U.S. human spaceflight programs Mercury and Gemini Prior to launch of the first American
astronaut,
suborbital flights of
non-human primates (
chimpanzees) demonstrated that launch and entry, as well as short-duration microgravity exposure, were all survivable events. The initial biomedical problem faced by
Project Mercury (which ran from 1959 – 1963) was establishment of selection criteria for the first group of astronauts. Medical requirements for the Mercury astronauts were formulated by the
NASA Life Sciences Committee, an advisory group of distinguished physicians and life scientists. Final selection criteria included results of medical testing as well as the candidates' technical expertise and experience. Aeromedical personnel and facilities of the
Department of Defense were summoned to provide the
stress and
psychological testing of astronaut candidates. The screening and testing procedures defined for the selection of Mercury astronauts served as the basis for subsequent selection of Gemini and
Apollo astronauts when those programs were initiated. While the
Mercury flights were largely demonstration flights, the longest Mercury mission being only about 34 hours, Project Mercury clearly demonstrated that humans could tolerate the spaceflight environment without major acute physiological effects and some useful biomedical information was obtained, which included the following: • Pilot performance capability as unaltered by spaceflight • All measured physiological functions remained within acceptable normal limits • No signs of abnormal sensory or psychological responses were observed • The
radiation dose received was considered insignificant from a medical perspective • Immediately after landing, an orthostatic rise in
heart rate and drop in systemic blood pressure were noted, which persisted for 7 to 19 hours post landing Because of the short mission durations of Project Mercury, there was little concern about loss of musculoskeletal function; hence no exercise hardware or protocols were developed for use during flight. However, the selection criteria ensured that astronauts were in excellent physical condition before flight. Biomedical information acquired during the Mercury flights provided a positive basis to proceed with the next step, the
Gemini Program, which took place during the 20 months from March 1965 to November 1966. The major stated objective of the Gemini Program was to achieve a high level of operational confidence with human spaceflight. To prepare for a lunar landing mission, three major goals had to be realized. These were: • to accomplish rendezvous and docking of two
space vehicles • to perform
extravehicular activities and to validate human life support systems and astronaut performance capabilities under such conditions • (germane to this topic) to develop a better understanding of how humans tolerate extended periods of weightless flight exposure Thus, Project Gemini provided a much better opportunity to study the effects of the
microgravity of spaceflight on humans. In the 14-day
Gemini 7 flight, salient observations were undertaken to more carefully examine the physiological and psychological responses of astronauts as a result of exposure to spaceflight and the associated microgravity environment. The Gemini Program resulted in about 2000 man-hours of weightless exposure of U.S. astronauts. Additional observations included the presence of postflight
orthostatic intolerance that was still present for up to 50 hours after landing in soe crewmembers, a decrease in red cell mass of 5 – 20% from preflight levels, and radiographic indications of bone demineralization in the
calcaneus. No significant decrements in performance of mission objectives were noted and no specific measurements of muscle strength or endurance were obtained that compared preflight, in-flight and postflight levels.
Apollo The major objective of the
Apollo Program was the landing of astronauts on the
lunar surface and their subsequent safe return to Earth. The Apollo (1968–1973) biomedical results were collected from 11 crewed missions that were completed within the five-year span of the Apollo Program, from pre-lunar flights (missions 7 through 10); the first lunar landing (mission 11), and five subsequent lunar exploratory flights (mission 12 through 17).
