A potentially serious consequence of weightlessness is the deconditioning of such physiological systems as the cardiovascular complex. On Earth, the heart must operate against gravitational pressure to sustain blood flow and proper functioning of the cardiovascular system. Under zero gravity (0 g) conditions, no such hydrostatic pressure gradient exists. Consequently, the heart lessens its pace to achieve an equilibrium appropriate to decreased demands. Reduced output of the heart, decreased heart rate, decreased heart size, and diminished blood volume regulation result (Berry, 1973b).
Diminished loading inherent in weightlessness is also a significant problem as it affects the musculoskeletal system. Reduced weight bearing in space leads to bone "disuse" symptoms including loss of calcium, nitrogen, and phosphorus; decreased bone size and volume; and formation of urinary stones (Berry and Catterson, 1967; Hattner and McMillan, 1968; Biryukov and Krasnykh, 1970; Mack, 1971). Decreased muscle tone and strength, weakened reflexes, and decreased tolerance for physical work are further negative consequences of 0g.
Problems of physiological deconditioning were noted during the 28 , 59 , and 84 day Skylab missions (Johnston and Dietlein, 1977) and during the recent Soviet missions of 175, 185, and 211 days (Toufexis, 1983). Given that significant alterations in biomedical functioning occur during spaceflight, it is crucial that, where possible, Earth based models be developed to study these changes. Current knowledge suggests that a hypokinetic state is the most appropriate ground based method with which to study many of the effects of prolonged weightlessness. Data have been generated using plaster cast immobilization (Dietrick, Whedon, and Shorr, 1948; Billman, Teoh, Dickey, and Stone, 1981; Dickey, Billman, Teoh, Sandler, and Stone, 1982); chair rest (Lamb, Johnson, and Stevens, 1964; Lamb, Stevens, and Johnson, 1965); confinement (Henna and Gaito, 1960; Alluisi, Chiles, Hall, and Hawkes, 1962; Lamb, Johnson, Stevens, and Welch, 1964; Kurash, Andzheyevska, and Gurski, 1980); dehydration (Dunn, 1978; Dunn and Lange, 1979; Dunn, Leonard, and Kimzey, 1981); water immersion (Gauer, 1975; Epstein, 1978); "dry" immersion (Gogolev, Aleksandrova, and Shul'zhenko, 1980); partial body support (Morey, 1979; Jordan, Crownover, Sykes, Schatte, Simmons, and Jordon, 1980); and  clinostatic rotation (Cogoli, Vallucki Morf, Mueller, and Briegleb, 1980). The major source of information, however, has come from studies of bedrest (see Birkhead, Blizzard, Issckutz, and Rodahl, 1964; Miller, Johnson, and Lamb, 1964, 1965; Chase, Grave, and Rowell, 1966; Vogt, Mack, and Johnson, 1966, 1967; Lynch, Jenson, Stevens, Johnson, and Lamb, 1967; and the Ames Research Center studies detailed in later sections of this chapter).
The lack of activity imposed by recumbency effectively simulates many of the effects that weightlessness produces1 (see Berry, 1973b, for comparative review). Bedrest results in reduced hydrostatic pressure and a relative lack of stress upon the body similar in many ways to the conditions of 0 g. Within 24 to 48 hr following recumbency, there is a loss of fluid volume when an initial shift of volume from the lower extremities to the chest is interpreted by central mechanoreceptors as a relative increase in volume. This perceived volume increase triggers diuresis, resulting in fluid loss. Fluid loss is one of the reasons for body weight losses observed during prolonged bedrest (and spaceflight). It is also a factor in the deconditioning of the cardiovascular system, since decreased blood volume along with decreased blood pressure results in diminished reactivity of vessels.
Bedrest also simulates the effects of weightlessness on the musculoskeletal system. When the human body is maintained in the horizontal position, gravitational forces do not exert pressure upon the support structure in the same way as experienced in the vertical position. Consequently, muscles tend to atrophy from disuse and bones tend to demineralize from lack of stress. These factors combine with cardiovascular and metabolic alterations to decrease work tolerance and capacity.
