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Endocrine relationships during human spaceflight

Human spaceflight is associated with a chronic loss of protein from muscle. The objective of this study was to determine whether changes in urinary hormone excretion could identify a hormonal role for this loss. Urine samples were collected from the crews of two Life Sciences Space Shuttle missions before and during spaceflight. Data are means +/- SE with the number of subjects in parentheses. The first value is the mean preflight measurement, and the second value is the mean inflight measurement. Adrenocorticotropic hormone (ACTH) [27.7 +/- 4.4 (9) vs. 25.1 +/- 3.4 (9) ng/day], growth hormone [724 +/- 251 (9) vs. 710 +/- 206 (9) ng/day], insulin-like growth factor I [6.81 +/- 0.62 vs. 6.04 +/- 0.51 (8) nM/day], and C-peptide [44.9 +/- 8.3 (9) vs. 50.7 +/- 10.3 (9) micrograms/day] were unchanged with spaceflight. In contrast, free 3,5,3'-triiodothyronine [791 +/- 159 (9) vs. 371 +/- 41 (9) pg/day, P < 0.05], prostaglandin E2 (PGE2) [1, 064 +/- 391 (8) vs. 465 +/- 146 (8) ng/day, P < 0.05], and its metabolite PGE-M [1,015 +/- 98 (9) vs. 678 +/- 105 (9) ng/day, P < 0. 05] were decreased inflight. The urinary excretion of most hormones returned to their preflight levels during the postflight period, with the exception of ACTH [47.5 +/- 10.3 (9) ng/day], PGE2 [1,433 +/- 327 (8) ng/day], PGF2alpha, [2,786 +/- 313 (8) ng/day], and its metabolite PGF-M [4,814 +/- 402 (9) ng/day], which were all increased compared with the preflight measurement (P < 0.05). There was a trend for urinary cortisol to be elevated inflight [55.3 +/- 5. 9 (9) vs. 72.5 +/- 11.1 micrograms/day, P = 0.27] and postflight [82.7 +/- 8.6 (8) micrograms/day, P = 0.13]. The inflight human data support ground-based in vitro work showing that prostaglandins have a major role in modulating the changes in muscle protein content in response to tension or the lack thereof.

Flight Experiment

Touch-plate and statolith formation in graviceptors of ephyrae which developed while weightless in space

Ultrastructural studies of the statocysts and touch-plates of graviceptors (rhopalia) of Aurelia ephyrae revealed that (1) touch-plate hair cells are present; and (2) cytoplasmic strands from the hair cell bases extend from the neurite plexus to touch similar strands from the lithocytes. This close association of hair cell neurites and statocysts may have important implications regarding the transmitting and processing of positional information with respect to the gravity vector. Graviceptors of ephyrae which developed while weightless in microgravity were compared with controls at the ultrastructural level. We found that hair cells of ephyrae which developed in microgravity had fewer lipid droplets in the large spaces near their bases as compared with 1 g controls. In the ephyrae from the first microgravity experiment, hair cells had more large apical vacuoles with filamentous content than were found in hair cells of ephyrae from the second experiment and controls. The neurite plexus and the network of cytoplasmic strands extending to the statocysts were not different in microgravity-developed ephyrae from controls. Behavioral differences in swimming and orienting in ephyrae in microgravity and controls (reported earlier) were not explained by morphological differences in the hair cells of the touch-plates or the statocysts, although functional differences apparently occurred.

NASA Discipline Developmental Biology

Synaptic changes in rat maculae in space and medical imaging: the link

Two different space life sciences missions (SLS-1 and SLS-2) have demonstrated that the synapses of the hair cells of rat vestibular maculae increase significantly in microgravity. The results also indicate that macular synapses are sensitive to stress. These findings argue that vestibular maculae exhibit neuroplasticity to macroenvironmental and microenvironmental changes. This capability should be clinically relevant to rehabilitative training and/or pharmacological treatments for vestibular disease. The results of this ultrastructural research also demonstrated that type I and type II hair cells are integrated into the same neuronal circuitry. The findings were the basis for development of three-dimensional reconstruction software to learn details of macular wiring. This software, produced for scientific research, has now been adapted to reconstruct the face and skull directly from computerized tomography scans. In collaboration with craniofacial reconstructive surgeons at Stanford University Medical Center, an effort is under way to produce a virtual environment workbench for complex craniofacial surgery. When completed, the workbench will help surgeons train for and simulate surgery. The methods are patient specific. This research illustrates the value of basic research in leading to unanticipated medical applications.

