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.     

Excretion of amino acids by humans during space flight

We measured the urine amino acid distribution patterns before, during and after space flight on the Space Shuttle. The urine samples were collected on two separate flights of the space shuttle. The first flight lasted 9.5 days and the second flight 15 days. Urine was collected continuously on 8 subjects for the period beginning 10 d before launch to 6 d after landing. Results: In contrast to the earlier Skylab missions where a pronounced amino aciduria was found, on shuttle the urinary amino acids showed little change with spaceflight except for a marked decrease in all of the amino acids on FD (flight day) 1 (p<0.05) and a reduction in isoleucine and valine on FD3 and FD4 (p<0.05). Conclusions: (i) Amino aciduria is not an inevitable consequence of space flight. (ii) The occurrence of amino aciduria, like muscle protein breakdown is a mission specific effect rather than part of the general human response to microgravity.     

Endocrine responses in long-duration manned space flight

The bioassay of body fluids experiment is designed to evaluate the biochemical adaptation resulting from extended exposure to space flight environment by identifying changes in hormonal and associated fluid and electrolyte parameters reflected in the blood and urine of the participating crewmen. The combined stresses of space flight include weightlessness, acceleration, confinement, restraint, long-term maintenance of high levels of performance, and possible desynchronosis. Endocrine measurements to assess the physiological cost of these stresses have been considered from two aspects. Fluid and electrolyte balance have been correlated with weight loss, changes in the excretion of aldosterone and vasopressin and fluid compartments. The second area involves the estimation of the physiological cost of maintaining a given level of performance during space flight by analysis of urinary catecholamines and cortisol. Inter-individual variability was demonstrated in most experimental indices measured; however, constant patterns have emerged which include: body weight change; increases in plasma renin activity; elevations in urinary catecholamines, ADH, aldosterone and cortisol concentrations. Plasma cortisol decreases in immediate postflight samples with subsequent increase in 24-hour urines. The measured changes are consistent with the prediction that a relative increase in thoracic blood volume upon transition to the zero-gravity environment is interpreted as a true volume expansion resulting in an osmotic diuresis. This diuresis in association with other factors ultimately results in a reduction in intravascular volume, leading to an increase in renin and a secondary aldosteronism. Once these compensatory mechanisms are effective in reestablishing positive water balance, the crewmen are considered to be essentially adapted to the null-gravity environment. Although the physiological cost of this adaptation must reflect the electrolyte deficit and perhaps other factors, it is assumed that the compensated state is adequate for the demands of the environment; however, this new homeostatic set is not believed to be without physiological cost and could, except with proper precautions, reduce the functional reserve of exposed individuals.     

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.     

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.     

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.     

Space motion sickness medications: interference with biomedical parameters

The possibility that drugs administered to Skylab 3 (SL-3) and 4 (SL-4) crewmen for space motion sickness may have interfered with their biomedical evaluation in space was investigated. Healthy volunteers received combinations of Scopolamine/Dexedrine for four days in regimens similar to those used in these missions. Urine samples, heart rate, body temperature, mood and performance were analyzed for drug-related changes. Twenty-four hour urine samples were analyzed by the same procedures as those used to analyze the flight samples. Hormone concentrations determined included cortisol, epinephrine, norepinephrine, aldosterone and antidiuretic hormone (ADH). In addition, volume, specific gravity, osmolarity, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), inorganic phosphate, uric acid and creatinine were measured. Performance was not affected by the Scopolamine/Dexedrine. The drug combination increased daily mean heart rate (HR) significantly in all the subjects and daily mean rectal temperature (RT) in some of the subjects. A 2-4 hr phase shift in the HR circadian rhythm was also observed which indicates that internal circadian synchrony was disturbed by the drugs. Psychological and subjective evaluation indicated that the subjects could usually identify which days they were given the drugs by an increase in tension and anxiety, decreased patience, restlessness, decreased appetite, difficulty in sleeping and feelings of increased heart rate and body temperature. Urinary electrolytes were not changed significantly by the drug, but marked and significant changes occurred in urine volume and hormone excretion patterns. Scopolamine/Dexedrine caused consistent elevations in urinary cortisol and epinephrine and a transient elevation in ADH. Norepinephrine excretion was decreased, but there was no significant change in aldosterone excretion or in 24 hr urine volume. A comparison of these findings with the first four days of inflight data from the SL-3 and SL-4 missions leads to the conclusion that the dramatic increases in aldosterone excretion during the first three days of spaceflight probably can be directly attributed to weightlessness, whereas the antimotion sickness medication could have substantially contributed to the early increased excretion of epinephrine and cortisol during these missions.     

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.     