Since recumbency produces many of the biomedical changes which occur in space, bedrest would appear to be a valid model for the study of behavioral changes likely to occur in flight. Unfortunately, relatively few experiments have explored this possibility. Furthermore' existing studies have produced contradictory data and have experienced procedural problems. For example, Ryback, Trimble, Lewis, and Jennings (1971a) were among the first investigators to publish performance data obtained from prolonged (5 wk) bedrest. They employed four basic test units to assess psychomotor  performance during pre and post recumbency. The tasks employed measured such factors as hand eye coordination, reaction time, vigilance, short term visual memory, hand and limb steadiness, auditory coding, etc. Hand eye coordination was the only factor that decreased significantly during post bedrest recumbency relative to pre bedrest values. Following bedrest, subjects were not as proficient in inserting a stylus into various hole sizes while attempting to avoid touching the edges of the holes. However, in a second study (Ryback, Lewis, and Lessard, 1971b) subjects tested in a reclining position (rather than in the standing position used during the first study) did not demonstrate decrements in reaction time and hand steadiness as found in the original experiment. Apparently, instability in the vertical position, rather than any biomedical or psychological effects, was the main reason for the decrements in performance observed in the first study. Additional tasks used in the second study involving measures of speed and accuracy of movement also failed to show consistent changes. The only significant differences found involved measures of neuromuscular strength of handgrip. Handgrip for the nondominant hand declined significantly from pre bedrest levels among subjects not exercising during bedrest. This increment was most pronounced after the third week of hypokinesis. However, an earlier study (Bourne, Nandy, and Golarz de Bourne, 1968) has shown that little change in handgrip strength occurs even after 60 days of bedrest, at least when the dominant hand is measured.
More recent studies of bedrest subjects conducted at Ames Research Center have also failed to demonstrate consistent group changes in performance. For example, Winget, De Roshia, and Sandler (1979) studied 35 to 55 yr old females exposed to 9 days of bedrest. Performance was assessed using an ATC 510 flight simulator modified to permit operation while the subject was in the bedrest position. Daily test scheduling was arranged so that trials occurred both during "peak" and "trough" portions of heart rate and bodytemperature cycles. Although decrements in performance were observed, there were no statistically significant group differences between pre bedrest, bedrest, or post bedrest periods. Apparently, while some individual subjects exhibited marked changes during the study, considerable variability in performance across subjects tended to mask group effects. Other studies reported by Winget and his colleagues (Chapman, Winget, Vernikos Danellis, and Evans, 1975; Chapman, Winget, and Vernikos Danellis, 1976) have noted similar difficulties for other age groups in isolating performance decrements.
 Data from these studies are still under analysis and few detailed reports are available in the literature. It is hoped that more thorough statistical assessment may yield significant predictors of changes in bedrest performance.
Other investigators have failed to demonstrate significant changes in psychomotor performance following bedrest. Jex, Peters, Di Marco, and Allen (1974) tested eight carrier qualified Navy Reserve A 7 pilots before and after 10 days of bedrest. Using controlstick tracking tasks, no differences in performance were observed when pre and postrecumbancy measures were analyzed. Likewise, Storm and Giannetta (1974), using tests of complex tracking performance, eye hand coordination, and problem solving ability, found no significant effects due to hypokinesis among airmen subjected to 2 wk of absolute bedrest.
If performance does not deteriorate at the psychomotor level, alterations could still occur at the perceptual or cognitive level. Thus far, only limited research has been devoted to these topics. Ryback et al. (1971b) did observe a reduced range of ideas on a measure taken during bedrest compared with a 2 month followup retest. However, a test of associational fluency and a test to measure capacity to shift the function of an object and use it in a different way did not reveal performance changes. Rothstein and Kikoshima (1978) studied 45 to 55 yr old males exposed to 10 days of bedrest. Four different tasks, including item recognition, visual search, category recognition, and analogy recognition were used to measure various aspects of the subjects' cognitive processing abilities. Although no significant differences between experimental and control group performance were discovered, Rothstein and Kikoshima comment that this finding may have been due to methodological and procedural difficulties rather than the lack of genuine performance changes.
