Postflight Orthostatic Intolerance Research Articles

Changes of loading tensile force–stretch relationships of rabbit mesenteric vein after 21 days of head-down rest

Changes of venous compliance may contribute to postflight orthostatic intolerance; however, direct animal studies to address the changes of venous compliance to microgravity have been rare. The purpose of this study was to determine compliance changes of mesenteric veins of rabbits after 21 days of head-down rest (HDR). Twenty-four healthy male New Zealand Rabbits were randomly divided into 21 days of HDR group, horizontal immobilization group (HIG) and control group (Ctrl), with eight in each. Loading tensile force–stretch relationships of mesenteric vein segments were constructed after 21 d HDR. With the increase of loading tensile force, both longitudinal and circumferential stretches of vein samples increased significantly. Under the same loading tensile force, mesenteric vein of the HDR showed significant increase both in circumferential stretch and longitudinal stretches compared to those of Ctrl group and HIG group. These results indicate that, a 21-day simulated weightlessness leads to increase of mesenteric venous compliance.

Lower body negative pressure exercise plus brief postexercise lower body negative pressure improve post-bed rest orthostatic tolerance

Orthostatic intolerance follows actual weightlessness and weightlessness simulated by bed rest. Orthostasis immediately after acute exercise imposes greater cardiovascular stress than orthostasis without prior exercise. We hypothesized that 5 min/day of simulated orthostasis [supine lower body negative pressure (LBNP)] immediately following LBNP exercise maintains orthostatic tolerance during bed rest. Identical twins (14 women, 16 men) underwent 30 days of 6 degrees head-down tilt bed rest. One of each pair was randomly selected as a control, and their sibling performed 40 min/day of treadmill exercise while supine in 53 mmHg (SD 4) [7.05 kPa (SD 0.50)] LBNP. LBNP continued for 5 min after exercise stopped. Head-up tilt at 60 degrees plus graded LBNP assessed orthostatic tolerance before and after bed rest. Hemodynamic measurements accompanied these tests. Bed rest decreased orthostatic tolerance time to a greater extent in control [34% (SD 10)] than in countermeasure subjects [13% (SD 20); P < 0.004]. Controls exhibited cardiac stroke volume reduction and relative cardioacceleration typically seen after bed rest, yet no such changes occurred in the countermeasure group. These findings demonstrate that 40 min/day of supine LBNP treadmill exercise followed immediately by 5 min of resting LBNP attenuates, but does not fully prevent, the orthostatic intolerance associated with 30 days of bed rest. We speculate that longer postexercise LBNP may improve results. Together with our earlier related studies, these ground-based results support spaceflight evaluation of postexercise orthostatic stress as a time-efficient countermeasure against postflight orthostatic intolerance.

Evaluation of Mechanisms of Postflight Orthostatic Intolerance with a Simple Cardiovascular System Model

A significant fraction of astronauts experience postflight orthostatic intolerance (POI) during 10-min stand tests conducted on landing day. The average time that nonfinishers can stand is about 7 min. This phenomenon, including the delay in occurrence of presyncope, was studied with a five-compartment model of the cardiovascular system incorporating compartments for the heart/lungs, systemic arteries and cephalic, central, and caudal veins. The model included 28 independent parameters, including factors characterizing cardiac performance, vascular resistance, intrathoracic pressure, nonlinear venous compliance and circulating blood volume, and 13 dependent parameters, including cardiac output and cardiac and vascular compartment pressures and volumes. First, a sensitivity analysis of hemodynamic indicators of presyncope to independent parameters was performed. Results demonstrated that both cardiac output and arterial pressure were most sensitive to volume-related parameters, particularly total blood volume, and less sensitive to peripheral resistance. Next, a simulated postflight stand test confirmed that fluid loss due to capillary filtration, particularly from the caudal region where transmural pressure is high during standing, is a plausible mechanism of POI that also explains the delayed onset of symptoms in most astronauts. An accumulated drop in arterial pressure sufficient to compromise cerebral perfusion and, therefore, cause syncope was reached in about 7 min with a fluid loss of 280 mL. Finally, additional simulations showed that a 75% increase in peripheral resistance, similar to finishers of stand tests, was insufficient to overcome the loss of circulating fluid associated with capillary filtration, and extended the time that the modeled astronaut could stand by only about 1 min. It is therefore concluded that capillary filtration may play a key role in producing POI and that development of countermeasures should perhaps focus on reducing postflight capillary permeability or on stimulating volume-compensating mechanisms.

