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PubMed1992

Biochemical and hematologic changes after short-term space flight.

Clinical laboratory data from blood samples obtained from astronauts before and after 28 flights (average duration = 6 days) of the Space Shuttle were analyzed by the paired t-test and the Wilcoxon signed-rank test and compared with data from the Skylab flights (duration approximately 28, 59, and 84 days). Angiotensin I and aldosterone were elevated immediately after short-term space flights, but the response of angiotensin I was delayed after Skylab flights. Serum calcium was not elevated after Shuttle flights, but magnesium and uric acid decreased after both Shuttle and Skylab. Creatine phosphokinase in serum was reduced after Shuttle but not Skylab flights, probably because exercises to prevent deconditioning were not performed on the Shuttle. Total cholesterol was unchanged after Shuttle flights, but low density lipoprotein cholesterol increased and high density lipoprotein cholesterol decreased. The concentration of red blood cells was elevated after Shuttle flights and reduced after Skylab flights. Reticulocyte count was decreased after both short- and long-term flights, indicating that a reduction in red blood cell mass is probably more closely related to suppression of red cell production than to an increase in destruction of erythrocytes. Serum ferritin and number of platelets were also elevated after Shuttle flights. In determining the reasons for postflight differences between the shorter and longer flights, it is important to consider not only duration but also countermeasures, differences between spacecraft, and procedures for landing and egress.

Adaptation, Physiological↗

PubMed1994

Exercise against lower body negative pressure as a countermeasure for cardiovascular and musculoskeletal deconditioning.

Exposure to lower body negative pressure (LBNP) with oral salt and water ingestion has been tested by astronauts as a countermeasure to prevent postflight orthostatic intolerance. Exercise is another countermeasure that astronauts commonly use during spaceflight to maintain musculoskeletal strength. We hypothesize that a novel combination of exercise and simultaneous exposure to lower body negative pressure during spaceflight will produce Earth-like musculoskeletal loads as well as cardiovascular stimuli to maintain adaptation to Earth's gravity. Results from recent studies indicate that leg exercise within a LBNP chamber against the suction force of 100 mmHg LBNP in horizontal-supine posture produces an equivalent, if not greater exercise stress compared to similar leg exercise in upright posture (without LBNP) against Earth's gravity. Therefore, the concept of LBNP combined with exercise may prove to be a low cost and low mass technique to stress the cardiovascular and the musculoskeletal systems simultaneously.

Adult↗

PubMed1994

The effect of dDAVP with saline loading on fluid balance during LBNP and standing after 24-hr head-down bedrest.

Shuttle astronauts currently drink approximately a quart of water with eight salt tablets before reentry to restore lost body fluid and thereby reduce the likelihood of cardiovascular instability and syncope during reentry and after landing. However, the saline loading countermeasure is not entirely effective in restoring orthostatic tolerance to preflight levels. We tested the hypothesis that the effectiveness of this countermeasure could be improved with the use of a vasopressin analog, 1-deamino-8-D-arginine vasopressin (dDAVP). The rationale for this approach is that reducing urine formation with exogenous vasopressin should increase the magnitude and duration of the vascular volume expansion produced by the saline load, and in so doing improve orthostatic tolerance during reentry and postflight.

Adult↗

PubMed1991

Carotid-cardiac baroreflex: relation with orthostatic hypotension following simulated microgravity and implications for development of countermeasures.

In a series of studies, we have examined the effects of exposure to simulated microgravity, varying states of vascular volume, and acute exercise on the function of the carotid-cardiac baroreflex in man. In the first study, exposure to simulated microgravity (6 degrees headdown bedrest) reduced the sensitivity and buffer capacity of the vagal baroreceptor-cardiac reflex mechanisms and this impaired baroreflex function was associated with orthostatic hypotension. Since the reduction in plasma volume during BR was not correlated with impaired baroreflex function, a second study was conducted which demonstrated that the carotid-cardiac baroreflex response was not affected by either acute hypovolemia or hypervolemia. These results suggest that acute fluid replacement prior to reentry may not reverse impaired baroreflex function associated with postflight hypotension. In a third study, we demonstrated that one bout of maximal exercise increased baroreflex sensitivity and buffer capacity through 24 h post-exercise. These baroreflex changes were opposite to those observed following BR. Taken together, these data suggest that the contributions of reduced blood volume and impaired carotid-cardiac baroreflex function to orthostatic hypotension following exposure to microgravity are probably separate and additive; maximal exercise in addition to fluid replacement may provide an acute effective countermeasure against postflight hypotension.