Current data concerning how bedrest (and assumedly the space environment) affects performance have yielded either negative or inconsistent results. Given the significant biological alterations that occur during bedrest, it is difficult to imagine that performance would not be negatively affected in some way. There is considerable evidence that subjects experiencing bedrest do not find it a particularly pleasant condition. In fact, just the anticipation of starting the process is sufficient to increase depression, anxiety, and hostility. Such effects have also been noted throughout the period of recumbancy ( Ryback et al., 1971 a,1971 b).
 There appears to be a number of reasons why many bedrest studies fail to demonstrate any substantial change in performance. These include the length of the simulation, variability of results, and the identification and development of appropriate testing instruments. In all cases of bedrest simulation, the period of recumbency has been brief (at least in terms of the months and even years that future space missions may entail). We might speculate that a longer period of accumulated stress and biomedical alteration would be necessary before marked performance changes would be evident for all subjects during bedrest. However, researchers at Ames Research Center (personal communication, Charles Winget, August 1983) have noted that performance decrements are most noticeable during the first few days of recumbency, at least for studies up to 21 days in length. It remains to be determined whether more pronounced deterioration would occur over very long duration simulations.
High levels of inter and intra individual variability appear to be other factors that substantially reduce the chances of observing statistically significant group differences in bedrest studies. Certain individuals are more susceptible than others to performance decrements associated with bedrest. One factor contributing to both inter and intra individual variability could be the level of personal motivation. During an otherwise monotonous period of inactivity, performance tasks may be viewed as a welcome challenge and relief to the prevailing boredom. Increased effort derived from heightened motivation could overshadow otherwise expected performance decrements.
The development of appropriate test measures appears to be another stumbling block. Many tasks shown to be effective assessors of decremental performance under other adverse conditions cannot be effectively modified for use by subjects confined to a horizontal position. Further, because of the expense involved in bedrest studies, it is not always possible to have subjects available for lengthy prebedrest performance task training. Performance tasks used during recumbency usually must be fairly simple and quickly learned. This requirement excludes the use of sensitive but complex tasks that require extensive pretraining. If bedrest studies are to enhance our understanding of the behavioral as well as the physiological aspects of weightlessness, methodological and procedural issues must first be addressed .
The possible use of more frequent performance samplings, of additional performance tests to evaluate different levels of  performance (i.e., psychomotor, cognitive, perceptual, etc.), and perhaps bedrest regimens of longer durations sec avenues to be explored. Further, elucidation of the individual characteristics influencing performance changes might be obtained by concurrent psychological testing and EEG measurements. Concurrent testing could help evaluate the contributions of subject mood, motivation, sleep quality fatigue, anxiety, and general well being to performance in simulated weightlessness.
Resistance to Deconditioning
Although we cannot, at present, draw conclusions regarding how physiological deconditioning affects performance, there is certainly clear biomedical evidence that deconditioning can be dangerous to the safety and survival of the astronaut, if measures are not taken to limit or reverse the deconditioning process. The successful completion of two 6 month duration missions within an 18 month period by a Soviet cosmonaut (Gazenko, Genin, and Yegorov, 1981) does allay many of the fears for future missions. However, the capacity of different groups of humans to resist pressures will continue to be an area of obvious concern.
