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.     

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.     

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.     

Russian system of countermeasures on board of the International Space Station (ISS): the first results

The system of countermeasures used by Russian cosmonauts in space flights on board of International Space Station (ISS) was based on the developed and tested in flights on board of Russian space stations. It included as primary components: physical methods aimed to maintain the distribution of fluids at levels close to those experienced on Earth; physical exercises and loading suits aimed to load the musculoskeletal and the cardiovascular systems; measures that prevent the loss of fluids, mainly, water-salt additives which aid to maintain orthostatic tolerance and endurance to gravitational overloads during the return to Earth; well-balanced diet and medications directed to correct possible negative reactions of the body to weightlessness. Fulfillment of countermeasure's protocols inflight was thoroughly controlled. Efficacy of countermeasures used were assessed both in- and postflight. The results of studies showed that degrees of alterations recorded in different physiological systems after ISS space flights in Russian cosmonauts were significantly higher than those recorded after flights on the Russian space stations. This phenomenon was caused by the failure of the ISS crews to execute fully the prescribed countermeasures' protocols which was as a rule excused by technical imperfectness of exercise facilities, treadmill TVIS particularly.     

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.     

Exercise response to simulated weightlessness

Two bed rest analog studies of space flight were performed; one 14 d and the other 28 d in duration. Exercise response was studied in detail during the 28 d study and following both the 14 d and 28 d studies. This paper relates the results of these studies to physiologic changes noted during and following space flight. The most consistent change noted after both bed rest and space flight is an elevated heart rate during exercise. A second consistent finding is a postflight or postbed rest reduction in cardiac stroke volume. Cardiac output changes were variable. The inability to simulate inflight activity levels and personal exercise makes a direct comparison between bed rest and the results from specific space flights difficult.     

Study of water-salt metabolism and renal function in cosmonauts

In manned space flights the renal function and water-salt metabolism undergo substantial changes. With the reserve capabilities of kidneys in mind, their function and regulation of the water-salt balance were investigated in cosmonauts postflight and in Earth-bound simulation experiments with the aid of water loading, hormonal injections (pituitrin, engiotensin, DOCA, ACTH); water- and ion-release were also studied during LBNP and physical exercises. The cosmonauts who performed space flights of 2 to 5 days showed water retention and increased urine excretion of salts during the first postflight days in response to a water load. After the 18-day flight water excretion remained unchanged whereas salt excretion increased. The capacity for osmotic concentration and urine dilution did not alter. The study of the hormonal effect in simulation experiments of different duration demonstrated a normal renal response to the hormonal excretion. After the LBNP tests and physical exercises the water- and salt-excretion declined; a correlation between the level of water- and salt-excretion and the level of these loads was established. The data on the blood- and urine-ionic composition, excretion of nitrogen metabolites, and hormones postflight as well as the results of load and functional tests suggest that changes in the renal function of cosmonauts in weightlessness are associated with regulatory effects on the kidney rather than disturbances in the function of nephron cells.     

Bone effects of space flight: analysis by quantum concept of bone remodelling.

During the manned Skylab flights mineral losses from the calcaneum and changes in external calcium balance were in the ranges found for healthy subjects at bedrest. Calcium balance reached a nadir of -200 mg/day by two months with no change thereafter; the negative balance was due to increased urinary excretion with no change in net absorption. The total calcium loss averaged 18 g in the longest flight of 84 days; the densitiometric data suggested that about two-thirds of this came from trabecular bone and about one-third from cortical bone. These data could represent reversible bone loss due to increased birth rate of normal osteoclasts and osteoblasts and consequent increase in bone turnover and in reversible mineral deficit, or irreversible bone loss due to overactive osteoclasts and/or underactive osteoblasts. If the former explanation is correct, significant bone loss is unlikely whatever the duration of future flights, except in older persons already losing bone; if the latter explanation is correct, space flights longer than six months may lead to a significant increase in fracture risk in later life. Neither terrestrial immobilization nor unwilling animals in orbit are ideal models for the effects of space flight on human bone. To choose between reversible and irreversible mechanisms of bone loss, and to determine the effects of space flight on lifelong fracture risk, future astronauts and cosmonauts must undergo adequate histologic study of bone after in vivo tetracycline labeling.     

