Mineral and nitrogen balance study: results of metabolic observations on Skylab II 28-day orbital mission

Prediction that the various stresses of flight, particularly weightlessness, would bring about significant derangements in the metabolism of the musculoskeletal system has been based on various observations of long-term immobilized or inactive bed rest. The only attempt at controlled measurement of metabolic changes in space prior to Skylab, a study during the 14-day Gemini VII flight, revealed rather modest losses of important elements. The three astronauts of Skylab II consumed a planned day-by-day, quite constant, dietary intake of major metabolic elements in mixed foods and beverages and provided virtually complete collections of excreta for 31 days preflight, during the 28 days inflight, and for 17 days postflight. Analyses showed that, in varying degree among the crewmen, urinary calcium increased gradually during flight in a pattern similar to that observed in bed-rest studies: the mean plateau peak of urinary calcium excretion in the latter part of flight was double preflight levels. Fecal calcium excretion did not change significantly, but calcium balance, owing to the urinary calcium rise, became either negative or less positive than in preflight measurement. Increased excretion and negative balance of nitrogen and phosphorus indicated appreciable loss of muscle tissue in all three crewmen. Significant losses also occurred inflight in potassium, sodium, and magnesium. Based on the similarity in pattern and degree between these observations and those in bed rest of the losses in calcium, phosphorus, and nitrogen, musculoskeletal integrity would not be threatened in space flights of up to at least 3 months. However, if similar changes occur, indicative of continuing losses of these elements, in the planned Skylab flights for considerably more than 28 days, concern for capable musculoskeletal function should be serious for flights of very many months' duration, and greater research attention will need to be given to development of protective counter-measures.     

Response and adaptation of bone cells to simulated microgravity

Bone loss induced by microgravity during space flight is one of the most deleterious factors on astronaut’s health and is mainly attributed to an unbalance in the process of bone remodeling. Studies from the space microgravity have demonstrated that the disruption of bone remodeling is associated with the changes of four main functional bone cells, including osteoblast, osteoclast, osteocyte, and mesenchymal stem cells. For the limited availability, expensive costs and confined experiment conditions for conducting space microgravity studies, the mechanism of bone cells response and adaptation to microgravity is still unclear. Therefore, some ground-based simulated microgravity methods have been developed to investigate the bioeffects of microgravity and the mechanisms. Here, based on our studies and others, we review how bone cells (osteoblasts, osteoclasts, osteocytes and mesenchymal stem cells) respond and adapt to simulated microgravity.     

Bone and body mass changes during space flight

Long duration space flight has shown us that humans have significant bone loss and mineral changes because they are living in microgravity. Skylab and the longer Salyut and Mir missions, are providing us useful data and allowing us to explore the mechanism involved in skeletal turnover. Bone redistribution occurs throughout space flight with bone loss predominately in the weight bearing bones of posture and locomotion. The primary health hazards which may occur during space flight induced by skeletal changes include signs and symptoms of hypercalcemia, and the risk of kidney stones and metastatic calcification. After flight lengthy recovery of bone mass and the possible increase in the risk of bone fracture should be considered. Continued research studies are being directed toward determining the mechanisms by which bone is lost in space and developing more effective countermeasures by both the US (Schneider and McDonald, 1984 and Schneider, LeBlanc & Huntoon, 1993) and Russian (Grigoriev et. al., 1989) space programs.     

Medical considerations for extending human presence in space

The prospects for extending the length of time that humans can safely remain in space depend partly on resolution of a number of medical issues. Physiologic effects of weightlessness that may affect health during flight include loss of body fluid, functional alterations in the cardiovascular system, loss of red blood cells and bone mineral, compromised immune system function, and neurosensory disturbances. Some of the physiologic adaptations to weightlessness contribute to difficulties with readaptation to Earth's gravity. These include cardiovascular deconditioning and loss of body fluids and electrolytes; red blood cell mass; muscle mass, strength, and endurance; and bone mineral. Potentially harmful factors in space flight that are not related to weightlessness include radiation, altered circadian rhythms and rest/work cycles, and the closed, isolated environment of the spacecraft. There is no evidence that space flight has long-term effects on humans, except that bone mass lost during flight may not be replaced, and radiation damage is cumulative. However, the number of people who have spent several months or longer in space is still small. Only carefully-planned experiments in space preceded by thorough ground-based studies can provide the information needed to increase the amount of time humans can safely spend in space.     