Apollo 13 did not complete its intended lunar landing mission because of a pressure vessel explosion in the Service Module. Instead, it returned safely to Earth after attaining a partial lunar orbit. Essential to the successful completion of the Apollo Program was the requirement for some crew members to undertake long and strenuous periods of extravehicular activity (EVA) on the lunar surface. There was concern about the capability of crew members to accomplish the lunar surface excursions planned for some of the
Apollo missions. Although reduced lunar gravity was expected to make some tasks less strenuous, reduced suit mobility coupled with a complex and ambitious timeline led to the prediction that
metabolic activity would exceed resulting levels for extended periods. Since the nature and magnitude of physiological dysfunction resulting from microgravity exposure had not yet been established (and is still not concisely defined), suitable physiological testing was completed within the constraints of the Apollo Program to determine if crewmember physiological responses to exercise were altered as a consequence of spaceflight. Initial planning for the Apollo Program included provisions for in-flight measurements of salient parameters of concern including physiological responses to exercise. However, the fire in the Apollo 204 spacecraft (also known as
Apollo 1), fatal to astronauts Grissom, White, and Chaffee, resulted in
NASA management initiating changes in the program that eliminated such prospects. This, investigators were left with only the possibility to conduct pre-flight and post-flight exercise response studies and to assume that these findings reflected alterations of
cardiopulmonary and skeletal muscle function secondary to microgravity exposure. It was realized early on that within the context and constraints imposed by the realities of the Apollo missions, the inability to control certain experiment variables would present challenges to many biomedical investigations. Firstly, re-adaption to Earth gravity procedures introduced additional challenges to a well-controlled experiment design since Apollo crew members spent variable amounts of time in an uncomfortably warm spacecraft bobbing in the ocean and additionally,
orbital mechanics constraints on re-entry times imposed crew recovery times that prevented the possibility of conducting pre- and post-flight testing within a similar circadian schedule. The effect of these uncontrollable conditions and that of other physical and psychological stresses could not be separated from responses attributable to microgravity exposure alone. Thus, data relating to the physiological responses to exercise stress in Apollo astronauts must be interpreted within this overall context. No standardized in-flight exercise program was planned for any of the Apollo flights; however, an exercise device (Figure 6-1) was provided on some missions. Crewmembers, when situated in the
Command Module (CM), typically used the exerciser several time per day for periods of 15–20 minutes. The pre- and post-flight testing consisted of graded exercise tests conducted on a bicycle
ergometer. Heart rate was used for determining stress levels, and the same heart rate levels were used for pre- and postflight testing. was based on the Exer-Genie developed by Exer-Genie, Inc.,
Fullerton, CA. Within the cylinder, the nylon cords rotate around a shaft, developing controlled resistance. The cords are attached to loop handles. When not in use, the flight device was stored in a cloth bag (
inset). Although the exact duration of each stress level was adjusted slightly (1–2 minutes) for the later Apollo missions to obtain additional measurements, the graded stress protocol included exercise levels of 120, 140 and 160 beats per minute, corresponding to the light, medium, and heavy work respectively for each individual. For the
Apollo 9 and 10 missions, a stress level of 180 beats per minute was added. The entire test protocol was conducted three times within a 30-day period before lift-off. Postflight tests were conducted on recovery (landing) day and once more at 24 to 36 hours after recovery. During each test, workload, heart rate, blood pressure, and respiratory gas exchange (
oxygen consumption,
carbon dioxide production, and minute volume) measurements were made. For
Apollo 15 to 17 missions,
cardiac output measurements were obtained by the single-breath technique. Arteriovenous oxygen differences were calculated from the measured oxygen consumption and
cardiac output data. The data collected were voluminous and are summarized in tabular form by Rummel et al. In brief, reduced work capacity and oxygen consumption of significant degree was noted in 67% (18 of 27) of the Apollo crewmembers tested on recovery. This decrement was transient, and 85% of those tested (23 of 27) returned to preflight baseline levels within 24–36 hours. A significant decrement in cardiac
