and timelines for the two studies were identical, which allowed direct comparisons between a spaceflight and a bed rest study of equivalent duration. calf muscle strength was measured before and on days 2, 8, and 12 of spaceflight and bed rest as well as on days 2 and 8 after spaceflight and bed rest in the two investigations. muscle biopsies were obtained before and within 3 hours after spaceflight (m. gastrocnemius and m. soleus) and bed rest (m. soleus) just before reloading. after 17 days of spaceflight or bed rest, no significant measurable changes occurred in maximal isometric calf strength, force-velocity characteristics, myofiber composition, or volume in the calf muscles studied. since loss of skeletal muscle strength is an expected finding in both spaceflight and bed rest, the investigators concluded that the testing protocol utilized during both studies must have provided sufficient resistance exercise to prevent losses in muscle strength and changes in morphology. some general conclusions that can be drawn from the data gathered from astronaut/cosmonaut studies are as follows. first, loss of muscle mass is most prevalent in the antigravity muscles such as the soleus; second, the atrophic response to short-term spaceflight does not seem to be specific to myofiber type; and third, myosin heavy chain (mhc) isoform expression does not seem to shift from type i mhc to type ii during short (< 18-day) spaceflights. ground-based analog studies several ground-based paradigms have been used to emulate the effects of microgravity unloading on human skeletal muscle, including complete horizontal or 6° head-down-tilt bed rest, dry immersion, and unilateral upper- and lower-limb unloading with or without joint immobilization. in general, skeletal muscle responses to unloading have been similar in all of these models. although no perfect simulation of crew activities and the microgravity environment can be adequately achieved, adams and colleagues have suggested that bed rest is an appropriate model of spaceflight for studying skeletal muscle physiologic adaptations and countermeasures. bed rest unloading causes a significant loss of body nitrogen and lean body mass. 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. horizontal and 6° head-down-tilt bed rest protocols of various durations (7 days, 14 days, 30 days, 5 weeks, or 17 weeks) have resulted in significant reductions in lower-limb muscle volume as measured by mri, ranging from a 30% loss in the ankle extensor muscles to a 12% loss in the plantar flexors (gastrocnemius and soleus). 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, although alterations in total muscle mhc protein isoform expression have been reported. 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. absent from human analog studies are the unique operational and psychological stressors associated with spaceflight that exacerbate the physiological changes resulting from muscle unloading. 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, and neuromuscular junction dysfunction. 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%. during a longer, 89-d bed rest, greater reductions in muscle volume in the quadriceps (−15%), hamstrings (−13%), soleus (−29%), and gastrocnemius (−28%) were reported. in a 90-day bed rest trial, 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. reductions in muscle strength were also demonstrated in these studies. bamman and colleagues observed losses of 18, 17, and 13% in concentric, eccentric, and isometric plantar flexor peak torque, respectively, after 14 d of bed rest, and akima and his co-investigators observed a 16% decrease in knee extensor isometric torque after 20 days of bed rest. although not specifically reported, subjects in an 89-day bed rest trial experienced significant reductions in isokinetic torque in the lower body, with the greatest losses in the knee extensors (−35%). this study also used isotonic testing (1rm), and mean losses ranging from −6 to −37% were observed; reductions in adductor, abductor, and leg press strength were on the order of ~25–30%. in an earlier 90-day bed rest trial, leblanc and colleagues observed losses of 31% in knee extension strength and 15% in knee flexion strength. few studies have reported changes in the ab/adductor or the flexor/extensor muscles of the hip. shackelford et al. reported that isotonic strength decreased by about 25% in the adductors, but only a 6% decrease in the hip flexors was demonstrated after 17 weeks of bed rest. after 55 days of bed rest, berg et al. reported that a 22% reduction in isometric hip extension occurred, although the extensor muscles in the gluteal region decreased in volume by only 2%. 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