Control of red blood cell mass during spaceflight

Data are reviewed from twenty-two astronauts from seven space missions in a study of red blood cell mass. The data show that decreased red cell mass in all astronauts exposed to space for more than nine days, although the actual dynamics of mass changes varies with flight duration. Possible mechanisms for these changes, including alterations in erythropoietin levels, are discussed.     

Lipid peroxidation rate and the antioxidant protection system during the readaptation period after long-term space flights on board the International Space Station

The content of lipid peroxidation (LPO) products (diene conjugates (DC), malondialdehyde (MDA), Schiff bases (SB), and tocopherol (TP, a main lipid antioxidant) were measured in blood serum of 17 astronauts taking part in long-term (125–217 days) missions on board the International Space Station (ISS) during the preflight period, on the day of the landing, and on the 7th and 14th days after landing (the rehabilitation period, RP). A decrease in the DC and MDA levels against a background of an increase in TP has been found in a group of eight astronauts after landing on board the Space Shuttle spacecraft and a group of eight astronauts after a space flight on board the Soyuz TM in the course of RP. The changes in measured indices were more pronounced in the group of astronauts after the space flight on board the Space Shuttle spacecraft. Inhibition of LPO during RP was regarded as an adequate response to readaptation stress to the conditions on earth. The possible mechanisms of differences in the efficiency of LPO inhibition between groups are discussed: the changes in the biomembrane phase state under the conditions of deceleration load during disorbiting and the stressful reaction to landing on board different spacecrafts.     

Effect of microgravity on plasma catecholamine responses to stressors during space flight

The effect of microgravity on the sympathicoadrenal system (SAS) activity in humans and animals has not yet been clarified. Our previous studies suggested that the SAS activity, evaluated by circulating and/or urinary catecholamine (CA) levels in astronauts during space flights, was found to be rather unchanged. However, CA levels were measured in astronauts only at rest conditions. The aim of the present study was to investigate effect of microgravity during space flight and post-flight readaptation on responsiveness of the SAS to somatic and psychic stressors evaluated by levels of catecholamines and their metabolite in the blood of the Slovak cosmonaut during his stay on board the space station Mir.     

Biological and metabolic response in STS-135 space-flown mouse skin

Abstract

There is evidence that space flight condition-induced biological damage is associated with increased oxidative stress and extracellular matrix (ECM) remodeling. To explore possible mechanisms, changes in gene expression profiles implicated in oxidative stress and in ECM remodeling in mouse skin were examined after space flight. The metabolic effects of space flight in skin tissues were also characterized. Space Shuttle Atlantis (STS-135) was launched at the Kennedy Space Center on a 13-day mission. Female C57BL/6 mice were flown in the STS-135 using animal enclosure modules (AEMs). Within 3–5 h after landing, the mice were euthanized and skin samples were harvested for gene array analysis and metabolic biochemical assays. Many genes responsible for regulating production and metabolism of reactive oxygen species (ROS) were significantly (p < 0.05) altered in the flight group, with fold changes >1.5 compared to AEM control. For ECM profile, several genes encoding matrix and metalloproteinases involved in ECM remodeling were significantly up-/down-regulated following space flight. To characterize the metabolic effects of space flight, global biochemical profiles were evaluated. Of 332 named biochemicals, 19 differed significantly (p < 0.05) between space flight skin samples and AEM ground controls, with 12 up-regulated and 7 down-regulated including altered amino acid, carbohydrate metabolism, cell signaling, and transmethylation pathways. Collectively, the data demonstrated that space flight condition leads to a shift in biological and metabolic homeostasis as the consequence of increased regulation in cellular antioxidants, ROS production, and tissue remodeling. This indicates that astronauts may be at increased risk for pathophysiologic damage or carcinogenesis in cutaneous tissue.     

