Medical problems of manned space flights onboard orbital stations.

Medical aspects of crew safety and life support as well as biomedical investigations form part and parcel of the preparation and conduct of manned space programs. The list of biomedical problems related to these programs is very long. The present paper concentrates on some of them.     

Main medical results of extended flights on space station Mir in 1986-1990

During 1986-1990 seven prime spacecrews (16 cosmonauts) have flown on-board the Mir orbital complex. The longest space mission duration was 366 days The principal objectives of the medical tasks were the maintenance of good health and performance of the spacecrews and conducting medical research programs which included study of the cardiovascular, motor, endocrine, blood, immune, and metabolic systems. Results obtained point to the ability of humans to readily adapt to a year-long stay in space and maintain good health and performance. Readaptation had a similar course as after other previous long-term space flights of up to 8 months in duration. Primary body system changes were not qualitatively different from findings after flights aboard the Salyut 6 and 7 space stations. In this case, during and after an 11-12 month flight, body system alterations were even less severe which was a result of adequate countermeasure use, their systematic and creative employment and maintenance of required environments to support life and work in space.     

Radiation danger in prolonged manned space flights

The author examines methods for prognosticating solar activity for several decades to determine optimum periods for prolonged space flight. The focus of the discussion is the presence of a change in magnetic polarity at the beginning of each 11-year solar cycle, resulting in a 22-year cycle. An historical review of solar cycles determined a super cycle of about 180 years. Using this data, it is determined that solar activity will be weak through the end of the 20th century.     

Central and regional hemodynamics in prolonged space flights.

This paper presents the results of measuring central and regional (head, forearm, calf) hemodynamics at rest and during provocative tests by the method of tetrapolar rheography in the course of Salyut-6-Soyuz and Salyut-7-Soyuz missions. The measurements were carried out during short-term (19 man-flights of 7 days in duration) and long-term (21 man-flights of 65-237 days in duration) manned missions. At rest, stroke volume (SV) and cardiac output (CO) as well as heart rate (HR) decreased insignificantly (in short-term flights) or remained essentially unchanged (in long-term flights). In prolonged flights CO increased significantly in response to exercise tests due to an increase in HR and the lack of changes in SV. After exercise tests SV and CO decreased as compared to the preflight level. During lower body negative pressure (LBNP) tests HR and CO were slightly higher than preflight. Changes in regional hemodynamics included a distinct decrease of pulse blood filling (PBF) of the calf, a reduction of the tone of large vessels of the calf and small vessels of the forearm. Head examination (in the region of the internal carotid artery) showed a decrease of PBF of the left hemisphere (during flight months 2-8) and a distinct decline of the tone of small vessels, mainly, in the right hemisphere. During LBNP tests the tone of pre- and postcapillary vessels of the brain returned to normal while PBF of the right and left hemisphere vessels declined. It has been shown that regional circulation variations depend on the area examined and are induced by a rearrangement of total hemodynamics of the human body in microgravity. This paper reviews the data concerning changes in central and regional circulation of men in space flights of different duration.     

Pathophysiology of motor functions in prolonged manned space flights.

The influence of weightlessness on different parts of the motor system have been studied in crew members of 140 and 175 days space flights. It has been shown that weightlessness affects all parts of the motor system including (i) the leg and trunk muscles, in which severe atonia, a decrease of strength and an increase of electromyographic cost of contraction have been observed, (ii) the proprioceptive elements and the spinal reflex mechanisms in which decreased thresholds accompanied by decreases of maximal amplitude of reflexes and disturbances in cross reflex mechanisms have been found. and (iii) the central mechanisms that control characteristics of postural and locomotor activities. The intensities and durations of disturbances of different parts of the motor system did not correlate to each other, but did correlate with prophylactic activity during space flight. The data suggest a different nature of disturbances caused by weightlessness in different parts of the motor system.     

Biomedical problems of EVA support during manned space flight to Mars

Current projects of manned missions to Mars are aimed to their realization in the second-third decades of this century. The purpose of this paper is to determine and review the main biomedical problems, that require a first and foremost decision for safety support of extravehicular activity (EVA) carried out by crewmembers of the Mars expedition. To a number of such problems the authors of the paper attribute a creation of adequate EVA equipment intended, first, for assembly of interplanetary spacecraft on the Earth orbit, performance of maintenance operations and scientific researches on the external surface of spacecraft during interplanetary flight and, secondly, for work on the Mars surface. New generation of space suits with low weight, high mobility and acceptable risk of decompression sickness must be as a central component of EVA equipment. The program for preparation to a Mars expedition also has to include special investigations in order to design the means and methods for a reliable protection of crew against space radiation, to elaborate the approach to medical monitoring and primary medical care during autonomous space mission, to maintain good health condition of crewmembers during EVA under the Mars gravity (0.38 g) after super long-term flight in weightlessness.     

