physiological effects in space physiological effects in space even before the very beginning of human space exploration, serious and reasonable concerns were expressed about exposure of humans to the microgravity of space due to the potential systemic effects on terrestrially-evolved life forms adapted to earth gravity. unloading of skeletal muscle, both on earth via bed-rest experiments and during spaceflight, result in remodeling of muscle (atrophic response). as a result, decrements occur in skeletal muscle strength, fatigue resistance, motor performance, and connective tissue integrity. in addition, there are cardiopulmonary and vascular changes, including a significant decrease in red blood cell mass, that affect skeletal muscle function. this normal adaptive response to the microgravity environment may become a liability resulting in increased risk of an inability or decreased efficiency in crewmember performance of physically demanding tasks during extravehicular activity (eva) or upon return to earth. in the us human space program, the only in-flight countermeasure to skeletal muscle functional deficits that has been utilized thus far is physical exercise. in-flight exercise hardware and protocols have varied from mission to mission, somewhat dependent on mission duration and the volume of the spacecraft available. collective knowledge gained from these mission has aided in the evolution of exercise hardware and protocols designed to minimize muscle atrophy and the concomitant deficits in skeletal muscle function. russian scientists have utilized a variety of exercise hardware and in-flight exercise protocols during long-duration spaceflight (up to and beyond one year) aboard the mir space station. on the international space station (iss), a combination of resistive and aerobic exercise has been used. outcomes have been acceptable according to current expectations for crewmember performance on return to earth. however, for missions to the moon, establishment of a lunar base, and interplanetary travel to mars, the functional requirements for human performance during each specific phase of these missions have not been sufficiently defined to determine whether currently developed countermeasures are adequate to meet physical performance requirements. research access to human crewmembers during space flight is limited. earth-bound physiologic models have been developed and findings reviewed. models include horizontal or head-down bed rest, dry immersion bed rest, limb immobilization, and unilateral lower-limb suspension. while none of these ground-based analogs provides a perfect simulation of human microgravity exposure during spaceflight, each is useful for study of particular aspects of muscle unloading as well as for investigation of sensorimotor alterations. development, evaluation and validation of new countermeasures to the effects of skeletal muscle unloading will likely employ variations of these same basic ground-based models. prospective countermeasures may include pharmacologic and/or dietary interventions, innovative exercise hardware providing improved loading modalities, locomotor training devices, passive exercise devices, and artificial gravity either as an integral component of the spacecraft or as a discrete device contained within it. with respect to the latter, the hemodynamic and metabolic responses to increased loading provided by a human-powered centrifuge have been described recently. historical overview 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. figure 6-1: the exercise device used on some apollo missions 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. dietlein has provided a concise synopsis of the findings. 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. the studies completed during apollo, although less than optimal, left no doubt that a decrement in exercise tolerance occurred in the period immediately after landing, although it is believed that such decrements were not present during surface eva. it seems likely that multiple factors are responsible for the observed decrements. lack of sufficient exercise and development of muscle disuse atrophy probably contributed. catabolic tissue processes may have been accentuated by increased cortisol secretion as a consequence of mission stress and individual crew member reaction to such stress. additional factors associated with the return to earth's gravity may also be implicated. this, the observed diminished stroke volume (cardiac output) is certainly contributory and, in turn,