Flight Experiment

Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity

In microgravity (microG) humans have marked changes in body fluids, with a combination of an overall fluid loss and a redistribution of fluids in the cranial direction. We investigated whether interstitial pulmonary edema develops as a result of a headward fluid shift or whether pulmonary tissue fluid volume is reduced as a result of the overall loss of body fluid. We measured pulmonary tissue volume (Vti), capillary blood flow, and diffusing capacity in four subjects before, during, and after 10 days of exposure to microG during spaceflight. Measurements were made by rebreathing a gas mixture containing small amounts of acetylene, carbon monoxide, and argon. Measurements made early in flight in two subjects showed no change in Vti despite large increases in stroke volume (40%) and diffusing capacity (13%) consistent with increased pulmonary capillary blood volume. Late in-flight measurements in four subjects showed a 25% reduction in Vti compared with preflight controls (P < 0.001). There was a concomittant reduction in stroke volume, to the extent that it was no longer significantly different from preflight control. Diffusing capacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despite increased pulmonary perfusion and pulmonary capillary blood volume, interstitial pulmonary edema does not result from exposure to microG.

Clinical Trial

Pulmonary function in space

The lung is exquisitely sensitive to gravity, and so it is of interest to know how its function is altered in the weightlessness of space. Studies on National Aeronautics and Space Administration (NASA) Spacelabs during the last 4 years have provided the first comprehensive data on the extensive changes in pulmonary function that occur in sustained microgravity. Measurements of pulmonary function were made on astronauts during space shuttle flights lasting 9 and 14 days and were compared with extensive ground-based measurements before and after the flights. Compared with preflight measurements, cardiac output increased by 18% during space flight, and stroke volume increased by 46%. Paradoxically, the increase in stroke volume occurred in the face of reductions in central venous pressure and circulating blood volume. Diffusing capacity increased by 28%, and the increase in the diffusing capacity of the alveolar membrane was unexpectedly large based on findings in normal gravity. The change in the alveolar membrane may reflect the effects of uniform filling of the pulmonary capillary bed. Distributions of blood flow and ventilation throughout the lung were more uniform in space, but some unevenness remained, indicating the importance of nongravitational factors. A surprising finding was that airway closing volume was approximately the same in microgravity and in normal gravity, emphasizing the importance of mechanical properties of the airways in determining whether they close. Residual volume was unexpectedly reduced by 18% in microgravity, possibly because of uniform alveolar expansion. The findings indicate that pulmonary function is greatly altered in microgravity, but none of the changes observed so far will apparently limit long-term space flight. In addition, the data help to clarify how gravity affects pulmonary function in the normal gravity environment on Earth.

short duration

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.

NASA Discipline Number 18-10

Animal models and their importance to human physiological responses in microgravity

Two prominent theories to explain the physiological effects of microgravity relate to the cascade of changes associated with the cephalic shifts of fluids and the absence of tissue deformation forces. One-g experiments for humans used bed rest and the head-down tilt (HDT) method, while animal experiments have been conducted using the tail-suspended, head-down, and hindlimbs non-weightbearing model. Because of the success of the HDT approach with rats to simulate the gravitational effects on the musculoskeletal system exhibited by humans, the same model has been used to study the effects of gravity on the cardiopulmonary systems of humans and other vertebrates. Results to date indicate the model is effective in producing comparable changes associated with blood volume, erythropoiesis, cardiac mass, baroreceptor responsiveness, carbohydrate metabolism, post-flight VO2max, and post-flight cardiac output during exercise. Inherent with these results is the potential of the model to be useful in investigating responsible mechanisms. The suspension model has promise in understanding the capillary blood PO2 changes in space as well as the arterial PO2 changes in subjects participating in a HDT experiment. However, whether the model can provide insights on the up-or-down regulation of adrenoreceptors remains to be determined, and many investigators believe the HDT approach should not be followed to study gravitational influences on pulmonary function in either humans or animals. It was concluded that the tail-suspended animal model had sufficient merit to study in-flight and post-flight human physiological responses and mechanisms.

NASA Discipline Cardiopulmonary

Cardiovascular adaptation to spaceflight

This article reviews recent flight and ground-based studies of cardiovascular adaptation to spaceflight. Prominent features of microgravity exposure include loss of gravitational pressures, relatively low venous pressures, headward fluid shifts, plasma volume loss, and postflight orthostatic intolerance and reduced exercise capacity. Many of these short-term responses to microgravity extend themselves during long-duration microgravity exposure and may be explained by altered pressures (blood and tissue) and fluid balance in local tissues nourished by the cardiovascular system. In this regard, it is particularly noteworthy that tissues of the lower body (e.g., foot) are well adapted to local hypertension on Earth, whereas tissues of the upper body (e.g., head) are not as well adapted to increase in local blood pressure. For these and other reasons, countermeasures for long-duration flight should include reestablishment of higher, Earth-like blood pressures in the lower body.

