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Urine output in astronauts following ingestion of an oral water load was low in space on the Russian space station Mir and less than during simulation by 6 degrees head-down bed rest. This surprising observation shows that the effects of gravity and weightlessness on fluid volume regulation are not well understood and that the head-down bed-rest model does not simulate the effects of weightlessness on renal water handling.
BACKGROUND: Significant losses in bone density and mineral, primarily in the lower extremities, have been reported following exposure to weightlessness. Recent investigations suggest that mechanical influences such as bone deformation and strain rate may be critically important in stimulating new bone formation. HYPOTHESIS: It was hypothesized that velocity, cadence, and harness design would significantly affect lower limb impact forces during treadmill exercise in simulated zero-gravity (0G). METHODS: A ground-based hypogravity simulator was used to investigate which factors affect limb loading during tethered treadmill exercise. A fractional factorial design was used and 12 subjects were studied. RESULTS: The results showed that running on active and passive treadmills in the simulator with a tethering force close to the maximum comfortable level produced similar magnitudes for the peak ground reaction force. It was also found that these maximum forces were significantly lower than those obtained during overground trials, even when the speeds of locomotion in the simulator were 66% greater than those in 1G. Cadence had no effect on any of the response variables. The maximum rate of force application (DFDTmax) was similar for overground running and exercise in simulated 0G, provided the "weightless" subjects ran on a motorized treadmill. CONCLUSIONS: These findings have implications for the use of treadmill exercise as a countermeasure for hypokinetic osteoporosis. As the relationship between mechanical factors and osteogenesis becomes better understood, results from human experiments in 0G simulators will help to design in-flight exercise programs that are more closely targeted to generate appropriate mechanical stimuli.
The explanation of the mechanism of the response to gravity changes is of great importance for the determination of the capacity of human subjects to adapt to the load of gravitational stress. Therefore several studies were performed to investigate the activity of endocrine system, since the hormones are involved in the regulation of physiological functions and metabolic processes. However the studies of endocrine system activity during altered gravity conditions, especially during the weightlessness are influenced by the several interventions in biomedical observations due to operational program of astronauts, wide variability in individual response and tolerance, use of extensive countermeasures, differences in the type of space missions and in the studies after landing also a hypergravity effect at landing and variability in postflight readaptation process. The significant changes of plasma insulin and glucose levels were observed in astronauts during space flights and in the first days of recovery period. In the first inflight period plasma insulin levels were increased, unchanged or decreased however after 4-5 weeks of exposure to weightlessness a decrease of insulin plasma levels were noted. After space flights an increase of plasma insulin levels were demonstrated in experimental animals and in human subjects. Since plasma insulin level is considered as most important factor involved in the regulation for insulin receptors in target tissues, an investigation of insulin receptors in various tissues was performed in rats exposed to space flight or to hypokinesia (model used for simulation of some effects of microgravity).
Experiments in space have shown that T lymphocyte function is altered in more than 50% of space crew members. There is strong evidence that such effect is due to stress rather than to weightlessness per se. However the health of astronauts was never threatened so far. Experiments in-vitro with cultures of human peripheral blood lymphocytes (not from astronauts) have shown that T cell function is dramatically reduced. Recent work with the random positioning machine, a new instrument to simulate conditions similar to microgravity, indicate that there are direct gravitational effects on the genetic expression of interleukin-2 and of its receptor in T lymphocytes.