Space radiation does not induce a significant increase of intrachromosomal exchanges in astronauts’ lymphocytes

Chromosome aberration analysis in astronauts has been used to provide direct, biologically motivated estimates of equivalent doses and risk associated to cosmic radiation exposure during space flight. However, the past studies concentrated on measurements of dicentrics and translocations, while chromosome intrachanges (inversions) have never been measured in astronauts’ samples. Recent data reported in the literature suggest that densely ionizing radiation can induce a large fraction of intrachanges, thus leading to the suspicion that interchanges grossly underestimate the cosmic radiation-induced cytogenetic damage in astronauts. We have analyzed peripheral blood lymphocytes from 11 astronauts involved in short- or long-term space flights in low-Earth orbit using high-resolution multicolor banding to assess the frequency of intrachromosomal exchanges in both pre- and post-flight samples. We did not detect any inversions in chromosome 5 from a total of 2800 cells in astronauts’ blood. In addition, no complex type exchanges were found in a total of 3590 astronauts’ lymphocytes analyzed by multifluor fluorescence in situ hybridisation. We conclude that, within the statistical power of this study, the analysis of interchanges for biological dosimetry in astronauts does not significantly underestimate the space radiation-induced cytogenetic damage, and complex-type exchanges or intrachanges have limited practical use for biodosimetry at very low doses.     

Relationship between stroke volume and sympathetic nerve activity: new insights about autonomic mechanisms of syncope

Head-up tilt table experiments conducted in astronauts prior to and immediately after the NASA Neurolab Space Mission (STS-90) revealed that a reduction in stroke volume induced by moving from the supine to upright posture was associated with increased muscle sympathetic nerve activity (MSNA). Although this finding was not unexpected, lower average stroke volume and greater average MSNA measured after space flight in both supine and upright postures were positioned in a linear fashion on the same stroke volume-MSNA stimulus-response relationship as the average pre-flight stroke volume and MSNA responses. Since all astronauts who participated in the Neurolab orthostatic experiments completed the 10-min tilt table tests, these observations supported the notion that sympathetic reflex responses were not altered but functioned adequately after space flight in non-presyncopal subjects. In contrast to the Neurolab results, development of orthostatic hypotension and presyncopal events reported in astronauts during standing after space flight have been accompanied by attenuated peripheral vasoconstriction and less elevation in plasma concentrations of norepinephrine. The association between circulating norepinephrine (NE) and peripheral vascular resistance in presyncopal astronauts after space flight led to the conclusion that postflight presyncope can be attributed to a combination of inherently low-resistance responses, a strong dependence on volume status, and relative hypoadrenergic function. In the present investigation, we used graded levels of lower body negative pressure (LBNP) to produce linear reductions in stroke volume and performed direct measurements of MSNA to test the hypotheses that (1) elevations in MSNA during central hypovolemia are proportional (i.e., linear) with reductions in stroke volume and; (2) that the slope of the stroke volume-MSNA relationship will be reduced in presyncopal subjects.     

Effect of simulated microgravity on human lymphocytes

During space flight the function of the immune system changes significantly. Several papers reported that postflight the number and the proportion of circulating leukocytes in astronauts are modified (Leach, 1992), the in vitro mitogen induced T cell activation is depressed (Cogoli et al., 1985; Konstantinova et al. 1993) and there are detectable differences in cytokine production of leukocytes as well (Talas et al. 1983; Batkai et al. 1988; Chapes et al. 1992). One of the possible modifying forces is the microgravity condition itself. Our aim was to analyse mechanisms responsible for changing leukocyte functions in low gravity environment. For terrestrial simulation of microgravity we used a Rotary Cell Culture System (RCCS) developed by NASA. We investigated the effect of simulated microgravity on separated human peripheral blood mononuclear cells (PBMCs). We detected the populations of different cells by antibodies conjugated to fluorofors using a Flow Cytometer. Since space flight reduces the number of peripheral blood lymphocytes (Stowe et al., 1999) we supposed that apoptotic (programmed cell death) processes might be involved. This hypothesis was supported by the result of our earlier experiment demonstrating that simulated microgravity increased the level of secreted Tumor Necrosis Factor-alpha (TNFalpha, a known apoptotic signal molecule) significantly (Batkai et al. 1999).     