stroke volume was associated with diminished exercise tolerance. It was not clear whether the exercise decrement had its onset during flight. If it did, the Apollo data did not reveal the precise in-flight time course because of lack of in-flight measurement capabilities. The astronauts' performance on the lunar surface provided no reason to believe that any serious exercise tolerance decrement occurred during flight, except that related to lack of regular exercise and muscle disuse atrophy. In addition to measurements relating directly to skeletal muscle strength and mass, indirect measurements were made that demonstrated that all Skylab crewmembers had a negative nitrogen balance indicative of skeletal muscle attrition. This was also observed 10 years later in short-duration
Space Shuttle crewmembers. (MRI)", was to non-invasively quantify changes in size, water, and lipid composition in antigravity (leg) muscles after spaceflight. This experiment was the first attempt to measure limb volumes before and after flight since the less sophisticated methods of measuring limb girths during Apollo and SKylab programs were used. The subjects included a total of eight Space Shuttle crewmembers, five from a 7-day flight and three from a 9-day flight. All subjects completed one preflight and two postflight tests on either L-30 or L-16 and on R+2 and R+7. Testing involved obtaining an MRI scan of the leg (soleus and gastrocnemius) at The University of Texas – Houston Health Science Center, Hermann Hospital. Multi-slice axial images of the leg were obtained to identify and locate various muscle groups. Changes in water and lipid content were measured, in addition to CSA, to distinguish changes in fluid versus tissue volumes. Multiple slices were measured by computerized planimetry. CSA and volume of the total leg compartment, soleus, and gastrocnemius were evaluated to assess the degree of skeletal muscle atrophy. The volumes of all 3 compartments were significantly smaller (
p < 0.05) after both the 7 and 9 day Shuttle flights than they were before flight. Volume decreased by 5.8% in the soleus, 4.0% in the gastrocnemius, and 4.3% in the total compartment. These losses were stated to represent the true level of skeletal muscle tissue atrophy and not changes associated with fluid shifts. A comparison between volume losses in the selected muscle groups in short-duration spaceflight on the Space Shuttle, long-duration (119 d)
bed rest, and a (115 d) Shuttle-Mir mission demonstrates the relative time course of the losses (figure 6-9). There is good correlation between long-duration bed rest and spaceflight of similar duration except that losses in the back muscles are much less with bed rest. This likely reflects use of these muscles during bed rest to adjust body position and to reduce the potential for vascular compression and tissue injury. During spaceflight the back muscles are apparently less used because they do not have to support the upright body against Earth gravity and are not used with great force to make positional adjustments of the body as they are during the recumbency of bed rest.
International Space Station (ISS) The International Space Station's (ISS) first crew (Expedition 1) arrived in October 2000; since then there have been 15 additional Increments. The data presented here were collected during the first 11 of the ISS Expeditions. The complexities and shortcomings of collecting scientific data from a laboratory orbiting more than 300 miles above the Earth and completing 18 orbits per day at a speed of more than 17,000 mph with discontinuous voice and data communications, combined with the constraints and limitations of up mass, crew time, and on-board logistics, cannot be overstated. Another problem was exercise hardware that was built and launched but failed to meet science requirements. (The Resistive Exercise Device [RED] science requirement was to provide a load of up to an equivalent of 600 lbs., but the Interim Resistive Exercise Device (iRED) provides only half of that amount. Ground-based studies have shown that it does produce a positive training effect similar to equivalent free weights when used in a high-intensity program, but it will likely not provide sufficient load in a zero-gravity environment to prevent loss of muscle and bone tissue, as determined from parabolic flight studies.) Other problems were failure at one time or another of each piece of onboard exercise hardware with reduced utilization at other times, and other limitations imposed because transmission of forces to the space frame have confounded inflight exercise sessions. In fact, during the first eleven ISS Expeditions, only for 2 short periods during Expeditions 3 and 4 were all three U.S. onboard exercise devices (Cycle
Egometer with Vibration Isolation System [CEVIS],
Treadmill with Vibration Isolation System, and iRED) capable of being used under nominal conditions (Figure 6-10). The almost continuously suboptimal availability of exercise equipment likely has reduced maintenance of crew physical fitness. studies from 120 to 170 days in duration. Despite these shortcomings, lean tissue mass data collected by means of dual-energy x-ray absorptiometry (DEXA) before and after flight compares favorably with data from NASAMir, and the total body and leg losses are in fact less than seen during NASA-Mir or during three separate
