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. normal heart rates were observed for both crewmembers during supine exercise for 20 min each at 20% and 65% of vo2max. however, during postflight (five days after landing) testing, exercise was voluntarily discontinued after only 8–9 min of supine exercise at the 65% of vo2max level for the two crewmembers when they both experienced difficulty in maintaining pedaling frequency and complained of leg fatigue, and their heart rates exceeded the highest recorded preflight levels. both crewmembers exhibited a more rapid increase in body core temperature during the shorter postflight exercise session than during the preflight session; it was concluded that heat production was not altered but that impairment of heat dissipation due to altered vasodilatory and sweating responses were responsible for the increased rate of rise in the core body temperature. adequate energy (caloric) intake is a necessary requirement for humans living and working in space, and much attention has been focused on this requirement. less effort has been spent on understanding how the caloric heat generated by energy expenditure is handled by humans whose physiologic responses to heat may be altered in the unique physical environment of spaceflight. such studies should be considered at a higher level of priority for future human space missions. recently applied models may be of use in providing a better understanding of the magnitude of this associated risk. experimental animal studies this section summarizes the studies that have been conducted on animal subjects (such as rodents and non-human primates) that have been exposed either to spaceflight or (in the case of rodents) to the well accepted ground-based analog of hind-limb suspension (hs) to ascertain the effects of unloading states on the properties of muscle mass, strength, and endurance. the results presented herein overwhelmingly corroborate the body of evidence that has been reported on human subjects in the preceding sections of this report. importantly, through the use of more cellular and molecular analyses, greater insights have been obtained into the underlying mechanisms associated with these alterations in muscle structure and function. since the majority of evidence concerning the effects of spaceflight on mammalian skeletal muscle has been derived from rodent studies, the information provided here is focused mostly on the rodent model. it is important to point out that the structure and function of rodent skeletal muscle are nearly identical to those of human skeletal muscle. for example, rodent muscle is composed of the same general fiber-type profile and is sensitive to the same environmental (mechanical, hormonal, metabolic) cues observed for human muscle. thus, the information summarized below provides credence to the data base derived from human subjects. however, it is important to point out that one primary advantage of the rodent model is that adaptive changes that occur in both species unfold in a much shorter time frame in rodents than in humans (hours to days versus days to weeks), making it possible to predict long-term changes in human skeletal muscle based on the shorter absolute time frame of the studies performed on rodents. another important consideration in the context of animal research during spaceflight is that one can perform a straightforward experiment in which there is no requirement to provide some type of countermeasure intervention as there is for humans, and can thereby avoid the introduction of a confounding variable in ascertaining the true effects of spaceflight on a wide range of physiological variables. also, given the remarkable agreement in the quantitative and qualitative nature of the findings observed in the spaceflight studies versus those obtained from ground-based hs studies, we have chosen to combine and integrate significant portions of the data that have been gathered in the last 25 years. this rodent data base in space life sciences research includes 14 flight experiments with 8 sponsored by the russian cosmos program and 6 sponsored by nasa space life sciences (sls) and space transportation system (sts) missions. 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. movement for most voluntary activities is much slower and more deliberate (the animals cover smaller distances per unit time), and the animals spend significantly less time in bipedal stances. furthermore, the rodents use their tails for basic support to a greater degree, based on observations by the investigators. thus, rodent motor skills and basic locomotor capability have less fidelity and capacity during posture maintenance and locomotion during the early stages of recovery; however, by 9 days after flight the activity properties return to those seen in normal conditions. effects of spaceflight and hindlimb suspension on muscle mass, protein content and gross morphological properties of skeletal muscle considerable information has accumulated covering a large number of spaceflight and hs experiments that span a time frame of ~4 to 22 days for spaceflight and from 1 to 56 days for hs. these experiments have primarily focused on extensor muscles used extensively for postural support and locomotor activity. the review by roy, baldwin, and edgerton provides one of the most comprehensive reviews on rodents in the space environment. 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. the general pattern demonstrates that a rapid loss in muscle weight and net total and myofibrillar protein content (concentration (mg/g x muscle weight) occurs during the first 7–10 days of unloading and this is followed by a more gradual loss in these constituents. the net result is that between 25 and 46% of the muscle mass can be lost in antigravity muscles of the lower extremity such as the soleus (sol; a calf muscle) and vastus intermedius (vi; a deep layered quadriceps muscle), which are composed mostly of the slow type i myofibers containing the slow myosin heavy chain (mhc) protein. mhc is the most abundant protein expressed in striated muscle; and this structural / regulatory protein serves as the motor protein that regulates, in synergy with its companion protein actin, the contraction process that derives the force, work, and power generation that is necessary for the muscle groups to bring about both movement and stabilizing types of activity (posture). it is also important to point out that fast-twitch synergistic muscles (expressing fast isoforms of mhc) are also targeted, but these muscles and their fibers are apparently not as sensitive to the unloading stimulus as the slower types of muscle are. compared to both the slow and fast types of muscle, atrophy of the corresponding joint flexors, for example the tibialis anterior and extensor digitorum longus muscles in the leg, is markedly less. histochemical and immunohistochemical analyses at the single-fiber level clearly show that the atrophic process seen at the gross level is due to a reduction in the diameter of the affected myofibers of which the individual muscles are composed. these observations show that the slow type of fiber is more sensitive than the faster types of fiber, which is consistent with the gross muscle mass determinations. 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. muscle fiber phenotype remodeling in response to spaceflight and hind-limb suspension accompanying the atrophy process noted above are the important observations that many (but not all) of the slow fibers in primarily antigravity-type muscles (such as soleus and vi) are also induced to express fast myosin isoforms. 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. these observations suggest that the slow mhc is targeted for degradation, evidenced by the net loss in slow mhc in the atrophying muscle (fibers), while at the same time, according to premrna and mrna analyses, up-regulation of the faster mhc genes by transcriptional and/or pretranslational processes occurs. 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