Recording of blood pressure,heart rate and aortic nerve activity during parabolic flight in the rat via radio-telemetry

Exposure to microgravity induces cardiovascular deconditioning characterized by orthostatic hypotension when astronauts return to the earth. In order to understand the mechanism of cardiovascular deconditioning, it is necessary to clarify the changes in hemodynamics and the cardiovascular regulation system over the period of space flight. The telemetry system applied to freely moving animals will be a useful and appropriate technique for this kind of long term study of the cardiovascular system in the conscious animal during space flight. The purpose of the present study is twofold: firstly, to observe the detailed changes of arterial pressure and heart rate (HR) during microgravity elicited by the parabolic flight in order to study the acute effect of microgravity exposure on the cardiovascular system; and secondly, to test the feasibility of the telemetry system for recording blood pressure, HR and autonomic nervous activities continuously during space flight.     

Autoflora in the upper respiratory tract of Apollo astronauts.

The typical microbial inhabitants of the oral and nasal cavities of Apollo astronauts were identified before space flight and generally found to be similar to those previously reported for healthy male adults. Additional analyses of samples collected immediately after return of the Apollo 13, 14, 15, and 16 crew members to earth were performed to evaluate the effects of space travel on the microbial bioburden of the upper respiratory tract. In-flight cross-contamination and buildup of pathogens such as Staphylococcus aureus were noted, although significant increases in nonpathogenic species were absent. Other proposed alterations, such as dysbacteriosis (flooding of the mouth with a single species) and simplification of the autoflora, did not occur. Generally, the incidence and quantitation of each species after flight was within the preflight range, although the number of viable Haemophilus cells recovered from the mouth decreased significantly after space flight. Except for those minor alterations listed above, the aerobic and anaerobic bacterial components of the upper respiratory autoflora of Apollo astronauts was found to be stable after space flight of up to 295 h.     

Analysis of possible causes of activation of gastric and the pancreatic excretory and incretory function after completion of space flight at the international space station

A comparative analysis of the excretory and incretory activity of the stomach and pancreas in astronauts soon after completion of space flights of various durations was performed. An increase in the fasting activity of gastric and pancreatic enzymes and hormones (insulin and C-peptide) in blood, reflecting the increased excretory and incretory activity of organs of the gastroduodenal region developing in microgravity, was demonstrated. The absence of subjects infected with Helicobacter pylori in the space flight crew excluded the involvement of this microorganism in the mechanism underlying the increase in the gastric secretory activity. The absence of correlation between the increase in the secretory activity of organs of the gastroduodenal region and the duration of the space flight allowed us to rule out the hypokinetic mechanism, which is associated with the duration of exposure to microgravity. It was concluded that the main mechanism underlying the changes in the functional state of the digestive system in space flight may be determined by the rearrangement of the venous hemodynamics of organs of the abdominal cavity, unrelated to the duration of exposure to microgravity. It was shown that, after completion of space flights and in ground-based experiments simulating the hemodynamic rearrangement occurring in microgravity, the increase in the basal excretory activity of gastroduodenal organs was not caused by gastrin secretion and occurred simultaneously with an increase in the secretion of insulin, which is considered as a putative hormonal component of the hemodynamic mechanism.     

Influence of space flight on red blood cells

Losses of red blood cell mass (RCM) averaging 10-15% have been observed consistently in astronauts after space flight; postflight recovery of RCM requires 4-6 wk. Although apparently not harmful to the health and effectiveness of crews during uncomplicated flights, decreased RCM could compromise health and performance in the event of illness, injury, or partial malfunction of the life support system. Whether the loss of RCM would worsen or stabilize in missions longer than 7 months is unknown. As a biological response, it is a significant, predictable reaction whose etiology, biological mechanisms, and potential operational significance are inadequately defined. Weightlessness is probably the primary cause; however, contributory factors may include hypokinesia/hypodynamia, bone loss, muscle atrophy, altered hemodynamics, stress, and metabolic disturbances. Space medical specialists consider other possible influences such as hypoxia, hypobaria, radiation, toxic contaminants, and launch and reentry accelerations as less likely factors. Because the data base on loss of RCM is insufficient for the National Aeronautics and Space Administration's space medical responsibilities, the Life Sciences Research Office ad hoc Working Group on Space Anemia suggested research approaches ranging form fundamental topics such as utilization of erythropoietin and oxygen in target organs and cell-cell interactions, through possible splenic and vascular dysfunctions, metabolic disturbances, and inhibitors of erythropoiesis, to methodology and models.     