bed rest studies of similar durations in the range of 20–170 d (Figure 6-11). However, the news is not entirely good since knee extensor and knee flexor strength losses in long-duration crewmembers after flights aboard Mir and ISS This summary addresses nearly exclusively those investigations in which the effects of mechanical unloading on antigravity muscles were examined, and the consequent tissue remodeling at the structural and biochemical levels. Additionally, the relative success of various countermeasures is examined. Decreases in skeletal muscle size and function have been reported since humans first began to explore space. Spaceflight results in the loss of
lean body mass as determined by body composition measurements. Urinary
amino acid and nitrogen excretion, both indirect measures of catabolism of lean body mass, are elevated during both brief spaceflights. Direct measurement of protein synthesis during spaceflight using 15N-glycine incorporation as a marker revealed an increase in whole-body protein synthesis rates. These results indicated that the significant decrease in lean body mass observed after spaceflight must be associated with a significant increase in protein degradation rates More recently, these findings have been confirmed by direct volume measurements (by magnetic resonance imaging [MRI] of astronauts on the Space Shuttle and of Russian cosmonauts and U.S. astronauts after tours of duty on the Mir space station. Notably, postflight muscle sampling was carried out within 2–3 hours of landing, which minimized the effects of reambulation on the muscle. Analysis of the muscle biopsy samples with a variety of morphologic, histochemical, and biochemical techniques indicated that the myofiber CSA was significantly decreased after spaceflight; that atrophy was greatest in Type IIB myofibers, followed by Type IIA and then Type I myofibers; that expression of Type II
myosin heavy chain (MHC) protein was significantly increased, with an apparent decrease in the amount of Type I MHC protein expressed; and that the number of myonuclei per mm of myofiber length was significantly decreased in Type II myofibers after 11 days of spaceflight. In contrast to these findings, analysis of needle biopsy samples from cosmonauts, conducted by the Institute for Biomedical Problems after 76- and 180-day flights, indicated a large degree of individual variation in the extent of myofiber atrophy, with the decrease in myofiber CSA ranging from about 4% to 20%. This variation was attributed to variations in compliance with exercise countermeasures by individual cosmonauts during the flights. More recent muscle biopsy studies have indicated that despite consistent decreases in myofiber CSA in the m. soleus and m. gastrocnemius after spaceflight, MHC expression does not seem to shift, as was previously described by Zhou et al. which seems to be paralleled by a reduction in the overall electrical activity of the muscle after spaceflight, raises the possibility that neuron-derived factors that play a role in the growth or maintenance of skeletal muscle may be disrupted. The hypothesis that microgravity causes a fundamental alteration in motor control has also been suggested. Studies conducted at JSC by the Exercise Physiology Laboratory showed that two-legged muscle power declines considerably more than can be explained by the loss in muscle mass alone. Additionally, the loss of explosive leg power was associated with a substantial reduction in the
electromyography (EMG) activity of the m. rectus femoris, m. vastus lateralis, and m. vastus medialis. These investigators concluded that microgravity induced a basic change in motor control and coordination such that motor activation of extensor muscles was reduced. Similar observations have been made after long-duration spaceflight on Mir and ISS. Evidence exists that exercise strategies are effective in attenuating muscle strength loss in bed rest. Bamman et al. preserved pre-bed rest muscle strength of the thigh and calf in subjects who performed resistive exercise with loads equivalent to 80–85% of their pre-bed rest strength (Repetition maximum test). Protection of muscle volume occurred through the maintenance of protein synthesis, which also likely influenced muscle strength. Similarly, Akima et al. were able to maintain isometric peak torque in subjects who performed daily maximal isometric contractions of the knee extensors during 20 days of bed rest. Using an aggressive resistive exercise training protocol, Shackelford et al. preserved isokinetic muscle strength and observed substantial increases in isotonic muscle strength over the course of 89 days of bed rest in exercising subjects. Using a flywheel resistive exercise device, Alkner and Tesch prevented the loss of muscle mass and strength in the thigh and attenuated the losses in the calf. The similarity in skeletal muscle responses during spaceflight and bed rest were elegantly demonstrated by Trappe and colleagues A reduction in the size or volume of the ambulatory muscles accounts for most of the decrease in lean body mass after bed rest. This decrease correlates with a significant reduction in muscle protein synthesis. Decreases in muscle volume after bed rest were paralleled by decreases in muscle strength and endurance, as evidenced by significant decreases