Estradiol and dihydrotestosterone regulate endothelial cell barrier function after hypergravity-induced alterations in MAPK activity

Postflight orthostatic intolerance (POI) was reported to be higher in female than male astronauts and may result from sex-dependent differences in endothelial cell (EC) barrier permeability. Here the effect of 17beta-estradiol (E(2)) and dihydrotestosterone (DHT) on the expression of the tight junction protein occludin, EC barrier function, and MAPK activation over time was tested after subjecting human umbilical vein EC (HUVEC) to brief hypergravity identical to that experienced by astronauts during liftoff (LO) into space. After LO hypergravity, HUVEC showed a time-dependent decrease in occludin correlating with an increase in paracellular permeability and a decrease in transendothelial electrical resistance, indicating a decrease in EC barrier function. LO hypergravity inhibited MAPK activation, which remained suppressed 4 h after LO. Inhibition of MAPK activation correlated with decreased phosphotyrosine occludin, decreased cytochrome-c oxidase activity, and increased paracellular permeability, suggesting a mechanism by which LO hypergravity decreased EC barrier function. Time-dependent differences in MAPK activation, decreased occludin, and EC barrier function between HUVEC treated with E(2) vs. DHT were observed. HUVEC showed delayed activation of MAPK with DHT, i.e., 4 h rather than 2 h for E(2), which correlated with decreased paracellular permeability and the observed sex differences in POI in astronauts. These data temporally separate E(2) and DHT effects in HUVEC and provide evidence for the possible protective roles of sex steroids on EC function after brief exposure to low hypergravity.

Sympathetic nervous system and spaceflight

Purpose: Orthostatic stability on Earth is maintained through sympathetic nerve activation sufficient to increase peripheral vascular resistance and defend against reductions of blood pressure. Orthostatic instability in astronauts upon return from space missions has been linked to blunted vascular resistance responses to standing, introducing the possibility that spaceflight alters normal function between sympathetic efferent traffic and vascular reactivity. Methods: We evaluated published results of spaceflight and relevant ground-based microgravity simulations in an effort to determine responses of the sympathetic nervous system and consequences for orthostatic stability. Results: Direct microneurographic recordings from humans in space revealed that sympathetic nerve activity is increased and preserved in the upright posture after return to Earth (STS-90). However, none of the astronauts studied during STS-90 presented with presyncope postflight, leaving unanswered the question of whether postflight orthostatic intolerance is associated with blunted sympathetic nerve responses or inadequate translation into vascular resistance. Conclusions: There is little evidence to support the concept that spaceflight induces fundamental sympathetic neuroplasticity. The available data seem to support the hypothesis that regardless of whether or not sympathetic traffic is altered during flight, astronauts return with reduced blood volumes and consequent heightened baseline sympathetic activity. Because of this, the ability to withstand an orthostatic challenge postflight is directly proportional to an astronaut's maximal sympathetic activation capacity and remaining sympathetic reserve.