Complex chromosomal rearrangements induced in vivo by heavy ions

It has been suggested that the ratio complex/simple exchanges can be used as a biomarker of exposure to high-LET radiation. We tested this hypothesis in vivo, by considering data from several studies that measured complex exchanges in peripheral blood from humans exposed to mixed fields of low- and high-LET radiation. In particular, we studied data from astronauts involved in long-term missions in low-Earth-orbit, and uterus cancer patients treated with accelerated carbon ions. Data from two studies of chromosomal aberrations in astronauts used blood samples obtained before and after space flight, and a third study used blood samples from patients before and after radiotherapy course. Similar methods were used in each study, where lymphocytes were stimulated to grow in vitro, and collected after incubation in either colcemid or calyculin A. Slides were painted with whole-chromosome DNA fluorescent probes (FISH), and complex and simple chromosome exchanges in the painted genome were classified separately. Complex-type exchanges were observed at low frequencies in control subjects, and in our test subjects before the treatment. No statistically significant increase in the yield of complex-type exchanges was induced by the space flight. Radiation therapy induced a high fraction of complex exchanges, but no significant differences could be detected between patients treated with accelerated carbon ions or X-rays. Complex chromosomal rearrangements do not represent a practical biomarker of radiation quality in our test subjects.     

REGULATION OF HAEMOPOIESIS IN ALTERED GRAVITY

(1) The aetiology of one of the most striking physiological changes occurring during space-flight, the loss of red blood cells, remains unknown, and its precise time-pattern in flight has not yet been studied. (2) It is suggested that the changes during space-flight responsible for loss of red blood cells in man are (a) loss of plasma volume resulting from disappearance of hydrostatic pressure in the circulation during weightlessness and (b) reduced energy expended in maintenance of form, posture and locomotion resulting from elimination of the usual gravitational load on the muscles. Quadrupeds, like rats, would be expected to suffer minimal blood shifts in weightlessness and therefore have an unchanged plasma volume. However, since in weightlessness the activity-related energy expenditure by the muscles is reduced, the accompanying reduced oxygen demand by the tissues would cause a reduction in erythropoietin levels and so in the production of red blood cells, and a progressive lowering of the total red blood cell mass toward a new steady-state level. (3) Loss of plasma volume alone does not explain the observed loss of red blood cells in astronauts because, in the three manned Skylab missions, as the duration of the missions increased, loss of red blood cell mass decreased, whereas loss of plasma volume increased. This discrepancy is, however, well accounted for by the above hypothesis by taking into consideration the increased level of exercise of the astronauts as the duration of the mission increased. (4) Though water submersion of human subjects does mimic the effects of weightlessness, such effects were overriden in sea mammals because of adaptation to other factors associated with a life in the sea. (5) From the presented analysis of haemopoietic changes observed in spaceflight, an experiment can be designed for a future flight to uncover the causes and mechanisms of these changes and provide a basis for developing protective measures. Thus, the space environment can be used as an investigative tool to enhance the knowledge of the function of the haemopoietic system, which is a major homeostatic system of man and other vertebrates.     

Effects of a Closed Space Environment on Gene Expression in Hair Follicles of Astronauts in the International Space Station

Adaptation to the space environment can sometimes pose physiological problems to International Space Station (ISS) astronauts after their return to earth. Therefore, it is important to develop healthcare technologies for astronauts. In this study, we examined the feasibility of using hair follicles, a readily obtained sample, to assess gene expression changes in response to spaceflight adaptation. In order to investigate the gene expression changes in human hair follicles during spaceflight, hair follicles of 10 astronauts were analyzed by microarray and real time qPCR analyses. We found that spaceflight alters human hair follicle gene expression. The degree of changes in gene expression was found to vary among individuals. In some astronauts, genes related to hair growth such as FGF18, ANGPTL7 and COMP were upregulated during flight, suggesting that spaceflight inhibits cell proliferation in hair follicles.     