Review, Tutorial

Substrate oxidation capacity in rodent skeletal muscle: effects of exposure to zero gravity

A study was conducted, as part of the integrated National Aeronautics and Space Administration Space Life Sciences 1 mission flown in June of 1991, to ascertain the effects of 9 days of exposure to zero gravity on the capacity of rodent skeletal muscle fiber types to oxidize either [14C]pyruvate or [14C]palmitate under state 3 metabolic conditions, i.e., nonlimiting amounts of substrate and cofactors. In addition, activity levels of marker enzymes of the tricarboxylic acid cycle, malate shuttle, and beta-oxidation were measured. Results showed that significant differences in muscle weight occurred in both the predominantly slow vastus intermedius and predominantly fast vastus lateralis of flight vs. control groups (P < 0.05). Total protein content of the muscle samples was similar between groups. Both pyruvate oxidation capacity and the marker oxidative enzymes were not altered in the flight relative to control animals. However, the capacity to oxidize long-chain fatty acids was significantly reduced by 37% in both the high- and low-oxidative regions of the vastus muscle (P < 0.05). Although these findings of a selective reduction in fatty acid oxidation capacity in response to spaceflight are surprising, they are consistent with previous findings showing 1) an increased capacity to take up glucose and upregulate glucose transporter proteins and 2) a marked accumulation of triglycerides in the skeletal muscles of rats subjected to states of unloading. Thus, skeletal muscle of animals exposed to non-weight-bearing environments undergo subcellular transformations that may preferentially bias energy utilization to carbohydrates.

NASA Discipline Musculoskeletal

Myosin heavy chain expression in rodent skeletal muscle: effects of exposure to zero gravity

This study ascertained the effects of 9 days of zero gravity on the relative (percentage of total) and calculated absolute (mg/muscle) content of isomyosin expressed in both antigravity and locomotor skeletal muscle of ground control (CON) and flight-exposed (FL) rats. Results showed that although there were no differences in body weight between FL and CON animals, a significant reduction in muscle mass occurred in the vastus intermedius (VI) (P < 0.05) but not in the vastus lateralis (VL) or the tibialis anterior. Both total muscle protein and myofibril protein content were not different between the muscle regions examined in the FL and CON groups. In the VI, there were trends for reductions in the relative content of type I and IIa myosin heavy chains (MHCs) that were offset by increases in the relative content of both type IIb and possibly type IIx MHC protein (P > 0.05). mRNA levels were consistent with this pattern (P < 0.05). The same pattern held true for the red region of the VL as examined at both the protein and mRNA level (P < 0.05). When the atrophy process was examined, there were net reductions in the absolute content of both type I and IIa MHCs that were offset by calculated increases in type IIb MHC in both VI and red VL. Collectively, these findings suggest that there are both absolute and relative changes occurring in MHC expression in the "red" regions of antigravity skeletal muscle during exposure to zero gravity that could affect muscle function.

short duration

Mitogenic signal transduction in T lymphocytes in microgravity

The activation by concanavalin A Con A of human peripheral blood lymphocytes (PBLs) in the presence of monocytes as accessory cells was investigated in cultures exposed to microgravity conditions in Spacelab. Activation of T cells was measured as incorporation of [3H]thymidine into DNA, secretion of interleukin-2 (IL-2), and interferon-gamma, and expression of IL-2 receptors. Whereas, as discovered in earlier experiments, the activation of resuspended T cells is strongly inhibited, activation of cells attached to microcarrier beads is more than doubled in microgravity. The results suggest that the depression of the activation in resuspended cells may be attributed to a malfunction of monocytes acting as accessory cells. In fact, although the ultrastructure of resuspended monocytes is not altered in microgravity, the secretion of IL-1 is strongly inhibited. Our data suggest that (1) IL-2 is produced independently of IL-1, (2) IL-1 production is triggered only when monocytes (and lymphocytes?) adhere to microcarriers, (3) the expression of IL-2 receptors depends on IL-1, and (4) provided sufficient IL-1 is available, activation is enhanced in microgravity. Finally, cultures of resuspended PBLs and monocytes in microgravity constitute a complete and natural system in which monocytes are not operational. This may be useful for studies of the role of accessory cells and cell-cell interactions in T lymphocyte activation.