T-cell immunity and cytokine production in cosmonauts after long-duration space flights

Long-duration spaceflight effects on T-cell immunity and cytokine production were studied in 12 Russian cosmonauts flown onto the International Space Station. Specific assays were performed before launch and after landing and included analysis of peripheral leukocyte distribution, analysis of T-cell phenotype, expression of activation markers, apoptosis, proliferation of T cells in response to a mitogen, concentrations of cytokines in supernatants of cell cultures. Statistically significant increase was observed in leukocytes’, lymphocytes’, monocytes’ and granulocytes’ total number, increase in percentage and absolutely number of CD3⁺CD4⁺-cells, CD4⁺CD45RA⁺-cells and CD4⁺CD45RA⁺/CD4⁺CD45RО⁺ ratio, CD4⁺CD25^+Bright regulatory cells (p<0,05) in peripheral blood after landing. T-lymphocytes’ capacity to present CD69 and CD25 on its own surfaces was increased for the majority of crewmembers. Analysis of T-cell response to PHA-stimulation in vitro revealed there were some trends toward reduced proliferation of stimulated T-lymphocytes. There was an apparent post flight decrease in secreted IFN-g for the majority of crewmembers and in most instances there was elevation in secreted IL-10. It revealed depression of IFN-g/IL-10 ratio after flight. Correlation analysis according to Spearman’s rank correlation test established significant positive correlations (p<0.05) between cytokine production and T-cell activation (CD25+, CD38+) and negative correlation (p<0.05) between cytokine production and number of bulk memory CD4+T-cells (CD45RO+). Thus, these results suggest that T-cell dysfunction can be conditioned by cytokine dysbalance and could lead to development of disease after long-duration space flights.     

Oxygen regimen in the human peripheral tissue during space flights.

A survey of the results of the experiment "Oxygen," carried out within the scope of the INTER-KOSMOS program in members of the permanent crews and of international visiting expeditions to the Soviet orbital station Salyut-6, is given. During the 7-day space flights of the international visiting expeditions a significant decrease in pO2ic by 3.28 kPa was observed. Local oxygen utilization reduced significantly by 0.44 kPa. During hyperventilation testing after return to earth a statistically significant decrease in the peak value by 1.39 kPa was noted. In the long-term crews of the orbital station Salyut-6 the highest decrease in pO2ic of 3.8 kPa and the absolutely lowest value of 3.4 -/+ 0.5 kPa during space flight were observed. The decrease in local oxygen utilization during the flight of 0.8 kPa/min was greater than that of the visiting crews. The results indicate the importance of investigating the dynamics of the oxygen regimen for medical control of the crew members both during the space flight and during the readaptation phase after return to earth.     

The dynamics of blood biochemical parameters in cosmonauts during long-term space flights

Most of the previously obtained data on cosmonauts' metabolic state concerned certain stages of the postflight period. In this connection, all conclusions, as to metabolism peculiarities during the space flight, were to a large extent probabilistic. The purpose of this work was study of metabolism characteristics in cosmonauts directly during long-term space flights. In the capillary blood samples taken from a finger, by "Reflotron IV" biochemical analyzer, "Boehringer Mannheim" GmbH, Germany, adapted to weightlessness environments, the activity of GOT, GPT, CK, gamma-GT, total and pancreatic amylase, as well as concentration of hemoglobin, glucose, total bilirubin, uric acid, urea, creatinine, total, HDL- and LDL cholesterol, triglycerides had been determined. HDL/LDL-cholesterol ratio also was computed. The crewmembers of 6 main missions to the "Mir" orbital station, a total of 17 cosmonauts, were examined. Biochemical tests were carried out 30-60 days before launch, and in the flights different stages between the 25-th and the 423-rd days of flights. In cosmonauts during space flight had been found tendency to increase, in compare with basal level, GOT, GPT, total amylase activity, glucose and total cholesterol concentration, and tendency to decrease of CK activity, hemoglobin, HDL-cholesterol concentration, and HDL/LDL - cholesterol ratio. Some definite trends in variations of other determined biochemical parameters had not been found. The same trends of mentioned biochemical parameters alterations observed in majority of tested cosmonauts, allows to suppose existence of connection between noted metabolic alterations with influence of space flight conditions upon cosmonaut's body. Variations of other studied blood biochemical parameters depends on, probably, pure individual causes.     