Autonomic function testing aboard the ISS using “PNEUMOCARD”

Investigations of blood pressure, heart rate (HR), and heart rate variability (HRV) during long term space flights on board the “ISS” have shown characteristic changes of autonomic cardiovascular control. Therefore, alterations of the autonomic nervous system occurring during spaceflight may be responsible for in- and post-flight disturbances. The device “Pneumocard” was developed to further investigate autonomic cardiovascular and respiratory function aboard the ISS. The hard-software diagnostic complex “Pneumocard” was used during in-flight experiment aboard ISS for autonomic function testing. ECG, photoplethysmography, respiration, transthoracic bioimpedance and seismocardiography were assessed in one male cosmonaut (flight lengths six month). Recordings were made prior to the flight, late during flight, and post-flight during spontaneous respiration and controlled respiration at different rates.HR remained stable during flight. The values were comparable to supine measurements on earth. Respiratory frequency and blood pressure decreased during flight. Post flight HR and BP values increased compared to in-flight data exceeding pre-flight values. Cardiac time intervals did not change dramatically during flight. Pulse wave transit time decreased during flight. The maximum of the first time derivative of the impedance cardiogram, which is highly correlated with stroke volume was not reduced in-flight.Our results demonstrate that autonomic function testing aboard the ISS using “Pneumocard” is feasible and generates data of good quality. Despite the decrease in BP, pulse wave transit time was found reduced in space as shown earlier. However, cardiac output did not decrease profoundly in the investigated cosmonaut.Autonomic testing during space flight detects individual changes in cardiovascular control and may add important information to standard medical control. The recent plans to support a flight to Mars, makes these kinds of observations all the more relevant and compelling.     

Life-sciences research opportunities in commercial suborbital space flight

Commercial suborbital space flights will reach altitudes above 100 km, with 3–5 min of weightlessness bracketed by high-g launch and landing phases. The proposed frequency of these flights, and the large passenger population, present interesting opportunities for researchers in the life sciences. The characteristics of suborbital flight are between those of parabolic and orbital flights, opening up new scientific possibilities and easing the burden for obtaining access to 0g.     

Pharmacological approaches

The use of drugs as countermeasures in the United States and Russian space programs is examined. Pharmacological tools for short and extended space flights are reviewed. Medications flown on the Shuttle are listed. Considerations for the use of pharmacological countermeasures include pharmacokinetics and pharmacodynamics, drug interactions, therapeutic interventions, space motion sickness, the musculoskeletal system, radiation protection, space flight anemia, and cardiovascular disorders.     

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.     

Spacelab Life Sciences flight experiments: an integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO2 and C2H2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be obtained. The central venous catheter will be inserted immediately pre-launch and monitored with heart rate and blood pressure in-flight until cardiac output, respiratory gas exchange and quantitative 2D echocardiography measurements can be performed. In-flight hemodynamic measurements will be repeated at rest and during submaximal exercise daily and also during maximal exercise midway through the flight to document the timecourse and extent of cardiovascular changes in the payload crew. Parallel studies are planned for the animals. In addition to measurements of right atrial and aortic pressures and cardiac output, a dorsal micro-circulatory chamber will allow determinations of changes in capillary and venular architecture and function in six of the rats. The techniques and findings from many of the SLS-1 and 2 supporting studies have already yielded significant information about circulatory regulation in patients with both hypo- and hypertension. The flight experiments themselves will provide new data to test the validity of both animal and human models currently used for simulating the fluid shifts of a micro-gravity environment. The development of effective countermeasures, not only for short and long duration space travellers, but also for Earth-bound medical patients can then be physiologically based on experimental data rather than anecdote.     

Sleep in space

Manned space flights have shown it is possible to sleep in microgravity. However, some sleep disturbances have been reported which influence performance of the crew and safety of space flight. This paper reviews the main studies of in-flight sleep in animal and man. Most disturbances are related to phase lags due to operational requirements. Factors which can disturb in-flight sleep are analysed: environmental factors. Some of them are secondary to space flight ergonomics. Conversely, effects of microgravity on light-dark alternance are less known and lead to interesting problems of fundamental research, psychological factors, especially during long duration flights.     

Recent results of the joint ESA-DARA/IBMP experiments Biokosmos "Seeds"

Comparison of experimental data obtained from short (SDEF) and long duration exposure flights (LDEF) have recently led to results which will be significant for longer and/or repeated sojourn of man in space. Under orbital conditions biological stress and damage are induced in test subjects by cosmic radiation, especially the high energetic, densely ionizing component of heavy ions. Plant seeds were successful model systems for a biotest in studying the physiological damages and mutagenic effect caused by ionizing cosmic radiation in particular stem cells. Dosimetrically, the subdivision into charge- and Let-groups reveals the contribution of the intermediate group (LET = 350-1000 MeV/cm) due to the medium heavy ions (Z = 6-10). Their relative contribution increases with the lower inclination of the orbit of LDEF-1; on the other hand, the total fluence becomes higher with longer duration of the flight. The observed endpoints of the biological radiation damage hint at a correlation with particle dose rate rather than with the dose; additionally, data on shielding effects inside and outside the space craft and its exposure were gained from the different SDEF- and LDEF-missions.     