Effects of mechanical unloading on vasoconstriction dynamics in mesenteric resistance vessels

Cephalic fluid shifts inducedby head-down tilt and microgravity alter cardiovascular regulation, resulting in an attenuated ability to regulate blood pressure with sudden postural changes and possibly resulting in orthostatic hypotension. PURPOSE We tested the hypothesis that, consequent to mechanical unloading, mesenteric resistance arteries would demonstrate blunted vasoconstriction dynamics (i.e., slower rate of constriction) versus that of vessels from control animals. METHODS Mesenteric resistance arteries from control (C) and 14-day head-down tail suspension (HDT) rats (6 mo. male Sprague-Dawley) were isolated, cannulated and the rate and magnitude of vasoconstriction to norepinephrine (10−4 M) was quantified via real-time, frame-by-frame analysis (30 frames/s) of luminal diameter. RESULTS Upon exposure to NE, vessels from HDT demonstrated a longer delay before the onset of constriction (HDT, 1.8 ± 0.2 vs. C, 0.9 ± 0.1 s) and a reduced rate of constriction (HDT, 8.4 ± 2.1 vs. C, 13.6 ± 2.6 μm/s). In addition, the time to the steady-state constriction (i.e., no further changes in luminal diameter) was longer in the vessels from HDT rats (HDT, 11.4 ± 1.0 vs. C, 8.0 ± 0.5 s). DISCUSSION These results (i.e., slower rate of vasoconstriction) may provide a mechanistic basis for the increased rate of post-flight orthostatic intolerance. Supported by NASA grant NCC2-1166.

Impaired reflex splanchnic venous constriction may contribute to post‐flight orthostatic intolerance in female astronauts

Astronauts, particularly females, experience post-flight orthostatic intolerance. There is evidence that blood pooling in the splanchnic vasculature, rather than the legs, may be important in females. We proposed that simulated microgravity (hindlimb unloading HLU) would impair reflex mesenteric venoconstriction and mobilization of splanchnic blood. Using intravital microscopy, we investigated the effect of hemorrhage-induced sympathetic activation on mesenteric microvascular tone. Virgin female rats were subjected to HLU at 30o head-down tilt. After 14 days, the animals were anesthetized, positioned on the stage of an inverted microscope, and the mesenteric vascular arcade was viewed using a CCD. After stabilization, they were subjected to a controlled hemorrhage (0.75mL blood/100g body wt.). Real-time alterations in vessel diameter before, during and after hemorrhage were measured by computerized image analysis. As anticipated, hemorrhage induced mesenteric venous constriction in the control animals (no HLU). By contrast, the HLU animals exhibited a significant increase in mesenteric venous diameter. There were no significant changes in mesenteric arterial tone. We propose that impaired reflex mesenteric venous constriction and inadequate mobilization of splanchnic blood may contribute to post-spaceflight orthostatic hypotension, particularly in females. Canadian Space Agency

Effect of estradiol and dihydrotestosterone on hypergravity-induced MAPK signaling and occludin expression in human umbilical vein endothelial cells

Female astronauts have been reported to have a higher incidence of post-flight orthostatic intolerance (POI) compared with that of their male counterparts. POI may result from increased permeability of the endothelial cell (EC) layer in the vasculature. The goal of this study has been to determine whether estradiol (E(2)) and dihydrotesterone (DHT) alter human umbilical vein ECs (HUVECs) responses to short term (10 min) hypergravity (1-3 g) mimicking the g force experienced by astronauts during liftoff. E(2) and DHT rapidly (within 5 min) activated MAPK (mitogen-activated protein kinase) in HUVEC at 1 g in a receptor-dependent manner. Liftoff inhibited MAPK phosphorylation, and rapid E(2) and DHT activation of MAPK was blocked. Liftoff simulation or brief (5-90 min) treatment with E(2) or DHT at 1 g had no effect on the expression of the EC tight-junction protein occludin. However, 24-h pre-treatment of HUVECs with E(2) and DHT prior to liftoff simulation significantly increased occludin expression, and hypergravity exposure did not alter this increase. These data provide evidence for a possible protective effect of E(2) and DHT on EC function as indicated by increased occludin; this may help maintain the integrity of EC tight junction and could thus retard or reduce the incidence of POI.