Ion regulatory function of the human kidney in prolonged space flights.

Ten cosmonauts, who performed 30-175-day space flights aboard Salyut-4 and Salyut-6, and over 60 test subjects who were exposed to bed rest of up to 182 days and immersion of up to 56 days, were examined. The renal excretion of potassium and calcium increased, reaching a maximum by the 4-6th weeks in prolonged space flights and simulation studies. During the load tests with potassium and calcium salt, excretion postflight was much higher than preflight. During potassium chloride load tests a positive correlation between the blood content of aldosterone and potassium excretion existed, whereas during calcium lactate load tests an increased calcium excretion was accompanied by a decrease in blood parathyroid hormone concentration. The most probable cause of the negative ion balance in weightlessness is the reduced capacity of tissues to retain electrolytes due to the decreased ion pool capacity. Different exercises have been shown to exert a beneficial effect on electrolyte metabolism.     

Radiobiological risk and single event effects during manned space flights

Radiation hazard during previous manned space flights was not a critical problem as seen from monitoring on board MIR and the SHUTTLE. Future Martian and Lunar missions as well as flights on inclined or high altitude orbits around the Earth can be exposed to a large radiobiological risk and critical reliability losses can be expected, due to Single Event Effects on VLSI devices.

The mains characteristics of these hazards and some counter-measures to be provided for are given.     

Changes in urine protein composition in human organism during long term space flights

The urine protein composition samples of six Russian cosmonauts (male, aged 35–51) who performed long flight missions that varied from 169 to 199 days on the International Space Station (ISS) were analyzed using chromate-mass-spectrometric analysis. The direct shaping of samples was carried out with preliminary cleaning and the protein concentration from experiment participants urine was determined with the aid of MB-HIC C8 (“Bruker Daltonics”) magnetic particles set with the subsequent MALDI-TOF mass-spectrometric analysis on Autoflex III TOF/TOF (Bruker Daltonics) mass spectrometer operating in the positive linear mode. Also, the analysis of samples with the use of the method of precise mass markers and their elution time from the chromatographic column was done as well as further identification of proteins by MS–MS peptide spectrum based on the Mascot search system. The results of the implemented research made it possible to obtain new data necessary for genesis changes clarifying those which occur in the human organism under the action space flight factors.     

Biomedical support of man in space

In its broadest sense, biomedical support of man in space must not be limited to assisting spacecraft crew during the mission; such support should also ensure that flight personnel be able to perform properly during landing and after leaving the craft. Man has developed mechanisms that allow him to cope with specific stresses in his normal habitat; there is indisputable evidence that, in some cases, the space environment, by relieving these stresses, has also allowed the adaptive mechanisms to lapse, causing serious problems after re-entry. Inflight biomedical support must therefore include means to simulate some of the normal stresses of the Earth environment. In the area of cardiovascular performance, we have come to rely heavily on complex feedback mechanisms to cope with two stresses, often combined: postural changes, which alter the body axis along which gravitational acceleration acts, and physical exercise, which increases the total load on the system. Unless the appropriate responses are reinforced continuously during flight, crew members may be incapacitated upon return. The first step in the support process must be a study of the way in which changes in g, even of short duration, affect these responses. In particular we should learn more about effects of g on the "on" and "off" dynamics, using a variety of approaches: increased acceleration on one hand at recumbency, immersion, lower body positive pressure, and other means of simulating some of the effects of low g, on the other. Once we understand this, we will have to determine the minimal exposure dose required to maintain the response mechanisms. Finally, we shall have to design stresses that simulate Earth environment and can be imposed in the space vehicle. Some of the information is already at hand; we know that several aspects of the response to exercise are affected by posture. Results from a current series of studies on the kinetics of tilt and on the dynamics of readjustment to exercise in different postures will be presented and discussed.     

Effects of space flights on human allergic status (IgE-mediated sensitivity)