Adult↗

PubMed1996

Regulation of body fluid compartments during short-term spaceflight.

The fluid and electrolyte regulation experiment with seven subjects was designed to describe body fluid, renal, and fluid regulatory hormone responses during the Spacelab Life Sciences-1 (9 days) and -2 (14 days) missions. Total body water did not change significantly. Plasma volume (PV; P < 0.05) and extracellular fluid volume (ECFV; P < 0.10) decreased 21 h after launch, remaining below preflight levels until after landing. Fluid intake decreased during weightlessness, and glomerular filtration rate (GFR) increased in the first 2 days and on day 8 (P < 0.05). Urinary antidiuretic hormone (ADH) excretion increased (P < 0.05) and fluid excretion decreased early in flight (P < 0.10). Plasma renin activity (PRA; P < 0.10) and aldosterone (P < 0.05) decreased in the first few hours after launch; PRA increased 1 wk later (P < 0.05). During flight, plasma atrial natriuretic peptide concentrations were consistently lower than preflight means, and urinary cortisol excretion was usually greater than preflight levels. Acceleration at launch and landing probably caused increases in ADH and cortisol excretion, and a shift of fluid from the extracellular to the intracellular compartment would account for reductions in ECFV. Increased permeability of capillary membranes may be the most important mechanism causing spaceflight-induced PV reduction, which is probably maintained by increased GFR and other mechanisms. If the Gauer-Henry reflex operates during spaceflight, it must be completed within the first 21 h of flight and be succeeded by establishment of a reduced PV set point.

Adult↗

PubMed1992

Countermeasures against space flight related bone loss.

This paper reviews human data concerning bone loss and attempted countermeasures during spaceflight and bed rest, a commonly employed technique to simulate the effects of weightlessness on the musculoskeletal system.

Bed Rest↗

PubMed1991

Mathematical modeling of acute and chronic cardiovascular changes during Extended Duration Orbiter (EDO) flights.

The Extended Duration Orbiter (EDO) program aims to extend the capability of the Shuttle orbiter beyond its current 7-10 day limit on mission duration. This goal is to be accomplished in steps, partly due to our limited knowledge of the physiological changes resulting from long-term exposure to weightlessness and their likely influence on critical mission operations involved in EDO flights. Answers to questions related to physiologic adaptation to weightlessness are being actively sought at the present time to help implement the EDO program. In the cardiovascular area, the loss of orthostatic tolerance is a medical concern because of its potential adverse effects on crew performance and safety during reentry and following return to earth. Flight and ground-based physiologic studies are being planned to understand the mechanism and time course of spaceflight-induced orthostatic intolerance and to develop effective countermeasures for improving post-flight cardiovascular performance. Where feasible, these studies are aided by theoretical analyses using mathematical modeling and computer simulation of physiological systems. This paper is concerned with the application of proven models of circulatory and cardiovascular systems in the analysis of chronic cardiovascular changes under weightless conditions.

Cardiovascular Deconditioning↗

PubMed1993

Simulation of the fluid retention effects of a vasopressin analog using the Guyton model of circulation.

Fluid-loading (FL) consisting of water and salt tablets equivalent of 32 oz of isotonic saline is a countermeasure currently in use by NASA to improve the orthostatic tolerance of astronauts during Shuttle reentry. However, the effectiveness of this countermeasure has been observed to decrease with the duration of space flight. Possible ways to improve fluid retention and thus the effectiveness of FL include use of analogs of vasopressin such as lypressin (LVP). This study used a computer simulation approach to analyze the potential benefits on fluid retention with LVP administered before FL.

Blood Volume↗

PubMed1996

Effect of standing or walking on physiological changes induced by head down bed rest: implications for spaceflight.

BACKGROUND/HYPOTHESIS: To simulate exposure to microgravity and to determine the effectiveness of intermittent exposure to passive and active +1 Gz force (head-to-foot) in preventing head-down bed rest (HDBR) deconditioning, 4 d of 6 degrees HDBR were used. METHODS: Volunteers were 9 males, 30-50 yr, who performed periodic standing or controlled walking for 2 or 4 h.d-1 in 15-min bouts, one bout per hour, or remained in a continuous HDBR control condition (0 Gz). RESULTS: Standing 4 h (S4) completely prevented, and standing 2 h (S2) partially prevented, decreases in post-HDBR orthostatic tolerance (survival rates with 30 min of upright tilt at 60 degrees). Walking, both 2 h (W2) and 4 h (W4), and S4 attenuated decreases in peak oxygen uptake compared to 0 Gz. Compared to 0 Gz, both S4 and W4 attenuated plasma volume loss during HDBR. Urinary Ca2+ excretion increased over time with HDBR; the quadratic trend for urinary Ca2+, however, was attenuated with W2 and W4. CONCLUSIONS: We concluded that various physiological systems benefit differentially from passive +1 Gz or activity in +1 Gz and, in addition to the duration of the stimulus, the number of exposures to postural stimuli may be an important moderating factor.