Long-term biological investigations in space

Missions in space within the next two decades will be of longer duration than those carried out up to the present time, and the effects of such long-term flights on biological organisms are unknown. Results of biological experiments that have been performed to date cannot be extrapolated to results in future flights because of the unknown influence of adaptation over a long period of time. Prior experiments with Axolotl, fishes, and vertebrates by our research team (in part with sounding rockets) showed that these specimens did not appear to be suitable for long-term missions on which minimization of expense, technique, and energy is required. Subsequent investigations have shown the suitability of the leech (Hirudo medicinalis), which consumes blood of mammals up to ten times its own weight (1 g) and can live more than 2 years without further food supply. Emphasis in the experiments with Hirudo medicinalis is placed on metabolic rhythm and motility. Resorption and diffusion in tissue, development, and growth under long-term effects of cosmic proton radiation and zero-gravity are other focal points. The constancy of cellular life in the mature animals is a point in favor of these specimens. We have also taken into account the synergistic effects of the space environment on the problems just mentioned. The life-support system constructed for the leech has been tested successfully in four sounding rocket flights and, on that basis, has been prepared for a long-term mission. Long-term investigations out of the terrestrial biosphere will provide us with information concerning the degree of adaptation of certain physiological and biochemical functions and as to what extent biological readjustment or repair processes can occur under the specific stress conditions of space flight.     

Mass-, time-, and energy-characteristics of the interstellar flights during the long proper time of astronauts

The existence of extraterrestrial intelligence (ETI) and extraterrestrial scientific-technical civilization (STC) is of principal importance for CETI (communication with extraterrestrial intelligence) and SETI (search for extraterrestrial intelligence). According to Kardashev and Bracewell, the Earth-like STC in their farther development can expand to the nearby planetary systems of the Galaxy, creating galactic community (Bracewell's galactic club).In a previous paper the possibilities of the one-step relativistic rocket interstellar flight during the proper time of life of one-two generations of astronauts were analysed. The realization of such interstellar flights is very improbable, even to the nearest stars. These results could be true for the case of the comparatively short proper time of astronauts, i.e. large acceleration. But flights to the nearest stars could be realized with small and very small accelerations. In the present paper are calculated the proper times t in the reference systems connected with the astronauts (S₂), as well as the times T in the reference systems (S₁)-inertial, velocities v in S₁, mass ratios, powers and energies for various flights, exhaust velocities u and accelerations a. Results are critically discussed.     

Cardiovascular system and microgravity simulation and inflight results.

Main results of cardiovascular investigation, performed with ultrasound methods during the common French/Soviet flight aboard Salyut VII in June 1982, are compared to variations of the same parameters studied during ground-based simulations on the same subject or observed by other investigators during various ground-based experiences. The antiorthostatic bed rest simulation partly reproduces microgravity conditions and seems to be better adaptated to cardiac hemodynamics, despite some differences, and to the cerebral circulation, than to the inferior limb circulation.     

Summary of medical investigations in the U.S.S.R. manned space missions.

The results of biomedical investigations carried out in the U.S.S.R. manned space missions are discussed. Their basic result is well-documented evidence that man can perform space flights of long duration. The investigations have demonstrated no direct correlation between inflight or postflight physiological reactions of crewmembers and flight duration. In all likelihood, this can be attributed to the fact that special exercises done inflight efficiently prevented adverse effects of weightlessness. However, human reactions to weightlessness need further study. They include negative calcium balance and anemia as well as vestibulo-autonomic disorders shown by crewmembers at early stages of weightlessness. Attention should be given to psychological, social-psychological and ethical problems that may also limit further increase in flight duration.     

T cell regulation in microgravity – The current knowledge from in vitro experiments conducted in space,parabolic flights and ground-based facilities

Dating back to the Apollo and Skylab missions, it has been reported that astronauts suffered from bacterial and viral infections during space flight or after returning to Earth. Blood analyses revealed strongly reduced capability of human lymphocytes to become active upon mitogenic stimulation. Since then, a large number of in vitro studies on human immune cells have been conducted in space, in parabolic flights, and in ground-based facilities. It became obvious that microgravity affects cell morphology and important cellular functions. Observed changes include cell proliferation, the cytoskeleton, signal transduction and gene expression. This review gives an overview of the current knowledge of T cell regulation under altered gravity conditions obtained by in vitro studies with special emphasis on the cell culture conditions used. We propose that future in vitro experiments should follow rigorous standardized cell culture conditions, which allows better comparison of the results obtained in different flight- and ground-based experiment platforms.