Traditionally, our approach to reducing physiological deconditioning in space has been to select men in top physical condition and maintain this condition through exercise Rigorous preflight and In flight conditioning programs have been maintained under the assumption that the better the astronaut's physical condition, the greater is his overall resistance to the stresses of spaceflight. In flight exercise does appear valuable in reducing muscle deconditioning. The comprehensive exercise program used during Skylab missions was effective in preventing loss of weight, maintaining leg strength and leg volume, and maintaining he integrity of muscle systems in general (Thornton and Rummel, 1977). However, in flight exercise by no means offers complete protection. Cosmonauts Berezovoi and Lebedev returned from their recent 211 day flight aboard Salyut 7 in obviously debilitated condition (Toufexis, 1983). Although they had exercised daily, their muscles were so flabby that they were barely able to walk for a week, and for several weeks afterwards required intensive rehabilitation.
Although in flight exercise has been shown to benefit external muscles, the benefits to other physiological systems must be questioned The Skylab exercise program did not deter decalcification or related problems of the skeletal system. Also, its usefulness in  preventing cardiac deconditioning and anomalies is suspect (Miller, Johnson, and Lamb, 1965). These data certainly suggest the need to reevaluate the role and value of in flight exercise.
Many studies suggest that there may be little advantage to rigorous pre flight exercise for well conditioned individuals. For example, when athletes (male subjects, ages 20 to 34 yr, who regularly exercised in endurance sports) and nonathletes were exposed to +Gz forces on a centrifuge, no significant differences on measures of acceleration tolerance were found between groups (Klein, Bruner, Jovy, Vogt, and Wegmann, 1969). Again, during a 20-min head up 90° vertical tilt test, no significant differences between groups with respect to orthostatic tolerance was found (Klein, Backhausen, Bruner, Eichhorn, Jovy, Schotte, Vogt, and Wegmann, 1968). Other investigators (Luft, Myhre, Leoppky, and Venters, 1976) have extended these studies and have shown that athletes actually have reduced orthostatic tolerance compared with nonathletes. During lower body negative pressure (LBNP) tests, aerobic work capacity was significantly reduced for both groups compared with baseline levels. However, although nonathletes demonstrated a slightly lower absolute decrement in capacity during LBNP testing, the athletic subjects showed a much larger relative loss in aerobic work capacity (almost 50%). Luft et al. also found that athletes show a greater tendency than nonathletes to accumulate fluid in the legs during LBNP.
Athletes also appear to be more susceptible to the effects of altitude than nonathletes. Rimpler (1970) found that the aerobic work capacity of athletes compared with nonathletes declined at a significantly faster rate during simulated altitude increments. Accordingly, athletic subjects seem to be more adversely affected by a reduction in environmental partial oxygen pressure than their nonathletic counterparts.
Athletic and nonathletic populations compared during water immersion show similar differential tolerance (Stegemann, Meier, Shipka, Hartlieb, Hemmer, and Tiebes, 1975). Athletes showed a significantly greater relative reduction in aerobic work capacity following 6-hr immersion than did nonathletes. Furthermore, all athlete subjects fainted during a 10-min vertical tilt test following immersion, whereas none of the nonathletes experienced this problem. One other aspect of Stegemann et al.'s experiment is intriguing. Intermittent swimming exercise during immersion was found to improve circulatory responses during subsequent tilt table tests.  However, this aid was more effective for nonathletes than for athletes.
Data obtained in flight appear to support the findings so far discussed. For example, using the aerobic capacity of athletic and nonathletic populations for comparison, Klein, Wegmann, and Kuklinski (1977) classified the preflight physical fitness status of the Skylab 4 Scientist Pilot and Pilot as "good" to "excellent." The Commander was classified as "fair" in fitness. During the mission, the two crewmen in better physical condition clearly demonstrated poorer responses to provocative gravitational stress than did the Commander. This effect was reflected in a more pronounced increase in heart rate and calf volume, and by a greater reduction of pulse pressure during LBNP (Johnson, Hoffler, Nicogossian, Bergman, and Jackson, 1974). Also during postflight LBNP stress, the Scientist Pilot and the Pilot showed a higher degree of orthostatic intolerance than the Commander, even though they exercised in flight more than the Com mender.
