damage to the muscle structure as a result of load bearing. If the strict actin/myosin composition is ruptured, this results in two independent myofibrils. Each of these myofibrils can grow back to the size of the initial myofibril (Jones & Round, 1992). Whether this process actually occurs is still unknown. Thus, the only conclusion that can be drawn is that mechanical stress initiates a series of events, which, if these stresses are applied regularly, leads to an increase in muscle strength and muscle mass. Although the cellular and subcellular changes are unknown, the practical factors that play a role are better understood.

The effects of regular weight or resistance training can be divided into three phases. In the first phase, rapid improvements are made as a result of better neuro-motor control. These effects are very task-specific. The second phase is a marked increase in strength without a matching increase in the cross-sectional area. This is based on either a neural mechanism or an improvement in the architecture of the muscle. The third phase is marked by an increase in both size and strength of the exercized muscles. This third phase starts after twelve weeks of training (Jones & Round, 1992).

The first phase is less important for the purpose of exercise training during spaceflight since these effects are very task-specific. But the completion of this phase is necessary in order to reach the results of the second and third phase. As the last phase is not reached until twelve weeks of training have been performed, this might account for the initial heavy losses in muscle mass the first months of spaceflight. The time course of the sequential events of exercise training may be different in a weightless environment, but it is reasonable to presume that the "neural training phase", i.e. the first and maybe the second phase, will last for several weeks under weightlessness. During this time, no muscle tissue sparing effect is effective. This time delay could have a potential serious effect. Pre-flight performance of the same exercises that are planned in-flight could erase this time delay, making the exercise protocol efficient from the first day it is performed. In the literature, no records of the existence of such pre-flight specific training is found.

Over the years, there has been a broad discussion in the literature which type of contractions would be most efficient in enhancing muscle tissue (e.g. Louisy et al., 1995; Swezey, 1996; Greenleaf, 1997). The overall comparable results of exercise protocols including either isometric, isotonic, or isokinetic contractions, or a combination of these three, already suggested that the type of contraction per se is not a determining factor in increasing muscle strength. Rather, the stimulus should be large enough to invoke changes in strength, as suggested by the overload principle. The most important variable to maintain or increase muscle size, and concomitantly muscle strength, is the production of some minimum force for some minimum amount of time (Roy et al., 1991).

Although isometric, isokinetic and isotonic contractions seem to produce similar results, eccentric contractions seem to be different. Recent research strongly indicates that strength training protocols that include eccentric contractions give superior muscle tissue enhancing results above protocols with only isometric and/or concentric contractions (Berg & Tesch, 1994; Hortobagyi et al., 1996). This does not seem to be dependent on the type of contraction per se, but on the high loads that are produced during eccentric contractions. During eccentric contractions the forces that are generated by the muscle are higher than during isometric contractions (Rozendal et al., 1990; Jones & Round, 1992). In addition, during eccentric contractions muscle activity is increased as a result of the superposition of the reflex activity onto the voluntary nerve reaction (Castellsaguer, 1996). According to the overload principle, eccentric contractions naturally have a larger muscle generating effect.

From the area of space-physiology, it was already hinted that eccentric contractions should be included in in-flight exercise protocols. Under terrestrial conditions, eccentric contractions always occur, but in microgravity they are virtually absent, which made eccentric contractions a potentially essential stimulus for the maintenance of muscle tissue (Convertino, 1991; Kirby et al., 1992). In addition, eccentric contractions are performed at a low cost of ATP and oxygen consumption (Tesch et al., 1990; Convertino, 1991), making them very interesting for performance during spaceflight from an operational point of view. In a spacecraft, oxygen must be generated and all food must be launched and carried along during flight, making exercises that are associated with a low cost of oxygen and calories very attractive (Convertino, 1991; Bachl et al., 1993). A third factor why eccentric contractions are favourable, is that they are less training-specific. Eccentric exercises have a greater effect on isometric strength, than isometric exercises have on eccentric strength (Hortobagyi et al., 1997).

Because of it’s well known muscle mass and muscle strength enhancing characteristics, exercise is the principal countermeasure against spaceflight-induced decrements in muscle mass and muscle strength. The best way to induce muscle hypertrophy is heavy resistance training (Tesch et al., 1990), which also induces increases in muscle strength (Swezey, 1996). Exercise protocols that are performed during spaceflight must, besides being effective, be easy to perform and be as least time consuming as possible. This increases the adherence to the in-flight exercise protocols and is favourable from an operational point of view.

The most efficient exercise protocol to increase muscle mass and muscle strength contains regular (probably daily) exercise training that includes concentric and eccentric contractions. Because the highest losses in muscle strength are recorded in isometric strength, this kind of contractions should also be performed (Diffee et al., 1993). All major muscle groups must be included, but the emphasis must be at the postural muscles. To train the muscles of the arms, it could be sufficient to perform exercises every other, or every third, day.