Adult↗

PubMed1991

Neuromuscular aspects in development of exercise countermeasures.

Based on the results generated from experiments conducted by our investigators, it is clear that prolonged exposure to microgravity environments can induce ultrastructural abnormalities and atrophy of muscle and impair muscle function, especially upon return to terrestrial gravity. It is also apparent that ground-base models can be effectively used to study these changes. This provides a less expensive and more controlled laboratory condition in order to conduct experiments. The use of animal models must be more closely examined. In the case of muscle adaptations to microgravity, the data from flight experiments which have used rodents might suggest the use of exercise with characteristics contrary to those which would be most appropriate to defend against atrophy and dysfunction in human muscle. Although many spaceflight experiments may be limited to the use of animal models, the results of the studies reviewed in this paper emphasize the importance of using human models in order to provide the most accurate interpretation of data for the development of exercise countermeasures for spaceflight. If maintenance of muscle structure, size and function is perceived as operationally necessary, the results from the studies conducted by our investigators indicate that the use of more resistive exercise must be given greater consideration as part of the development of future exercise countermeasure programs for spaceflight. The advantages of incorporating resistive exercise with a strong emphasis on the use of eccentric muscle actions in addition to concentric actions may prove most effective as a countermeasure against the muscle atrophy and dysfunction caused by long-duration exposure to microgravity environments.

Adult↗

PubMed1991

Development of lower body negative pressure as a countermeasure for orthostatic intolerance.

Exposure to prolonged (1-4 hr) lower body negative pressure (LBNP) is a countermeasure against postflight orthostatic intolerance which is used in the Soviet space program and planned for use in the American space program. LBNP in combination with fluid-loading is believed to act by promoting a transient positive fluid balance resulting in an increase in vascular, as well as extravascular fluid. Inflight LBNP also may provide beneficial orthostatic effects by restoring baroreceptor reflex functions and/or lower body venous compliance. Current research efforts at the Johnson Space Center are directed towards increasing the effectiveness and efficiency of the LBNP and saline countermeasure. A promising avenue may involve combining pharmacologic agents, such as inhaled anti-diuretic hormone, or mineralocorticoids, with mechanical stimuli such as LBNP.

Humans↗

PubMed1997

Regulation of body fluid volume and electrolyte concentrations in spaceflight.

Despite a number of difficulties in performing experiments during weightlessness, a great deal of information has been obtained concerning the effects of spaceflight on the regulation of body fluid and electrolytes. Many paradoxes and questions remain, however. Although body mass, extracellular fluid volume, and plasma volume are reduced during spaceflight and remain so at landing, the changes in total body water are comparatively small. Serum or plasma sodium and osmolality have generally been unchanged or reduced during the spaceflight, and fluid intake is substantially reduced, especially during the first of flight. The diuresis that was predicted to be caused by weightlessness, has only rarely been observed as an increased urine volume. What has been well established by now, is the occurrence of a relative diuresis, where fluid intake decreases more than urine volume does. Urinary excretion of electrolytes has been variable during spaceflight, but retention of fluid and electrolytes at landing has been consistently observed. The glomerular filtration rate was significantly elevated during the SLS missions, and water and electrolyte loading tests have indicated that renal function is altered during readaptation to Earth's gravity. Endocrine control of fluid volumes and electrolyte concentrations may be altered during weightlessness, but levels of hormones in body fluids do not conform to predictions based on early hypotheses. Antidiuretic hormone is not suppressed, though its level is highly variable and its secretion may be affected by space motion sickness and environmental factors. Plasma renin activity and aldosterone are generally elevated at landing, consistent with sodium retention, but inflight levels have been variable. Salt intake may be an important factor influencing the levels of these hormones. The circadian rhythm of cortisol has undoubtedly contributed to its variability, and little is known yet about the influence of spaceflight on circadian rhythms. Atrial natriuretic peptide does not seem to play an important role in the control of natriuresis during spaceflight. Inflight activity of the sympathetic nervous system, assessed by measuring catecholamines and their metabolites and precursors in body fluids, generally seems to be no greater than on Earth, but this system is usually activated at landing. Collaborative experiments on the Mir and the International Space Station should provide more of the data needed from long-term flights, and perhaps help to resolve some of the discrepancies between U.S. and Russian data. The use of alternative methods that are easier to execute during spaceflight, such as collection of saliva instead of blood and urine, should permit more thorough study of circadian rhythms and rapid hormone changes in weightlessness. More investigations of dietary intake of fluid and electrolytes must be performed to understand regulatory processes. Additional hormones that may participate in these processes, such as other natriuretic hormones, should be determined during and after spaceflight. Alterations in body fluid volume and blood electrolyte concentrations during spaceflight have important consequences for readaptation to the 1-G environment. The current assessment of fluid and electrolyte status during weightlessness and at landing and our still incomplete understanding of the processes of adaptation to weightlessness and readaptation to Earth's gravity have resulted in the development of countermeasures that are only partly successful in reducing the postflight orthostatic intolerance experienced by astronauts and cosmonauts. More complete knowledge of these processes can be expected to produce countermeasures that are even more successful, as well as expand our comprehension of the range of adaptability of human physiologic processes.