Accomplishments in bioastronautics research aboard International Space Station

The tenth long-duration expedition crew is currently in residence aboard International Space Station (ISS), continuing a permanent human presence in space that began in October 2000. During that time, expedition crews have been operators and subjects for 18 Human Life Sciences investigations, to gain a better understanding of the effects of long-duration space flight on the crewmembers and of the environment in which they live. Investigations have been conducted to study: the radiation environment in the station as well as during extravehicular activity (EVA); bone demineralization and muscle deconditioning; changes in neuromuscular reflexes; muscle forces and postflight mobility; causes and possible treatment of postflight orthostatic intolerance; risk of developing kidney stones; changes in pulmonary function caused by long-duration flight as well as EVA; crew and crew–ground interactions; changes in immune function, and evaluation of imaging techniques. The experiment mix has included some conducted in flight aboard ISS as well as several which collected data only pre- and postflight. The conduct of these investigations has been facilitated by the Human Research Facility (HRF). HRF Rack 1 became the first research rack on ISS when it was installed in the US laboratory module Destiny in March 2001. The rack provides a core set of experiment hardware to support investigations, as well as power, data and commanding capability, and stowage. The second HRF rack, to complement the first with additional hardware and stowage capability, will be launched once Shuttle flights resume. Future years will see additional capability to conduct human research on ISS as International Partner modules and facility racks are added to ISS. Crew availability, both as a subject count and time, will remain a major challenge to maximizing the science return from the bioastronautics research program.

Artificial gravity: A possible countermeasure for post-flight orthostatic intolerance

Four payload crewmembers were exposed to sustained linear acceleration in a centrifuge during the Neurolab (STS-90) flight. In contrast to previous studies, otolith–ocular reflexes were preserved during and after flight. This raised the possibility that artificial gravity may have acted as a countermeasure to the deconditioning of otolith–ocular reflexes. None of the astronauts who were centrifuged had orthostatic intolerance when tested with head-up passive tilt after flight. Thus, centrifugation may also have helped maintain post-flight hemodynamic responses to orthostasis by preserving the gain of the otolith–sympathetic reflex. A comparison with two fellow Neurolab orbiter crewmembers not exposed to artificial gravity provided some support for this hypothesis. One of the two had hemodynamic changes in response to post-flight tilt similar to orthostatically intolerant subjects from previous missions. More data is necessary to evaluate this hypothesis, but if it were proven correct, in-flight short-radius centrifugation may help counteract orthostatic intolerance after space flight.

Quantification of left ventricular modification in weightlessness conditions from the spatio-temporal analysis of 2D echocardiographic images

Two-dimensional echocardiography (2DE) performed during flights with a parabolic trajectory to simulate weightlessness provides a unique means to study left ventricular (LV) modifications to prevent post-flight orthostatic intolerance in astronauts. However, conventional analysis of 2DE is based on manual tracings and depends on experience. Accordingly, the aim was objectively to quantify, from 2DE images, the LV modifications related to different gravity levels, by applying a semi-automated level-set border detection technique. The algorithm validation was performed by the comparison of manual tracing results, obtained by two independent observers with 20 images, with the semi-automated measurements. To quantify LV modifications, three consecutive cardiac cycles were analysed for each gravity phase (1 Gz, 1.8 Gz, 0 Gz). The level-set procedure was applied frame-by-frame to detect the LV endocardial contours and obtain LV area against time curves, from which end-diastolic (EDA) and end-systolic (ESA) areas were computed and averaged to compensate for respiratory variations. Linear regression (y = 0.91x + 1.47, r = 0.99, SEE:0.80cm2) and Bland-Altman analysis (bias = -0.58 cm2, 95% limits of agreement= +/- 2.14cm2) showed excellent correlation between the semi-automatic and manually traced values. Inter-observer variability was 5.4%, and the inter-technique variability was 4.1%. Modifications in LV dimensions during the parabola were found: compared with 1 Gz values, EDA and ESA were significantly reduced at 1.8 Gz by 8.8 +/- 5.5% and 12.1 +/- 10.1%, respectively, whereas, during 0 Gz, EDA and ESA increased by 13.3 +/- 7.3% and 11.6 +/- 5.1%, respectively, owing to abrupt changes in venous return. The proposed method resulted in fast and reliable estimations of LV dimensions, whose changes caused by different gravity conditions were objectively quantified.