in angle-specific torque, isokinetic muscle strength, and fatigability. Similar losses in muscle volume, paralleled by decreases in muscle strength and endurance, have been observed after unilateral lower-limb suspension. Dry immersion, a whole-body-unloading paradigm with the added advantage of mimicking the reduced proprioceptive input encountered during spaceflight, also brings about reductions in muscle volume, strength, endurance, electrical activity, and tone. At the structural level, the loss of muscle volume in these models correlates with a significant decrease in CSA of both Type I and Type II myofibers. In general, Type II myofibers seem to be more likely to atrophy than do Type I myofibers during short-term unloading, with no significant myofiber type shifting being observed, However, prolonged bed rest (greater than 80 days) does significantly change the number of MHC hybrid fibers observed in the soleus muscle. Immobilization by limb casting does not seem to reduce the relative proportions of muscle-specific proteins, such as carbonic anhydrase II and myoglobin, over that predicted by the overall decrease in muscle protein synthesis. In contrast, experimental evidence suggests that the specific activity of muscle enzymes involved in oxidative metabolism, such as pyruvate dehydrogenase, is decreased by cast immobilization. A similar reduction in the activity of citrate synthase, but not phosphofructokinase, has been detected in the vastus lateralis, indicating a significant impairment of the oxidative capacity in this muscle after unilateral limb suspension. The differences observed between cast immobilization and unilateral limb suspension or bed rest protocols may reflect the former being a better model of muscle atrophy induced by hypokinesia and the latter two being better models of muscle atrophy induced by muscle hypodynamia. The latter situation more closely resembles the actual conditions experienced by crewmembers during spaceflight, namely removal of mechanical loading without a reduction in limb mobility. However, it is apparent that although ground-based unloading models are useful in studying the effects of microgravity on skeletal muscle, no single terrestrial model system produces all the physiological adaptations in skeletal muscle observed as a consequence of spaceflight. Again, the decreases in muscle volume and myofiber CSA observed in these ground-based analogs of spaceflight bring about changes in the neuronal-activation patterns of the unloaded muscles, including decreased electrically evoked maximal force, reduced maximal integrated electromyography, Certainly such decreases in the neural drive in unloaded muscle play a role in the atrophic response. As in spaceflight, adaptations to unloading can be observed after short-duration bed rest. For example, after 20 d of bed rest, volume of quadriceps muscle decreased by 8%, hamstrings decreased by 10%, and plantar flexor muscles were reduced by 14%. a 26% ± 7 decline in the CSA of the calf muscle was observed. This rate of decline is consistent with earlier measurements in which after 90 days of bed rest, a roughly 15% decline in quadriceps and hamstring muscle volume measured by MRI scans were noted in two subjects. The authors reported no explanation for this discrepancy between the proportion of reduced strength relative to the loss of mass, and also stated that no previous studies in the literature had made these concurrent strength/volume measurements in the hip musculature. Some general conclusions that can be drawn from the above human studies are as follows. First, terrestrial unloading models produce selective atrophy in the muscles of the lower limbs, especially the anti-gravity muscles; second, this response is greater in the extensor muscles than in the flexor muscles; third, muscle atrophy occurs quickly (within 7–14 days) in response to unloading; fourth, loss of muscle mass is paralleled by decrements in muscle strength and endurance, but strength losses typically are greater than volume losses; fifth, if atrophy is specific to a myofiber type within these muscles, it seems to be Type II myofibers; and sixth, terrestrial unloading does not seem to produce a slow-to-fast shift in absolute myofiber characteristics but does alter the expression of MHC isoforms in human muscle so that an increase in MHC hybrid myofibers is observed, resulting in a faster phenotype. Other research findings exist that relate peripherally to this risk description that should remain associated with it. The physical inactivity and muscle unloading occurring in association with spaceflight can result in a decrease in muscle mass, which in turn may be associated with an increased susceptibility to insulin resistance (glucose intolerance). While this association is quite clearly documented in bed rest studies, the association is not yet solidified for spaceflight. Additionally, the major countermeasure to muscle atrophy is exercise, and it should be appreciated that crewmembers chronically exposed to the microgravity environment may develop impaired body temperature regulation during rest and exercise that may lead to heat strain and injury. These are discussed more fully in the