From the data available so far, it appears that there is a need to reevaluate the role of physical fitness in the astronaut program. This is true particularly in light of the inclusion of mission and payload specialists whose physical capabilities may differ from those of the traditional astronaut pilot (NASA, 1977a, 1977b, 1977c). We need to better determine the degree of physical conditioning most suitable for astronaut crews (and their respective specialist members) as well as the type, amount, and scheduling of exercise to be used.
Age- Several studies have found that older, less physically active individuals adapt better to certain stresses of 0 g than their younger, more athletic counterparts For example, Hull, Wolthuis, Gillingham, and Triebwasser (1978) found that +Gz acceleration tolerance was slightly greater among healthy male subjects between 40 to 55 yr old than among comparably tested younger subjects. Sandler, Goldwater, Rositano, Sawin, and Booher (1979) found comparable +Gz acceleration tolerance results for individuals (ages 46 to 55) following bedrest. Similarly, Convertino, Olsen, Goldwater, and Sandler (1979) found that reductions in functional working capacity following bedrest as measured by cardiorespiratory responses was less for older (age 50 ±1 yr) than younger (age 21 ± 2 yr) individuals. However, there was a greater increase in the maximal heart rate observed after bedrest among the older men.
 Older subjects also appear to withstand orthostatic stress better than their younger counterparts. Goldwater, Montgomery, Hoffler, Sandler, and Popp (1979) found that men aged 46-55, when compared with men aged 35-44, were more resistant to the effects of LBNP following bedrest. Older subjects demonstrated greater preservation of leg blood flow, less leg and pelvic blood pooling, and smaller decreases in end diastolic volume and stroke volume.
These studies, combined with those examining the adaptability of various athletic populations, suggest the intriguing possibility that normally active older subjects may have greater tolerance to weightlessness deconditioning, at Ieast cardiovascular deconditioning, than the more highly conditioned astronauts we have selected in the past If so, the mechanisms which confer protection with aging need to be understood. One possibility is that a body that is not "well tuned" does not discriminate as well as a conditioned body and therefore does not respond as markedly to environmental changes. An important question is whether older subjects may be more or less tolerant of 0-g stresses with respect to physiological systems other than the cardiovascular system. There is evidence from animal research suggesting that older individuals may be at a disadvantage in tolerating weightlessness as it affects the skeletal system. Novikov and lI'in (1981) have shown that among rats of various ages subjected to immobilization simulating null gravity effects, there is an age-dependent variation in the relative rates of bone formation and resorption. Older animals show the highest net rate of bone loss during immobilization. It is important that such effects be investigated in humans along with a more comprehensive evaluation of age-dependent biomedical changes in other systems as affected by spaceflight conditions.
In discussing the effects of aging on the adaptability of individuals exposed to simulated weightlessness stressors, we might do well to consider also the other end of the age scale. As we anticipate an expanded age range of crews and especially of passengers in space, we will need to know what effects weightlessness will have on younger populations. Since ethical considerations severely restrict the inclusion of infants, children, and adolescents in experimental investigations, other methods of assessing the likely impact of weightlessness on these populations need to be identified.
Gender- Current space related research with subject populations radically different from those historically considered appropriate for space travel leads to a discussion of the biomedical  implications of women in space. During the early 1960s, the L Lovelace Clinic in Albuquerque, New Mexico, conducted tests to determine the qualifications of women for spaceflight (Lovelace, Schwichtenberg , Luft, and Secrest, 1962). These tests showed women to he as suitable as men for space travel, especially so when one talcs into consideration the fact that physical strength is much less important in space than on Earth. Further, women may be more suitable for space missions than men in some ways. Women generally weigh less and therefore consume less food and oxygen than men (Boyle, 1978). Also, it has been reported that women are more radiation resistant than men (Rowes, 1982).
Recently, in light of the decision to include women crew members in the Space Shuttle, research has been reinitiated to further extend our understanding, of female responses to the space environment and particularly to weightlessness. This renewed investigation has come in the form of bedrest studies involving comprehensive analyses of female responses to hypokinesis and related stressors.