Heart rate variability and short duration spaceflight: relationship to post-flight orthostatic intolerance

BackgroundUpon return from space many astronauts experience symptoms of orthostatic intolerance. Research has implicated altered autonomic cardiovascular regulation due to spaceflight with further evidence to suggest that there might be pre-flight autonomic indicators of post-flight orthostatic intolerance. We used heart rate variability (HRV) to determine whether autonomic regulation of the heart in astronauts who did or did not experience post-flight orthostatic intolerance was different pre-flight and/or was differentially affected by short duration (8 – 16 days) spaceflight. HRV data from ten-minute stand tests collected from the 29 astronauts 10 days pre-flight, on landing day and three days post-flight were analysed using coarse graining spectral analysis. From the total power (PTOT), the harmonic component was extracted and divided into high (PHI: >0.15 Hz) and low (PLO: = 0.15 Hz) frequency power regions. Given the distribution of autonomic nervous system activity with frequency at the sinus node, PHI/PTOT was used as an indicator of parasympathetic activity; PLO/PTOT as an indicator of sympathetic activity; and, PLO/PHI as an estimate of sympathovagal balance.ResultsTwenty-one astronauts were classified as finishers, and eight as non-finishers, based on their ability to remain standing for 10 minutes on landing day. Pre-flight, non-finishers had a higher supine PHI/PTOT than finishers. Supine PHI/PTOT was the same pre-flight and on landing day in the finishers; whereas, in the non-finishers it was reduced. The ratio PLO/PHI was lower in non-finishers compared to finishers and was unaffected by spaceflight. Pre-flight, both finishers and non-finishers had similar supine values of PLO/PTOT, which increased from supine to stand. Following spaceflight, only the finishers had an increase in PLO/PTOT from supine to stand.ConclusionsBoth finishers and non-finishers had an increase in sympathetic activity with stand on pre-flight, yet only finishers retained this response on landing day. Non-finishers also had lower sympathovagal balance and higher pre-flight supine parasympathetic activity than finishers. These results suggest pre-flight autonomic status and post-flight impairment in autonomic control of the heart may contribute to orthostatic intolerance. The mechanism by which higher pre-flight parasympathetic activity might contribute to post-flight orthostatic intolerance is not understood and requires further investigation.

Numerical simulation of the influence of gravity and posture on cardiac performance.

A numerical model of the cardiovascular system was used to quantify the influences on cardiac function of intrathoracic pressure and intravascular and intraventricular hydrostatic pressure, which are fundamental biomechanical stimuli for orthostatic response. The model included a detailed arterial circulation with lumped parameter models of the atria, ventricles, pulmonary circulation, and venous circulation. The venous circulation was divided into cranial, central, and caudal regions with nonlinear compliance. Changes in intrathoracic pressure and the effects of hydrostatic pressure were simulated in supine, launch, sitting, and standing postures for 0, 1, and 1.8 G. Increasing intrathoracic pressure experienced with increasing gravity caused 12% and 14% decreases in cardiac output for 1 and 1.8 G supine, respectively, compared to 0 G. Similar results were obtained for launch posture, in which the effects of changing intrathoracic pressure dominated those of hydrostatic pressure. Compared to 0 G, cardiac output decreased 0.9% for 1 G launch and 15% for 1.8 G launch. In sitting and standing, the position of the heart above the hydrostatic indifference level caused the effects of changing hydrostatic pressure to dominate those of intrathoracic pressure. Compared to 0 G, cardiac output decreased 13% for 1 G sitting and 23% for 1.8 G sitting, and decreased 17% for 1 G standing and 31% for 1.8 G standing. For a posture change from supine to standing in 1 G, cardiac output decreased, consistent with the trend necessary to explain orthostatic intolerance in some astronauts during postflight stand tests. Simulated lower body negative pressure (LBNP) in 0 G reduced cardiac output and mean aortic pressure similar to I G standing, suggesting that LBNP provides at least some cardiovascular stimuli that may be useful in preventing postflight orthostatic intolerance. A unifying concept, consistent with the Frank-Starling mechanism of the heart, was that cardiac output was proportional to cardiac diastolic transmural pressure for all postures and gravitational accelerations.