Antibiotic efficacy and microbial virulence during space flight

Human space flight is a complex undertaking that entails numerous technological and biomedical challenges. Engineers and scientists endeavor, to the extent possible, to identify and mitigate the ensuing risks. The potential for an outbreak of an infectious disease in a spacecraft presents one such concern, which is compounded by several components unique to an extraterrestrial environment. Various factors associated with the space flight environment have been shown to potentially compromise the immune system of astronauts, increase microbial proliferation and microflora exchange, alter virulence and decrease antibiotic effectiveness. An acceptable resolution of the above concerns must be achieved to ensure safe and efficient space habitation. To help bring this about, scientists are employing advances in biotechnology to better characterize the relevant variables and establish appropriate solutions. Because many of these clinical concerns are also relevant in terrestrial society, this research will have reciprocal benefits back on Earth.     

Plasma hormone levels in human subject during stress loads in microgravity and at readaptation to Earth's gravity

In great part of the investigations of endocrine system functions in astronauts during space flights the plasma levels of hormones and metabolites were determined only in resting conditions, usually from one blood sample collection. Such levels reflected the psychical and physical state and new hormonal homeostasis of organism at the time of blood collection, however, the functional capacity of neuroendocrine system to respond to various stress stimuli during space flight remained unknown. The aim of present investigations was to study dynamic changes of hormone levels during the stress and metabolic loads (insulin induced hypoglycemia, physical exercise and oral glucose tolerance test) at the exposure of human subject to microgravity on the space station MIR. The responses of sympatico-adrenomedullary system to these stress and workloads were presented by Kvetnansky et al.     

Decreased non-MHC-restricted (CD56+) killer cell cytotoxicity after spaceflight.

Cytotoxic activity of non-major histocompatibility complex-restricted (CD56+) (NMHC) killer cells and cell surface marker expression of peripheral blood mononuclear cells were determined before and after spaceflight. Ten astronauts (9 men, 1 woman) from two space shuttle missions (9- and 10-day duration) participated in the study. Blood samples were collected 10 days before launch, within 3 h after landing, and 3 days after landing. All peripheral blood mononuclear cell preparations were cryopreserved and analyzed simultaneously in a 4-h cytotoxicity (51)Cr release assay using K562 target cells. NMHC killer cell lytic activity was normalized per 1,000 CD56+ cells. When all 10 subjects were considered as one study group, NMHC killer cell numbers did not change significantly during the three sampling periods, but at landing lytic activity had decreased by approximately 40% (P < 0.05) from preflight values. Nine of ten astronauts had decreased lytic activity immediately after flight. NMHC killer cell cytotoxicity of only three astronauts returned toward preflight values by 3 days after landing. Consistent with decreased NMHC killer cell cytotoxicity, urinary cortisol significantly increased after landing compared with preflight levels. Plasma cortisol and ACTH levels at landing were not significantly different from preflight values. No correlation of changes in NMHC killer cell function or hormone levels with factors such as age, gender, mission, or spaceflight experience was found. After landing, expression of the major lymphocyte surface markers (CD3, CD4, CD8, CD14, CD16, CD56), as determined by flow cytometric analysis, did not show any consistent changes from measurements made before flight.     

The water-salt balance and renal function in space flights and in model experiments

Study of a condition of mineral and water-electrolyte metabolism, function of kidneys, and their hormonal regulation during model experiments (hypokinesia, bed rest, immersion etc.), and also in space flights and in readaptation period, has shown a major role of water-electrolyte homeostasis during general adaptation of humans and animals to new conditions of life and to conditions of weightlessness in particular. The change in regulation of volumes of fluid milieu in an initial period of weightlessness was shown to be the consequence of redistribution of blood and hemodynamics of the shifts resulting in change of production of volume-regulation hormones, formation of negative water balance, and redistribution of fluid in the organism among various fluid compartments. At later stages of flight or long-term hypokinesia, a change of water-electrolyte homeostasis occurs with a decrease in the kidneys excretion of sodium, and diuresis, but with an increased excretion of calcium and production of ADH and RAAS hormones. Following returning to earth gravitation, the majority of astronauts have adaptive reactions, compensating for the loss extracellular fluid and mineral substances and formation of "earth" water-electrolyte homeostasis. For estimation of water-electrolyte homeostasis and the functions of kidneys in astronauts, various functional loading tests have been developed. The developed system of preventive maintenance is successfully used for abolition of adverse changes at various stages of space flight and in readaptation period.