Suppression of the immune system after space flights of different duration has been reported earlier by Konstantinova [Immune system in extreme conditions, Space immunology. B. 59. M. Science 1988. 289p. (in Russian) [4]; Immunoresistance of man in space flight, Acta Astronautica 23 (1991) 123–127 [5]]. Changes in T- and B-mediated activities of the immune system were demonstrated during and after space flight. However, the influence of the space flight conditions on the allergic status of cosmonauts and astronauts is still unclear. The goal of this investigation was to analyze total blood IgE levels, specific IgE-antibodies and interleukin-4 in blood of Russian crew members before and after space flights to the International Space Station (ISS) and during a long-term isolation study. For this purpose, we used the ELISA assays as well as other special kits. It was noticed that four out of nine cosmonauts had high total serum IgE (more than normal clinical values of 120 IU/ml). At the same time, there were no statistically significant changes in serum IgE levels before and after long-term space flights (128–195 days). A similar situation was observed regarding preflight IgE levels of cosmonauts who performed short-term flights (7–11 days). However, seven out of 11 cosmonauts had increased IgE level in blood post short flights as compared with pre-flight values. We also measured specific IgE-antibodies, because their high concentration may cause the increased production of total IgE indicating sensitization of cosmonauts. This becomes more important when humans spend a longer time in the closed environment of a space vehicle. Also our ground-based investigations showed that a stay in such conditions does not enhance sensitization to allergens (total number of tested allergens 27) including food, inhalants and cross-reactive proteins. Serum interleukin-4 level measured after short- and long-term space flights was identical. A linear correlation between levels of immunoglobulin E and interleukin-4 also was not significant. Despite the fact that our investigations did not establish any influence of space flight on sensitization and development of immediate-type allergic reactions, they demonstrated the necessity to control the allergic status of cosmonauts very carefully both before and after space flights. At the same time, it is necessary to pay special attention to outcomes of atopic individuals with high pre-flight level of total blood IgE.     

Countermeasure of the negative effects of weightlessness on physical systems in long-term space flights

The system of countermcasure of microgravity effects has been developed in Russia that allowed to perform safely long-term space flights. This system that includes different means and methods such as special regimens of physical exercises, axial loading (“Pingiun”) and antigravity suits, low body negative pressure device (LBNP, “Chibis”) and “cuffs” and others has been used with certain variations at certain stages of flight in 27 successfully accomplished space flights that lasted from 60 to 439 days. The pre-, in- and postflight studies performed in 57 crew members of these flights have shown that the system of countermeasure is effective in preventing or diminishing to a great extent almost all the negative effects of weightlessness in flights of a year and more duration and that the intensity and duration of changes recorded in different body systems after flights do not correlate significantly to flight durations, correlating strongly to the volume and intensity of physical exercises used during flight and especially during concluding stage of it.     

MEDES clinical research facility as a tool to prepare ISSA space flights

This new multi-disciplinary medical experimentation center provides the ideal scientific, medical and technical environment required for research programs and to prepare international space station Alpha (ISSA) missions, where space and healthcare industries can share their expertise. Different models are available to simulate space flight effects (bed-rest, confinement,...). This is of particular interest for research in Human psychology, physiology, physiopathology and ergonomics, validation of biomedical materials and procedures, testing of drugs, and other healthcare related products. This clinical research facility (CRF) provides valuable services in various fields of Human research requiring healthy volunteers. CRF is widely accessible to national and international, scientific, medical and industrial organisations. Furthermore, users have at their disposal the multi-disciplinary skills of MEDES staff and all MEDES partners on a single site.     

Trends in space life support.

Considerable progress has been made in recent years on development of candidate physico-chemical components for use in regenerative life support systems (LSS) for future extended-duration-mission spacecraft; these life support systems provide air revitalization including carbon dioxide reduction, water reclamation, and limited waste management. For still longer duration manned space flights, such as a permanently inhabited space station, it is generally recognized that development of biological life support systems capable of generating food and regenerating wastes will be essential to reduce logistics costs.     

Physiological problems for man in space

This article discusses some of the problems facing man in space. Many of these problems are manifested only on return to Earth when the de-conditioned body again has to withstand the effects of gravity.     

Food for thought--nutritional problems in space

The present paper discusses how the study of nutritional problems in space have proceeded, the way microgravity may alter nutritional requirements and how these may be met during long term missions in space.     

Proposal for a new radiation dose control system for future manned space flights

Radiation risk on a future long-duration manned space mission appears to be one of the basic factors in planning and designing the mission. Since 1988 different active dosimetric investigations has been performed on board the MIR space station by the Bulgarian-Russian dosimeter-radiometer LIULIN and French tissue-equivalent proportional counters CIRCE and NAUSICAA. A joint French-Bulgarian-Russian dosimetry experiment and the dosimetry-radiometry system RADIUS-MD have been developed for the future MARS-96 mission. On the base of the results and experience of these investigations a conception for a new radiation dose control system for the future orbital stations, lunar bases and interplanetary space ships is proposed. The proposed system which consists of different instruments will allow personal radiation control for crew members, radiation monitoring inside and outside each habitat, analysis and forecasting of the situation and will suggest procedures to minimize the radiation risk.