Vascular adaptation to microgravity: what have we learned?

Findings from recent bed rest and spaceflight human studies have indicated that the inability to adequately elevate the peripheral resistance and the altered autoregulation of cerebral vasculature are important factors in postflight orthostatic intolerance. Animal studies with rat model have revealed that simulated microgravity may induce upward and downward regulations in the structure, function, and innervation of the cerebral and hindquarter vessels. These findings substantiate in general the hypothesis that microgravity-induced redistribution of transmural pressures and flows across and within the arterial vasculature may well initiate differential adaptations of vessels in different anatomic regions. Understanding of the mechanisms involved in vascular adaptation to microgravity is also important for the development of multisystem countermeasures. However, future studies will be required to further ascertain the peripheral effector mechanism of postflight cardiovascular dysfunction.

Heart rate variability after prolonged spaceflights

Astronauts returning from spaceflight often experience post-flight orthostatic intolerance. This study was designed to determine whether cosmonauts with post-flight syncope could be distinguished from those with no post-flight syncope. The autonomic function was determined in a group of ten subjects, with no previous history of syncope, during a stand test before and after a long-term spaceflight (90 to 198 days). Heart rate (HR) and systolic blood pressure (SBP) were measured beat-by-beat, pre- and post-flight and the spontaneous baroreflex sensitivity and HR variability were studied. Individuals were categorized according to their ability to remain standing for 5 min the day after landing. Three of the ten cosmonauts failed to finish the standing test performed the day after landing (nonfinishers). The spontaneous baroreflex slope was reduced in both groups after the spaceflight. The non-finisher group had a lower SBP (P < 0.05) at rest in pre-flight tests than the group that completed the test (finisher group). The non-finisher group also had higher indicators of parasympathetic activity when supine, both pre- and post-flight, but this difference disappeared with standing. At the end of the stand test, SBP and HR were lower in non-finisher cosmonauts than the finishers, while HR did not increase compared to early measurements in the stand test of the finisher group. These results suggest an impairment in autonomic control of HR, which might contribute to the fainting response.

Effects of spaceflight on human calf hemodynamics.

Chronic microgravity may modify adaptations of the leg circulation to gravitational pressures. We measured resting calf compliance and blood flow with venous occlusion plethysmography, and arterial blood pressure with sphygmomanometry, in seven subjects before, during, and after spaceflight. Calf vascular resistance equaled mean arterial pressure divided by calf flow. Compliance equaled the slope of the calf volume change and venous occlusion pressure relationship for thigh cuff pressures of 20, 40, 60, and 80 mmHg held for 1, 2, 3, and 4 min, respectively, with 1-min breaks between occlusions. Calf blood flow decreased 41% in microgravity (to 1.15 +/- 0.16 ml x 100 ml(-1) x min(-1)) relative to 1-G supine conditions (1.94 +/- 0.19 ml x 100 ml(-1) x min(-1), P = 0.01), and arterial pressure tended to increase (P = 0.05), such that calf vascular resistance doubled in microgravity (preflight: 43 +/- 4 units; in-flight: 83 +/- 13 units; P < 0.001) yet returned to preflight levels after flight. Calf compliance remained unchanged in microgravity but tended to increase during the first week postflight (P > 0.2). Calf vasoconstriction in microgravity qualitatively agrees with the "upright set-point" hypothesis: the circulation seeks conditions approximating upright posture on Earth. No calf hemodynamic result exhibited obvious mechanistic implications for postflight orthostatic intolerance.