These studies, as reviewed by Sandler and Winter (1979), have shown that women do demonstrate some significantly different responses to bedrest than men. Tests during LBNP have demonstrated greater change in cardiovascular dynamics among women as evidenced by a higher rate of fainting from lowered blood supply to the brain than observed among men. Significant sex differences exist also in postsimulation centrifugation tolerance. Mean tolerance losses among women exposed to bedrest is about 50% greater than among men, although the range of values is quite similar across sexes. However, there is also evidence that women may recover faster from centrifugation than men.
In most other areas investigated, only minor differences appear in the response of men and women to hypokinesis. Although the absolute physical work capacity of women is normally much lower than that of men, relative losses due to deconditioning from bedrest are about the same for both sexes. Also, no significant differences in biochemical changes between men and women exposed to hypokinesis have been demonstrated. Finally, the rhythmicity of various internally regulated biological functions appears to be only superficially different between the sexes. Some phase differences in the peak and trough values of hormonal and metabolic circadian rhythms do exist, but they are of minor consequence.
 Although the results of studies investigating gender differences in response to simulated space conditions are still sparse and tentative, the overall conclusion is that men and women differ little in their ability to adapt to the biomedical stresses of space travel. Further, Sandler has indicated that women may be superior to men at withstanding the combined stresses of space (Rowes, 1982). According to a 5-yr study conducted at Ames Research Center, 27 women studied did a better job than their male counterparts in adapting to the physical and psychological challenges of bedrest and to the strenuous biomedical testing used to assess the effects of bed rest.
Given the lack of available in flight data on women in space, many research questions remain regarding the biomedical response of females to space travel. For example, the question of the relationship between monthly cycles and performance is one topic that has been extensively researched in mundane environments (Redgrove, 1971). Sandler and Winter (1979) found no significant physiological changes during menses as a result of bedrest. Nonetheless, it is known that women experience shifts in blood volume and fluid balance as a result of their monthly period. How these shifts interact with shifts in blood volume and fluid balance produced by weightlessness is at present unknown. It is hoped that data from Soviet flights and data resulting from the inclusion of women in the American space program will provide further insight to the various aspects of female adaptation to space.
Several alternatives have been explored as possible countermeasures to the physiological deconditioning that occurs in space. Exercise and selection procedures are options discussed in an earlier section of this chapter. Diet and nutritional supplements (Ushakov, Myasnikov, Shestkov, Agureev, Belakovsky, and Rumyantseva, 1978) have also been suggested. Two other alternatives, pharmacological manipulations and artificial gravity regimes, are discussed below.
Drugs- The possibility of using drugs to treat biomedical alterations produced during spaceflight has been discussed for some time (Parin, Vinogradov, and Razumeev, 1969). Soviet scientists have employed a wide range of pharmaceuticals to treat cardiovascular deconditioning in space (Shashkov and Yegorov, 1979) and to normalize water sodium metabolism. Parin et al. (1969) and Parin, Kosmalinskly, and Dushkov (1970) have discussed the use of  pharmaceuticals in the treatment of various cardiovascular changes produced by weightlessness. They have also considered the possible pharmaceutical treatment of metabolic anomalies associated with weightlessness, radiation dangers inherent in space, and biomedical alterations associated with launch and landing accelerations. More recently, investigators have considered the use of certain drugs to compensate for bone demineralization problems in weightlessness. For example, certain drugs show some promise as countermeasures for the effects of bedrest on the skeleton and may be effective for spaceflight (Nicogossian and Parker, 1982; Dietlein and Johnston, 1981).
Although the possibility of using drugs to treat spaceflight physiological alterations offers promise, there are some important research questions which have yet to be addressed adequately. One general question concerns whether or not a given drug will affect the body in space in a manner similar to its action on Earth. Due to changes in blood pressure, fluid volume, and metabolism produced by weightlessness, the time course of drug action and its overall effect may be altered significantly. Since major biomedical alterations occur in weightlessness, one cannot assume that the particular system to be treated will react to the drug in the same way as on Earth.