paragraphs that follow. After short-duration spaceflights, Soviet cosmonauts were observed to have elevated serum insulin levels that persisted up to 7 d after landing. In the first 28 U.S. Space Shuttle flights (2–11 d duration), serum insulin levels (n = 129) were elevated by 55% on landing day compared to before flight. Russian space life science investigators reported two-fold or greater increases in insulin levels in three cosmonauts within 1 day after they returned from a 237-d flight. The associated finding of elevations in both insulin and blood glucose (12% on landing day compared to preflight levels in 129 Space Shuttle crewmembers on flights of 2–11 d duration) may indicate an acquired decreased tissue sensitivity to insulin associated with spaceflight. Ground-based bed rest studies simulating weightlessness in humans have shown an increased insulin response to glucose tolerance tests. In such studies, plasma insulin levels have increased up to four-fold compared to those of control subjects, and blood glucose levels exceeded those of the controls 2 h after glucose loading. In a well-designed 7-d bed rest study, insulin action on both whole-body glucose uptake rate and leg glucose uptake rate was investigated. It was concluded that the inactive muscle of bed rested subjects was less sensitive to circulating insulin. However, in a study of four Space Shuttle astronauts by the same investigators, in which glucose tolerance tests were performed 15 d before launch, on flight day 7, and on postflight days 2 and 15, increases in the concentrations of insulin, glucose, and Cpeptide in in-flight samples were observed, but the changes were not significantly different from the preflight and postflight values. The investigators concluded that 7 d of spaceflight did not confirm the assumption that microgravity exposure leads to impaired glucose tolerance. However, the brief (7 d) exposure to microgravity may have been insufficient in duration to induce statistically significant changes, and thus additional studies on crewmembers from long duration missions are needed to confirm these findings. Human expenditure of energy results in the generation of heat. The body heat generated by normal activities, and particularly by exercise, triggers homeostatic regulatory mechanisms with the goal of maintaining body core temperature within its relatively narrow, safe physiologic range by means of vasoregulation and diaphoresis. The weightlessness environment of spaceflight may impair heat dissipation by reducing evaporative and conductive heat exchange. Microgravity and spaceflight may perturb the body's thermoregulatory mechanisms by altering the work efficiency, metabolic rate, or circadian rhythms of heat production. Additionally, human space travelers are often not well hydrated, have a 10–15% decrease in intravascular fluid (plasma) volume, and may lose both their preflight muscular and cardiovascular fitness levels as well as their thermoregulatory capabilities. As a result, they may become less heat-acclimated or may acquire an altered thermal sensitivity. Alterations in thermoregulation in association with spaceflight could significantly affect a variety of spaceflight-associated activities including exercise as a countermeasure to muscle atrophy, cardiac deconditioning, and bone loss; extravehicular activity (EVA); and vehicle landing and egress. EVA suits and launch and entry or
advanced crew escape suits (ACES) worn by ISS and Shuttle crewmembers are designed to provide an impermeable barrier between the wearer and the external environment. To compensate for lack of heat exchange through the fabrics of these suits, the EVA suit provides both liquid (conductive) and air (convective) cooling, while a liquid cooling garment is worn under the ACES in addition to a hose connection to forced orbiter cabin air. Thus, crewmembers with altered thermoregulatory capabilities are at even greater risk should failure of the cooling systems of these garments occur. Manifestations of altered thermoregulation include increased heart rate and body temperature during exercise, decreased work capacity and endurance, decreased postflight orthostatic tolerance, decreased cognitive ability, and a delay in recovery of exercise capacity and endurance after flight. Thermoregulation has been studied in association with both spaceflight and 6° head-down-tilt bed rest. To date, there have been no direct measurements of heat balance during in-flight exercise sessions. In the only spaceflight study, submaximal exercise and thermoregulatory responses were recorded before flight and at 5 d after landing in two crewmembers who completed a 115-d mission. These flight experiments are complemented by numerous ground-based research studies that focused collectively on the topics described below. Most importantly, all of the data reported in this summary are derived from animal cohorts in which the control animals were studied from a synchronous vivarium group of the same age, strain, and gender, and the analyses were performed at the same time as that of the experimental groups. The provided information is based entirely on peer-reviewed experiments as detailed in the bibliography provided.