BACKGROUND: Performing a surgical procedure in weightlessness, also called 0-gravity (0-g), has been shown to be no more difficult than in a 1-g environment if the requirements for the restraint of the patient, operator, surgical hardware, are observed. The performance of laparoscopic and thorascopic procedures in weightlessness, if feasible, would offer several advantages over the performance of an open operation. Concerns about the feasibility of performing minimally invasive procedures in weightlessness have included impaired visualization from the absence of gravitational retraction of the bowel (laparoscopy) or thoracic organs (thoracoscopy) as well as obstruction and interference from floating debris such as blood, pus, and irrigation fluid. The purpose of this study was to determine the feasibility of performing laparoscopic and thorascopic procedures and the degree of impaired surgical endoscopic visualization in weightlessness. METHODS: From 1993 to 2000, laparoscopic and thorascopic procedures were performed on 10 anesthetized adult pigs weighing approximately 50 kg in the National Aeronautics and Space Administration (NASA) Microgravity Program using a modified KC-135 airplane. The parabolic simulation system for advanced life support was used in this project, and 20 to 40 parabolas were used for laparoscopic or thorascopic investigation, each containing approximately 30 s of 0-g alternating with 2-g pullouts. The animal model was restrained in the supine position on a floor-level Crew Medical Restraint System, and the abdominal cavity was insufflated with carbon dioxide. The intraabdominal and intrathoracic anatomy was visualized in the 1-g, 0-g, and 2-g periods of parabolic flight. Bleeding was created in the animals, and the behavior of the blood in the abdominal and thoracic cavities was observed. In the thoracic cavity, gas insufflation and mechanical retraction was used at times unilaterally to decrease pulmonary ventilation enough to increase the thoracic domain. RESULTS: Visualization was improved in laparoscopy, from tethering of the bowel by the elastic mesentery, and from the strong tendency for debris and blood to adhere to the abdominal wall because of surface tension forces. The lack of adequate thoracic domain made thorascopy more difficult. Fluid in the thoracic cavity did not impair visualization because the fluid at 0-g does not loculate posteriorly, but disperses along the thoracic wall and mediastinal reflections. CONCLUSIONS: Performing minimally invasive procedures instead of open surgical procedures in a weightless environment has theoretical advantages, especially in the ability to prevent cabin atmosphere contamination from surgical fluids (blood, pus, irrigation). Visualization will become more important and practical as the endoscopic hardware is miniaturized from its current form, as endoscopic technology becomes more advanced, and as more surgically capable medical crew officers are present in future long-duration space exploration missions.
Space flight has been shown to affect various bacterial growth parameters. It is proposed that weightlessness allows the cells to remain evenly distributed, consequently altering the chemical makeup of their surrounding fluid, and hence indirectly affecting their physiological behaviour. In support of this argument, ground-based studies using clinostats to partially simulate the quiescent environment attained in microgravity have generally been successful in producing bacterial growth characteristics that mimic responses reported under actual space conditions. A novel approach for evaluating the effects of reduced cell sedimentation is presented here through use of Escherichia coli cultures genetically modified to be neutrally buoyant. Since clinorotation would not (or would only minimally) affect cell distribution of this already near-colloidal cell system, it was hypothesized that the effects on final population density would be eliminated relative to a static control. Gas-vesicle-producing E. coli cultures were grown under clinostat and static conditions and the culture densities at 60 h were compared. As a control, E. coli that do not produce gas vesicles, but were otherwise identical to the experimental strain, were also grown under clinostat and static conditions. As hypothesized, no significant difference was observed in cell populations at 60 h between the clinorotated and static gas-vesicle-producing E. coli cultures, while the cells that did not produce gas vesicles showed a mean increase in population density of 10.5 % (P = 0.001). These results further suggest that the lack of cumulative cell sedimentation is the dominant effect of space flight on non-stirred, in vitro E. coli cultures.
The effect of flight factors on the growth and development of the fruit bodies of the higher fungus Polyporus brumalis is investigated under the conditions of an experiment on the earth satellite Cosmos 690. Fungi were grown on the earth under conditions of simulated flight and transit; fungi were also grown in the laboratory at a temperature similar to that in flight, at various orientations and under various illuminations. Polyporus brumalis grows well on wort; it forms fruit bodies on long pedicles (up to 25 cm) and possesses a strongly marked negative geotropism. Investigations have shown that the formation of hymenium and pileus is induced by definite time exposures to light. In darkness the formation of fruit bodies takes place, but without formation of hymenium and pileus, and the rate of growth is greater than in light. The strong negative geotropism remains in fruit bodies when developed in darkness and with test-tubes in a vertical position. When the test-tube orientation is changed the pedicles change direction in darkness as well as in light. In maintaining their negative geotropism the fruit bodies bend with changes of space orientation. In the absence of gravity a disorientation of fruit bodies takes place, and the pedicles are strongly twisted into a spiral or into a ball. A flattened type of fruit body can also occur. Such a picture of growth and formation was not observed in control samples. Thus, there is a strong dependence of the formation of the fruit body of Polyporus brumalis on space orientation, gravity and light.