No major research has been conducted in space to examine these possibilities. However, we can gain some insight as to possible changes in space by examining how drug action is altered during exposure to other types of extreme environments. Aviation studies of drug action under varying altitude conditions demonstrate that this type of environment does produce significant changes in drug action effect. Drug toxicities are known to change, often increasing, for various drugs ingested under high altitude conditions (Margolis, Bernheim, and Hurteau, 1951; Nedzel, 1955; Baumel, Robinson, and Blatt, 1967). High altitude may also potentiate drug action at nontoxic levels. For instance, Sparvieri (1960) reported that increased altitude potentiated the tranquilizing action of chlorpromazine, and altitude has been found to increase the morphine pain threshold (Truchaud, 1966). We also know that drug action can be altered in high altitudes due to metabolic changes. For example, altitude increases metabolism of some drugs, but decreases metabolism of other drugs (as reported by Medina, 1970).
It is not entirely clear which factors in high altitudes produce these changes Probably, it is a combination of (1) reduced oxygen  (although many studies have found comparable results with and without ground equivalent oxygen), (2) pressure changes, and (3) nonspecific stress factors. Depending on the characteristics of a particular mission, spaceflight may or may not mimic these effects. However, the results from high altitude studies do indicate that environmental changes which alter normal ground based physiological functioning can significantly influence the course of drug action. This implies that drug action under spaceflight conditions could be different from Earth. Fortunately, a slight intensification or reduction in the effect of most drugs usually does not produce great problems. However, the importance of such an effect depends upon the situation and the medication. Small but adverse changes in biomedical responses to potentially toxic chemicals could prove problematic during critical mission phases. As a basic research question, it seems important that we consider the interaction of drugs and physiology under conditions of weightlessness.
A second question involving the use of drugs in space concerns their interaction with biological rhythms. Recently, chronobiology, or the study of biological rhythms, has emerged as a distinct field of research (Brown and Greaber, 1982). A related field, chronopharmocology, or the study of drugs administered at different times of the day, is also gaining interest. It is known, for instance, that an oral dose of antihistamine given at 7 p.m. will last 6 to 8 hr, whereas the same dose given at 7 a.m. will last 15 to 17 hr. On the other hand, digitalis (a heart medication) has twice the effect when given at night as when administered during the day. One implication of these findings is that drugs can be given in effectively lower doses if properly timed (NASA Activities, vol. 13, no. 10, 1982, p. 10). Extending these considerations to the space environment raises questions of the interaction effects of weightlessness, biological rhythms, and the administration of medication, and the possible behavioral implications of such interactions.
A third question concerns how to administer drugs in space A new method has recently been developed which has the potential of offering greater control over absorption, and therefore over the effects of medication (Hackler, 1982). One device, called a Transderm V System, consists of a patch worn just behind the ear. Whatever chemical it contains is absorbed directly into the bloodstream through the skin. Medication can be dispensed at a continuous and adjustable r ate for up to 3 clays. Such a system has distinct potential advantages. Since orally administered chemicals must pass through the gastrointestinal tract where much of the dosage is lost,  large concentrations must be taken in order to ensure that a therapeutic amount reaches the bloodstream . Gradual absorption directly into the bloodstream could permit the use of much lower dosages minimizing the risk of side effects . Another advantage is that administrations do not have to be scheduled info an already hectic workday.
The Transderm V System was employed recently by astronauts aboard c. the S Space Shuttle Columbia . Although the system a appears to have advantages over oral administrations of prophylactic drugs, it is not clear that the transdermal system is any more effective than oral ingestion. Wurster, Burchard, and von Restorff (1981) found that the effect of an anti motion sickness medication administered transdermally could not be distinguished from that of a placebo; Homick, Degioanni, Reschke, Leach, and Kohl (1982) report similar findings Both reports note great inter and intra individual variations in drug action, which hindered statistical analyses. Further tests arc needed to detail the effectiveness of routine and/or long term use of such a system for spaceflight.