Prolonged weightlessness and calcium loss in man

Data have been accumulated from a series of studies in which men have been subjected to weightlessness in orbital space flight for periods of up to 12 weeks. These data are used to predict the long term consequences of weightlessness upon the skeletal system. Space flight induced a loss of calcium which accelerated exponentially from about 50 mg/d at the end of 1 week to approx. 300 mg/d at the end of 12 weeks. The hypercalciuria reached a constant level within 4 weeks while fecal calcium losses continued to increase throughout the period of exposure. This apparent diminution of gastrointestinal absorptive efficiency was accompanied by a slight decline in the plasma level of parathyroid hormone and a slight elevation in the plasma level of calcium and phosphorus. Although losses in mineral from the calcaneus were closely correlated with the calcium imbalance, no changes were detected in the mineral mass of the ulna and radius. From the data presented it is concluded that the process of demineralization observed in space flight is more severe than would be predicted on the basis of observations in immobilized, bed rested, or paralyzed subjects. It is, moreover, suggested that the process may not be totally reversible.     

Amino aciduria in weightlessness

Urinary excretion of amino acids by the 9 Skylab crewmen was studied as an indicator of the metabolic effects caused by exposure to the space flight environment. Intake was consistent in quality and quantity throughout the 28, 59 and 84-day flights for each of the crewmen and complete collections were accomplished. The results indicated an increased excretion in most amino acids during the first month of flight which remained elevated in the second and third months but to a lesser extent. Additional indications of change in muscle and skeletal metabolism were observed. These results point to the desirability of obtaining additional indices of alterations in protein synthetic processes in conjunction with future space flights.     

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.     

U.S. manned space flight: the first twenty years, a biomedical status report.

In the last 20 years, the biomedical problems facing man in space have been brought into sharper focus. Space motion sickness is presently our most serious problem. Its etiology remains obscure, but the "sensory conflict" theory appears most plausible. No valid predictive tests of susceptibility exist and presently we must rely on medication for prevention or mitigation of symptoms. Adaptation/biofeedback techniques may prove useful. Cardiovascular "deconditioning" may be effectively attenuated by use of anti-g suits or plasma expanding techniques. Recent bedrest simulation studies would seem to indicate that concerns about chronically elevated central venous pressure during space flight are unfounded. The loss of red cell mass in space flight appears to be self-limited, independent of mission duration, and not of clinical concern, based on recent Soviet experiences. And finally, clodronate, a new diphosphonate effective in preventing hypercalciuria and negative calcium balance in normal human bedrested subjects, may prove effective in preventing or lessening skeletal mineral loss in space.     

Bone loss during long term space flight is prevented by the application of a short term impulsive mechanical stimulus

In long term space flight, the mechanical forces applied to the skeleton are substantially reduced and are altered in character. This reduced skeletal loading results in a reduction in bone mass. Exercise techniques currently used in space can maintain muscle mass but the mechanical stimulus provided by this exercise does not prevent bone loss. By applying an external impulsive load for a short period each day, which is intended to mimic the heel strike transient, to the lower limb of an astronaut during a long term space flight (5 months), this study tests the hypothesis that the bone cells can be activated by an appropriate external mechanical stimulus to maintain bone mass throughout prolonged periods of weightlessness. A mechanical loading device was developed to produce a loading of the os-calcis similar to that observed during the heel strike transient. The device is activated by the astronaut to provide a transient load to the heel of one leg whilst providing an equivalent exercising load to the other leg. During the EUROMIR95 mission on the MIR space station, an astronaut used this device for a short period daily throughout the duration of the mission. Pre- and post-flight measurements of bone mineral density (BMD) of the os-calcis and femoral neck of the astronaut were made to determine the efficacy of the device in preventing loss of bone mineral during the mission. On the os-calcis which received the mechanical stimulus, BMD was maintained throughout the period of the flight, while it was reduced by up to 7% on the os-calcis which received no stimulus. Post-flight, BMD in both the stimulated and non-stimulated os-calcis reduces, the extent of this reduction however is less in the stimulated os-calcis. For the femoral neck, the mechanical stimulation does not produce a positive effect.     

Reloading partly recovers bone mineral density and mechanical properties in hind limb unloaded rats

Skeletal unloading results in decreased bone formation and bone mass. During long-term space flight, the decreased bone mass is impossible to fully recover. Therefore, it is necessary to develop the effective countermeasures to prevent spaceflight-induced bone loss. Hindlimb Unloading (HLU) simulates effects of weightlessness and is utilized extensively to examine the response of musculoskeletal systems to certain aspects of space flight. The purpose of this study is to investigate the effects of a 4-week HLU in rats and subsequent reloading on the bone mineral density (BMD) and mechanical properties of load-bearing bones.     

Prevention of space flight induced soft tissue calcification and disuse osteoporosis.

This paper emphasizes the devastating effects of displacement of calcium during space flight, due to increased bone turnover.     

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.     

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.     

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.     

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.     

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.     

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.