Activity patterns during spaceflight While recorded observations during spaceflight are less extensive in rodents (due to fewer flight missions with opportunities for astronauts or payload specialists to observe them), the available data suggest that rodents rely less on the hindlimbs for executing most movement patterns (as is the case for humans). During spaceflight, their ankles appear to assume a plantar flexed position that may reduce the passive tension (force) imposed on the triceps surae group, of which the anti-gravity slow-twitch soleus muscle is a chief component. A similar posture has been observed in the ground-based analog of HS. This posture is thought to affect the residual tension placed on this muscle group in the absence of a normal weight-bearing state, that is, the ankle plantar flexor muscle group becomes truly unloaded. While electromyographic studies on adult rodents have not been conducted during spaceflight, studies performed on rodents during chronic HS indicate that only a transient reduction occurs in electrical activity of the ankle plantar flexor muscles (soleus and medial gastrocnemius). This pattern of activity is consistent with the posture of the muscle and the maintenance of muscle mass during the 28-day time frame of the experiment. That is, the EMG activity was well maintained, while the ongoing atrophy was maintained. These findings reinforce the notion that it is the mechanical activity rather than the electrical activity imposed on the muscle that is essential to maintaining physiological homeostasis.
Activity patterns in early recovery from spaceflight When animals return from spaceflight of even short duration (days), their basic activity patterns are altered. The center of gravity in rats is much lower than normal. They no longer support their body weight and initiate movement off the balls of their feet, and the ankle joint assumes an exaggerated dorsiflexed position. Additional reviews on this topic have been published. The collective observations clearly show that these types of muscle undergo significant reductions in muscle mass (muscle weight) along with a concomitant loss in total protein and myofibrillar (the fraction that is composed of the contractile machinery of structural proteins) protein content of the targeted muscles. In some experiments, it has been reported that the myofibrillar fraction can be degraded to a greater extent than other muscle fractions. As a rule, regardless of the muscle, the larger
fibers, whether fast or slow, are more sensitive to the unloading stimulus than their smaller counterparts. This transformation is largely manifested in the expression of hybrid fibers, in which both slow MHC and either fast type IIx or fast type IIa MHC become simultaneously co-expressed. More recent studies on this topic clearly suggest that the type IIx MHC, which is a faster isoform than the IIa type, is more abundantly expressed. From these observations it is apparent that the myofibrillar fraction, which is a key component of the muscle, is targeted for net degradation (as noted above) for two reasons: • degradation of this fraction allows smaller-diameter fibers to become manifest to meet the reduced requirements for force generation, and • the unraveling of the myofibrillar system allows faster MHC isoforms to become incorporated into the contractile machinery to replace the slower ones so that the muscle is able to function more effectively under a reduced state of gravitational loading. Providing further insight is the observation that the unloading state of spaceflight and of HS also increases the expression of fast type II
sarcoplasmic reticulum (SR) ATPase-driven calcium pumps (SERCA II) while repressing the slower type I SERCA calcium pump. Since calcium cycling is used to regulate fiber activation and relaxation, the SR component of the muscle fiber controls the synchrony of contraction-relaxation processes. Since calcium cycling and crossbridge cycling are the two major systems that account for the vast majority of the energy expended during muscle contraction to support movement, when this property of the muscle is switched to a faster system the muscle can function more effectively in the unloaded environment. However, when the muscle encounters environments with a high gravitational stimulus, the faster properties are inherently less economical in opposing gravity and thus the muscle fibers become more fatigable when contracting against