Artificial gravity One possibility that has been suggested as a countermeasure to the effects of weightlessness is the use of artificially produced gravity aboard spacecraft. Artificial gravity could be accomplished either through rotation of the entire vehicle or by the inclusion of an on board centrifuge.
Rotation of the vehicle has a high apparent validity, and to the degree that it can be developed to approximate a normal linear gravitational environment, would produce the more comfortable living arrangement for~ long duration spacecrews. Unfortunately, a rather large vehicle is necessary to produce axial rotation simulating Earthtype gravitational conditions. A short radius craft gives a poor approximation to linear gravity and may yield a number of undesirable phenomena, including locomotor difficulty, spatial disorientation, and motion sickness. Because of the design constraints in producing 1 g artificial gravity through vehicle rotation, it is important to deter mine how little a g load is sufficient to maintain adequate protection against deconditioning.
An important issue regarding the use of any rotational vehicle artificial gravity system is how adaptation to such a system would proceed. Earth based rotational studies using vertical axis rotation have shown that adaptation can occur within about 24 hr for angular velocities at Ieast as great as 6.0 rpm (Graybiel, Guedry, Johnson,  and Kennedy, 1961; Newsom, Brady, and Goble, 1965; Newsom, Brady, Shafer, and French, 1966). However, the rotation in a weightless spacecraft is significantly different from that in an Earth based room (Guedry, 1965). In a rotating spacecraft, pitch and roll head movements, angular limb movements, and horizontal translation will have dramatically different effects from those found on Earth, depending upon the crewmembers' orientation. Adaptation to rotation in space may therefore occur at a slower rate than in Earthbased rotation studies.
An alternate approach to the negation of 0-g effects through artificial gravity is the use of an on board centrifuge. Much of the centrifuge work has been done in connection with the development of the Manned Orbiting Research Laboratory (Singer, 1968; Stapp, 1969). Researchers have shown that as few as four 7.5-min exposures to +1.7 Gz at the heart largely prevents orthostatic intolerance (W. White, 1965b; W. White, Nyberg, White, Grimes, and Finney, 1965; P. White, Nyberg, Finney, and White, 1966). However, adverse bedrest induced changes in heart rate and blood pressure were not improved.
The most recent attempts to test the centrifuge system in space produced some promising resuIts. In the Cosmos 936 flight of 1977, rats were exposed to centrifugation during 18.5 days of weightless spaceflight. Flight results showed that the lifespan of centrifuged animals was significantly greater than that of noncentrifuged control animals (Leon, Serova, and Landaw, 1978). Hemolysis increased three fold in non centrifuged flight animals, but was significantly less in those subjects exposed to centrifugation.
The bone system also seems to be positively affected by centrifugation in space (Horton, Turner, and Baylink, 1979). Bone mechanical properties including torque, stiffness, and energy were shown to significantly decrease among noncentrifuged flight animals, but were normal among flight subjects exposed to centrifugation. Also, although centrifugation did not correct loss of bone formation during flight, it did speed up recovery following return to Earth. Furthermore, centrifugation helped to prevent changes in calcium and phosphorus content in rat long bones (Gazenko, lI'in, Genin, Kotovskaya, Korol'kov, Tigranyan, and Portugalov, 1980) and helped to prevent osteoporosis (Stupakov, 1981).
Although these results are based on a small sample of subjects, they are encouraging and illustrate the need for further understanding of the effects of on board centrifuge systems. It remains to be  determined whether engineering innovations and the use of artificial gravity systems will prove more advantageous than alternative physiological countermeasures such as drugs, diet, exercise, etc. in countering the deconditioning effects of weightlessness.
1 Calcium loss, however, appears to occur at a faster rate in space than during bedrest simulations.