Body Fluids↗

PubMed1993

Physiologic mechanisms effecting circulatory and body fluid losses in weightlessness as shown by mathematical modeling.

The mechanisms causing large body water losses in weightlessness are not clear. It has long been considered that a central volume expansion drives the physiologic adaptation to a reduced total blood volume, with normal blood composition eventually regained. However, inflight venous pressure measures suggest that central volume expansion in weightlessness may be very transient, or that considerable cardiovascular adaptation to fluid shifts occurs on the ground while astronauts wait in the semi-supine pre-launch position. If a central volume stimulus does not persist, other mechanisms must drive the adaptation of circulation to a reduced blood volume and account for body fluid losses. Recent results from the SLS-1 mission suggest that body fluid volumes do not simply decline to new equilibria but that they decrease to a low point, then undergo some recovery. Similar "under-shoots" of body fluid volumes have also been shown in computer simulations, providing confidence in the validity of the model. The purpose of this study was to examine the mechanisms which could explain the loss of body fluids in weightlessness and how a cardiovascular preadaptation countermeasure we previously tested ameliorated body fluid losses. It is assumed that the physiology of head down tilt (HDT) provides a reasonably accurate analog of weightless exposure.

Blood Viscosity↗

PubMed1991

Cardiovascular function in space flight.

Changes in orthostatic heart rate have been noted universally in Soviet and U.S. crewmembers post space flight. The magnitude of these changes appears to be influenced by mission duration, with increasing orthostatic intolerance for the first 7-10 days of flight and then a partial recovery in the orthostatic heart rate response. Fluid loading has been used as a countermeasure to this postflight orthostatic intolerance. Previous reports have documented the effectiveness of this technique, but it has also been noted that the effectiveness of volume expansion diminishes as flight duration exceeds one week. The response of carotid baroreceptor function was investigated utilizing a commercially available neck collar which could apply positive and negative pressure to effect receptor stimulation. Bedrest studies had validated the usefulness and validity of the device. In these studies it was shown that carotid baroreceptor function curves demonstrated less responsiveness to orthostatic stimulation than control individuals. Twelve Space Shuttle crewmembers were examined pre- and postflight from flights lasting from 4-5 days. Plots of baroreceptor function were constructed and plotted as change in R-R interval vs. carotid distending pressure (an orthostatic stimulus). Typical sigmoidal curves were obtained. Postflight the resting heart rate was higher (smaller R-R interval) and the range of R-R value and the slope of the carotid sigmoidal response were both depressed. These changes were not significant immediately postflight (L + O), but did become significant by the second day postflight (L + 2), and remained suppressed for several days thereafter. It is hypothesized that the early adaptation to space flight involves a central fluid shift during the initial days of flight, but subsequent alterations in neural controlling mechanisms (such as carotid baroreceptor function) contribute to orthostatic intolerance.

Adaptation, Physiological↗

PubMed1991

Orthostatic function during a stand test before and after head-up or head-down bedrest.