Changes in chromatin and nucleic acids in rat tissues after two-week spaceflight

The quantitative changes in nucleic acids and chromatin breakdown were followed in blood, thymus and spleen in rats after 14 day flights on board the biosatellites Cosmos-1887 and Cosmos-2044. Quantitative nucleic acid changes within 8-11 h after landing were only mild, most statistically non-significant. An analysis at 48 h after landing showed a marked decrease in a total content of DNA and RNA in spleen and thymus. Within 8-11 h after landing, the symptoms of chromatin breakdown were found as is seen in an increased concentration of its fragments-polydeoxyribonucleotides. The obtained results show that a partial adaptation to microgravity occurs up to flight day 14 in lymphoid organs. Adaptation is accompanied with a reappearing of the sensitive cells. Their chromatin breaks down, then, in a final phase of flight due to hypergravity stress manifesting itself by a temporary increase in polydeoxyribonucleotide concentration several hours after landing. The results are discussed in relation to the changes in chosen parameters after shorter or more prolonged flights.     

基于气动辅助变轨的变气动外形飞行器概念研究--最优控制律问题

从一个天地往返飞行器的上升轨道和再入返回轨道的优化，以及适用不同飞行任务的变轨要求的气动外形问题，提出一项基于气动力辅助变轨的变气动外形飞行器的新概念研究。对于一个固定气动外形飞行器要同时满足上升轨道有效载荷最大和再入轨道热流峰值、过载峰值及机动性能约束下的成本最低往往是困难的。若同时满足不同飞行任务：飞往太空站的运输任务，空间拦截和交会机动巡航任务及星际探测任务，则更为困难，实际上是不可能的。文章研究基于气动力辅助变轨，在热流约束下，气动外形参数变化对最优控制的影响。其结论为：热流约束下的最优控制解，包括考虑推力协同变轨，除了在非约束弧的滚转角不直接受气动外形影响外，其余的控制律，升力系数和滚转角都是气动外形参数和攻角的函数。因而变气动外形可作为一项新技术，即通过气动外形参数变化和相应的变轨策略而获得性能和成本都最佳的用途很广的一种新型飞行器。     

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.     

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.     

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.     

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.     

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.     

Natural killer cells after ALTAIR mission

Reduced in vitro NK cytotoxic activity have routinely been observed after both prolonged and short-term space flights. This study investigated the effects of space flight on NK cell functions, NK cell counts and the production of IL-2 and TNF by lymphocytes of French-Russian crew members. In the French cosmonaut, after 21 days space flight, the cytotoxic activity of NK cells, the capacity the NK cells to bind and lyse the individual target cells and the percentage of NK cells were decreased. In this cosmonaut a twofold reduction TNF production in cultures of lymphocytes stimulated with PMA and with the mixture of PHA and PMA was observed on the first day after landing. However, the activity of the production of TNF in 48-hour PHA-cultures of lymphocytes was unchanged and the biological activity of IL-2 was not reduced. The immunological examination did not detecte any substantial deviations from the norm in both russian cosmonauts after 197 days space flight. Various explanations for decreased cytotoxicity in cosmonauts after space flight can be proposed, and these include the defective function of NK cells and reduced numbers of circulating effector cells.     

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.     

Skylab experiment M-171 "Metabolic Activity"--results of the first manned mission

The experiment was performed to ascertain whether man's ability to perform mechanical work would be altered as a result of exposure to the weightless environment. Skylab II crewmen were exercised on a bicycle ergometer at loads approximating 25%, 50%, and 75% of their maximum oxygen uptake while their physiological responses were monitored. The results of these tests indicate that the crewmen had no significant decrement in their response to exercise during their exposure to zero gravity. Immediately postflight, however, all crewmen demonstrated an inability to perform the programmed exercise with the same metabolic effectiveness as they did both preflight and inflight. The most significant changes were elevated heart rates for the same work load and oxygen consumption (decreased oxygen pulse), decreased stroke volume, and decreased cardiac output at the same oxygen consumption level. It is apparent that the changes occurred inflight, but did not manifest themselves until the crewmen attempted to readapt to the 1-G environment.     

Short duration microgravity experiments in physical and life sciences during parabolic flights: the first 30 ESA campaigns

Aircraft parabolic flights provide repetitively up to 20 s of reduced gravity during ballistic flight manoeuvres. Parabolic flights are used to conduct short microgravity investigations in Physical and Life Sciences, to test instrumentation and to train astronauts before a space flight. The European Space Agency (ESA) has organized since 1984 thirty parabolic flight campaigns for microgravity research experiments utilizing six different airplanes. More than 360 experiments were successfully conducted during more than 2800 parabolas, representing a cumulated weightlessness time of 15 h 30 m. This paper presents the short duration microgravity research programme of ESA. The experiments conducted during these campaigns are summarized, and the different airplanes used by ESA are shortly presented. The technical capabilities of the Airbus A300 'Zero-G' are addressed. Some Physical Science, Technology and Life Science experiments performed during the last ESA campaigns with the Airbus A300 are presented to show the interest of this unique microgravity research tool to complement, support and prepare orbital microgravity investigations.