STS-40 Shuttle Project

Horizontal angular VOR, nystagmus dumping, and sensation duration in spacelab SLS-1 crewmembers

In 1G, the apparent time constant (Td) of postrotatory SPV decay with the head tilted face down is 55% of that with head erect (Te). This phenomenon is called "nystagmus dumping" and has been attributed to G effects on VOR velocity storage. Similarly, postrotatory sensation duration with head tilted (Dd) is 32% of that when head erect (De). In parabolic flight, Te and De are 70% of 1-G values, but a pitch back dumping movement produces no further change. Te, Td, and Dd have not previously been measured in orbital flight. VOR and sensation duration was tested in 4 crewmembers in 4 preflight, 1 inflight (days 4 or 5) and 4 post flight sessions. Bitemporal EOG was recorded with eyes open in darkness. Instructions were to "gaze straight ahead," and indicate when "rotation sensation disappears or becomes ambiguous". Subjects were rotated CW and CCW head erect for 1 min at 120 degrees/s, stopped, and EOG was recorded for another 1 min. This procedure was then used to study dumping, except that immediately after chair stop, subjects pitched their head forward 90 degrees. SPV was calculated using order statistic filtering, and dropouts removed using an iterative model fitting method. Te and Td were determined by logarithmic linear regression of mean SPV for each subject. In orbit, 90 degrees pitch movement produced rapid subjective dumping, but not nystagmus dumping. Dd was noticeably shorter ("almost instantaneous") compared to preflight Dd. Te and Td in orbit were similar to preflight Te for 3/4 subjects (rather than to preflight Td as expected). No consistent VOR gain changes were seen in orbit. Although Te is known to decrease acutely in parabolic flight, a longer time constant was measured in 3/4 subjects after 4-5 days adaptation to weightlessness, suggesting a return of angular velocity storage.

NASA Experiment Number 178072 1/2

Pulmonary function in microgravity

We report the successful collection of a large quantity of human resting pulmonary function data on the SLS-1 mission. Preliminary analysis suggests that cardiac stroke volumes are high on orbit, and that an adaptive reduction takes at least several days, and in fact may still be in progress after 9 days on orbit. It also suggests that pulmonary capillary blood volumes are high, and remain high on orbit, but that the pulmonary interstitium is not significantly impacted. The data further suggest that the known large gravitational gradients of lung function have only a modest influence on single breath tests such as the SBN washout. They account for only approximately 25% of the phase III slope of nitrogen, on vital capacity SBN washouts. These gradients are only a moderate source of the cardiogenic oscillations seen in argon (bolus gas) and nitrogen (resident gas), on such tests. They may have a greater role in generating the normal CO2 oscillations, as here the phase relationship to argon and nitrogen reverses in microgravity, at least at mid exhalation in those subjects studied to date. Microgravity may become a useful tool in establishing the nature of the non-gravitational mechanisms that can now be seen to play such a large part in the generation of intra-breath gradients and oscillations of expired gas concentration. Analysis of microgravity multibreath nitrogen washouts, single breath washouts from more physiological pre-inspiratory volumes, both using our existing SLS-1 data, and data from the upcoming D-2 and SLS-2 missions, should be very fruitful in this regard.(ABSTRACT TRUNCATED AT 250 WORDS).

manned

Review of the biological effects of weightlessness on the human endocrine system

Studies from space flights over the past two decades have demonstrated that there are basic physiological changes in humans during space flight. These changes include cephalad fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known but the general approach has been to investigate systemic and hormonal changes. However, data from the 1973-1974 Skylabs, Spacelab 3 (SL-3), Spacelab D-I (SL-DI), and now the new SLS-1 missions support a more basic biological response to microgravity that may occur at the tissue, cellular, and molecular level. This report summarizes ground-based and SLS-1 experiments that examined the mechanism of loss of red blood cell mass in humans, the loss of bone mass and lowered osteoblast growth under space flight conditions, and loss of immune function in microgravity.

STS-40 Shuttle Project

Summary Status of the Space Acceleration Measurement System (SAMS), September 1993

The Space Acceleration Measurement System (SAMS) was developed to measure the microgravity acceleration environment to which NASA science payloads are exposed during microgravity science missions on the shuttle. Six flight units have been fabricated to date. The inaugural flight of a SAMS unit was on STS-40 in June 1991 as part of the flrst Spacelab Life Sciences mission. Since that time, SAMS has flown on six additional missions and gathered 18 gigabytes of data representing 68 days of microgravity environment. The SAMS units have been flown in the shuttle middeck and cargo bay, in the Spacelab module, and in the Spacehab module. This paper summarizes the missions and experiments which SAMS has supported. The quantity of data and the utilization of the SAMS data is described. Future activities are briefly described for the SAMS project and.the Microgravity Measurement and Analysis Project (MMAP) to support science experiments and scientists with microgravity environment measurement and analysis.

DeLombard, Richard