Baroreflex dysfunction induced by microgravity: potential relevance to postflight orthostatic intolerance.

Microgravity imposes adaptive changes in the human body. This review focuses on the changes in baroreflex function produced by actual spaceflight, or by experimental models that simulate microgravity, e.g., bed rest. We will analyze separately studies involving baroreflexes arising from carotid sinus and aortic arch afferents ("high-pressure baroreceptors"), and cardiopulmonary afferents ("low-pressure receptors"). Studies from unrelated laboratories using different techniques have concluded that actual or simulated exposure to microgravity reduces baroreflex function arising from carotid sinus afferents ("carotic-cardiac baroreflex"). The techniques used to study the carotid-cardiac baroreflex, using neck suction and compression to simulate changes in blood pressure, have been extensively validated. In contrast, it is more difficult to selectively study aortic arch or cardiopulmonary baroreceptors. Nonetheless, studies that have examined these baroreceptors suggest that microgravity produces the opposite effect, ie, an increase in the gain of aortic arch and cardiopulmonary baroreflexes. Furthermore, most studies have focus on instantaneous changes in heart rate, which almost exclusively examines the vagal limb of the baroreflex. In comparison, there is limited information about the effect of microgravity on sympathetic function. A substantial proportion of subjects exposed to microgravity develop transient orthostatic intolerance. It has been proposed that alterations in baroreflex function play a role in the orthostatic intolerance induced by microgravity. The evidence in favor and against this hypothesis is reviewed.

Physiology in microgravity.

Studies of physiology in microgravity are remarkably recent, with almost all the data being obtained in the past 40 years. The first human spaceflight did not take place until 1961. Physiological measurements in connection with the early flights were crude, but, in the past 10 years, an enormous amount of new information has been obtained from experiments on Spacelab. The United States and Soviet/Russian programs have pursued different routes. The US has mainly concentrated on relatively short flights but with highly sophisticated equipment such as is available in Spacelab. In contrast, the Soviet/Russian program concentrated on first the Salyut and then the Mir space stations. These had the advantage of providing information about long-term exposure to microgravity, but the degree of sophistication of the measurements in space was less. It is hoped that the International Space Station will combine the best of both approaches. The most important physiological changes caused by microgravity include bone demineralization, skeletal muscle atrophy, vestibular problems causing space motion sickness, cardiovascular problems resulting in postflight orthostatic intolerance, and reductions in plasma volume and red cell mass. Pulmonary function is greatly altered but apparently not seriously impaired. Space exploration is a new frontier with long-term missions to the moon and Mars not far away. Understanding the physiological changes caused by long-duration microgravity remains a daunting challenge.

Chapter 6 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.

Microgravity decreases heart rate and arterial pressure in humans.

Spaceflight causes adaptive changes in cardiovascular physiology, such as postflight orthostatic intolerance, that can have deleterious effects on astronauts. In-flight cardiovascular data are difficult to obtain, and results have been inconsistent. To determine normative in-flight changes in Shuttle astronauts, we measured heart rate, arterial pressure, and cardiac rhythm disturbances for 24-h periods before, during, and after spaceflight on Shuttle astronauts performing their normal routines. We found that heart rate, diastolic pressure, variability of heart rate and diastolic pressure, and premature ventricular contractions all were significantly reduced in flight. Systolic pressure and premature atrial contractions also tended to be reduced in flight. These data constitute the first systematic evaluation of in-flight changes in basic cardiovascular variables in Shuttle astronauts and suggest that a microgravity environment itself does not present a chronic stress to the cardiovascular system.