Astronauts may exhibit orthostatic dysfunction upon returning to 1 g after space flight. Understanding cardiovascular changes at 0 G will provide insights into the mechanisms of the loss of orthostatic tolerance, whether due to space flight or bedrest. Bedrest is one model used to produce cardiovascular changes that are associated with space flight. In the current study, young male adults were placed at -5 degrees, +10, +20, or +42 degrees bedrest (0, 1/6, 1/3, and 2/3g, respectively) for 6 hours on 4 different days. This was preceded and followed by a stand test: 5 minutes in the supine position, and then 5 minutes in the standing position, with the feet 9 inches apart and 6 inches from the wall. Cardiovascular values were measured at 1-minute intervals. Systolic and diastolic pressures were measured using an automated blood pressure device; mean arterial pressure (MAP; mm Hg) was calculated. Heart rate (bpm) and cardiac parameters were measured with a thoracic impedance device. Minute 3, 4, and 5 values were used to determine whether there were time or angle effects. Of six subjects, one reported nausea upon 3 minutes of standing after 6 hours of bedrest at -5 degrees. The same subject was lightheaded in the first minute of standing after 6 hours of bedrest at +10 degrees. Mean heart rate pre-bedrest in the supine position was 63 and increased by 24 bpm on standing. Heart rate post-bedrest in the supine position was 65 and increased by 35 bpm on standing; standing heart rate increased 11 bpm after -5 degrees bedrest. The increases after +10 degrees, +20 degrees, and +42 degrees tilts were 4, 3, and 4 bpm, respectively. Changes in the mean arterial blood pressure were minimal. Results from the stand test pre- and post- 6 hours of bedrest at -5 degrees but not at +10 degrees, +20 degrees, or +42 degrees are similar to those after space flight.

Adult↗

PubMed1991

Metabolic changes observed in astronauts.

Study of metabolic alterations that occur during space flight can provide insight into mechanisms of physiologic regulation. Results of medical experiments with astronauts reveal rapid loss of volume (2 L) from the legs and a transient early increase in left ventricular volume index. These findings indicate that, during space flight, fluid is redistributed from the legs toward the head. In about 2 days, total body water decreases 2 to 3%. Increased levels of plasma renin activity and antidiuretic hormone while blood sodium and plasma volume are reduced suggest that space flight-associated factors are influencing the regulatory systems. In addition to fluid and electrolyte loss. Skylab astronauts lost an estimated 0.3 kg of protein. Endocrine factors, including increased cortisol and thyroxine and decreased insulin, are favorable for protein catabolism. The body appears to adapt to weightlessness at some physiologic cost. Readaptation to Earth's gravity at landing becomes another physiologic challenge.

Humans↗

PubMed1991

New pharmacologic approaches to the prevention of space/motion sickness.

Fundamental approaches in selection of new agents for evaluation in prevention of space/motion sickness (SMS) are reviewed. The discussion centers on drugs under investigation at the Johnson Space Center. Methodology that employs the rotating chair for measuring SMS symptomatology and susceptibility is described. The most obvious approach to the development of new agents relies on selection of agents from drug classes that possess pharmacologic properties of established anti-motion sickness agents. A second approach selects drugs that are used to prevent emesis caused by means other than exposure to motion. The third approach relies on basic research that characterizes individual differences in susceptibility. The hypothesis is: detection of individual differences leads to identification of specific drugs, which target physiologic systems that show individual differences. These physiologic systems are targets for therapy and may play a role in the etiology of SMS. Two drugs that reduce susceptibility to SMS include dexamethasone and d(CH2)5Tyr(Me)AVP, a vasopressin (AVP)V1 antagonist. The latter peptide has demonstrated complete blockade of emesis and other significant symptoms in squirrel monkeys. These studies were predicated on observations that subjects who were more resistant to SMS had higher plasma AVP after severe nausea than subjects with lower resistances. Investigations are underway to test a 0.5-mg intravenous dose in humans. Kappa opioid agonists inhibit AVP release and offer new therapeutic possibilities and advantages over AVP peptides. This review details the experimental data collected on AVP and adrenocorticotropin. The literature supports interrelated roles for AVP and opioid peptides in SMS. Experimental testing of kappa agonists is warranted because specific opioid agonists act at neuroanatomical sites causing nausea and vomiting. It is argued opioid receptors in the chemoreceptor trigger zone and vomiting center stimulate and inhibit the emetic response, respectively. The evidence suggests kappa and/or mu receptors at VC are involved in inhibition of emesis, whereas delta opioid receptors at CTZ are involved in stimulation of emesis.

Drug Therapy↗

PubMed1991

Changes in total body water during spaceflight.

This experiment represents the first time that it has been possible to measure a body fluid compartment by direct means during spaceflight. Based on the results observed in the five crewmen in this study, it is concluded that TBW decreases by 3.4% after 1 to 3 days of exposure to microgravity in the Space Shuttle. Some individuals appear to undergo this decrease within 24 hours. This effect may be enhanced by decreased water intake due to nausea associated with SMS.

Adult↗