a load for long durations. These observations are consistent with the results of studies focusing on mitochondrial function after 9 days of spaceflight in which no reduction in the capacity of skeletal muscle mitochondria to metabolize pyruvate (a carbohydrate derivative) reported that in isolated single-fiber analyses, deficits in force generation capacity were found along with a reduced sensitivity to calcium stimulation. Similar observations occurred for both slow and fast ankle extensor fibers after 14 days of spaceflight. This study focused on the force-generating aspects of muscle fibers. It appears that only two additional studies have been conducted to examine the effects of spaceflight on rodent skeletal muscle functional properties using a more comprehensive set of analyses. One project was carried out for 6 days Similar findings have been observed using comparable analytical approaches involving the HS model. Taken together, the findings clearly indicate that when skeletal muscles, especially those having a large proportion of slow myofibers, undergo both atrophy and remodeling of the contractile phenotype, the functional capacity of the muscle is reduced along with its ability to sustain work output. If a sufficient mass of muscle tissue across several key muscle groups were similarly affected, this would most likely impair the fitness of the individual when challenged with moderate-intensity exercise scenarios.
Are atrophied muscles vulnerable to injury Riley and associates have provided an excellent synopsis of the structural integrity of mammalian muscle during the early stages after return from spaceflight. Their findings suggest that in atrophied slow types of skeletal muscle, there is no evidence of fiber damage when the muscles are taken from animals euthanized and processed during spaceflight. However, observations suggest that during the first 5–6 hours after spaceflight (the earliest time point at which the animals can be accessed), edema occurs in the target anti-gravity muscles such as the soleus and the adductor longus (AL). This alteration, in combination with a smaller amount of mRNA substrate, collectively contributes to a reduction in the net capacity for protein synthesis. Occurring simultaneously with this process is the up-regulation of a set of genes that encode proteins that play a regulatory role in augmenting protein degradation. These include the myostatin gene, As a result of the reduction in net capacity for protein synthesis and the augmentation of protein degradation, a net loss of muscle protein in the muscle fiber occurs along with a change in the relative proportion of the MHC protein content, since available findings show that the faster MHC genes are up-regulated during muscle atrophy. However, in pre- and postflight analyses of single fibers, slow fibers in both the slow-twitch soleus and triceps muscles underwent greater atrophy and reductions in force and power production than fast-twitch fibers. Also, transformations in the myosin heavy chain profile indicated that there was a greater level of hybrid slow/fast fibers in the two different muscle groups. Immobilization of the triceps muscle group produced similar responses, but the magnitude of change was much less than that in the spaceflight animals. These alterations were chiefly manifested in modified load-related cues as reflected in the altered relative recruitment bias of flexor muscles versus extensors and fast versus slow motor unit pools. In an additional flight study (Cosmos Flight 2229) involving two rhesus monkeys, EMG recordings were obtained before, during, and after spaceflight. These experiments were unique in that recordings obtained during spaceflight revealed a preferential shift in recruitment patterns favoring the fast medial gastrocnemius versus its synergistic slow soleus muscle, that is, the normal recruitment pattern was reversed; and this alteration was maintained well into the recovery stage after spaceflight, further suggesting a reorganization of the neuromotor system during and immediately after exposure to microgravity. Thus, it is apparent that skeletal muscle fibers of humans, monkeys, and rodents share similar patterns of myofiber alterations that, in the case of monkeys and humans, are also linked to altered motor performance in response to different states of unloading, reduced usage, and return to an Earth gravitational environment. ==Computer-based simulation information==