BACKGROUND: Medical operations on the International Space Station will emphasize the stabilization and transport of critically injured personnel and so will need to be capable of advanced trauma life support (ATLS). METHODS: We evaluated the ATLS invasive procedures in the microgravity environment of parabolic flight using a porcine animal model. Included in the procedures evaluated were artificial ventilation, intravenous infusion, laceration closure, tracheostomy, Foley catheter drainage, chest tube insertion, peritoneal lavage, and the use of telemedicine methods for procedural direction. RESULTS: Artificial ventilation was performed and appeared to be unaltered from the 1-G environment. Intravenous infusion, laceration closure, percutaneous dilational tracheostomy, and Foley catheter drainage were achieved without difficulty. Chest tube insertion and drainage were performed with no more difficulty than in the 1-G environment due to the ability to restrain patient, operator and supplies. A Heimlich valve and Sorenson drainage system were both used to provide for chest tube drainage collection with minimal equipment, without the risk of atmospheric contamination, and with the capability to auto-transfuse blood drained from a hemothorax. The use of telemedicine in chest tube insertion was demonstrated to be useful and feasible. Peritoneal lavage using a percutaneous technique, although requiring less training to perform, was found to be dangerous in weightlessness due to the additional pressure of the bowel on the anterior abdominal wall creating a high risk of bowel perforation. CONCLUSIONS: The performance of ATLS procedures in microgravity appears to be feasible with the exception of diagnostic peritoneal lavage. Minor modifications to equipment and techniques are required in microgravity to effect surgical drainage in the presence of altered fluid dynamics, to prevent atmospheric contamination, and to provide for the restraint requirements. A parabolic simulation system was developed for equipment and procedure verification, physiological research, and possible crew medical officer training in the future.
Disuse can induce numerous adaptive alterations in skeletal muscle. In the present study the effects of hindlimb unloading on muscle mass and biochemical responses were examined and compared in adult (450 g) and juvenile (200 g) rats after 1, 7, or 14 days of whole body suspension. Quantitatively and qualitatively the soleus (S), gastrocnemius (G), plantaris (P), and extensor digitorum longus (EDL) muscles of the hindlimb exhibited a differential sensitivity to suspension and weightlessness unloading in both adults and juveniles. The red slow-twitch soleus exhibited the most pronounced atrophy under both conditions, with juvenile responses being greater than adult. In contrast, the fast-twitch EDL hypertrophied during suspension and atrophied during weightlessness, with no significant difference between adults and juveniles. Determination of biochemical parameters (total protein, RNA, and DNA) indicated a less rapid rate of response in adult muscles. This was corroborated by assessment of muscle alpha-actin mRNA levels, which indicated a rapid (within 1 day) and significant (P less than 0.05) effect in juveniles but not in adults. The results of this investigation indicate 1) a qualitatively similar differential effect of unloading on muscles of adults and juveniles, 2) a quantitatively reduced and less rapid effect of suspension on adult muscles, and 3) a close similarity of adult and juvenile muscle responses during suspension and spaceflight, suggesting that this ground-based model simulates many of the unloading effects of weightlessness.
The need to acquire a better knowledge of the main biological problems induced by microgravity implies--in addition to human experimentation--the use of animal models, and primates seem to be particularly well adapted to this type of research. The major areas of investigation to be considered are the phospho-calcium metabolism and the metabolism of supporting tissues, the hydroelectrolytic metabolism, the cardiovascular function, awakeness, sleep-awakeness cycles, the physiology of equilibrium and the pathophysiology of space sickness. Considering this program, the Centre d'Etudes et de Recherches de Medecine Aerospatiale, under the sponsorship of the Centre National d'Etudes Spatiales, developed both a program of research on restrained primates for the French-U.S. space cooperation (Spacelab program) and for the French-Soviet space cooperation (Bio-cosmos program), and simulation of the effects of microgravity by head-down bedrest. Its major characteristics are discussed in the study.
Many human responses to the weightless environment have been documented from actual spaceflights. These include physiological effects on the nervous system, cardiovascular system and fluid balance, and the musculoskeletal system, as well as psychological effects. Simulations on Earth have added to our knowledge about the physiology of weightlessness. Early data on orthostatic intolerance after real and simulated spaceflight led some scientists to discourage a high level of aerobic fitness for astronauts. They believed it was detrimental to orthostatic tolerance on return to Earth. However, most of the data available today do not support this contention. Furthermore, aerobic fitness is beneficial to cardiovascular function and mental performance. Therefore, it may be important in performing extra-vehicular activities during flight. Some astronauts claim exercise enhances their feeling of well-being and self image. And, although the cardiovascular system and exercise performance may recover more slowly after flight to preflight levels when fitness level prior to flight is high, the musculoskeletal system may recover more rapidly. Research is needed to determine optimal levels of aerobic training for performing tasks in flight, maintaining health and well-being during flight, and assuring satisfactory recovery on return to Earth.
Plasma and tissue lipids in male SPF Wistar rats flown for 18.5 days aboard the Cosmos 936 biosatellite were analyzed. One group of rats was subjected to artificial gravity by use of a centrifuge during the flight. An experiment simulating known space flight factors other than weightlessness was done on Earth. An increase of total cholesterol in plasma, of nonesterified fatty acids in plasma and brown adipose tissue, of triacylglycerols in plasma, liver, thymus and bone marrow was noted several hours after biosatellite landing. Smaller changes were observed in the terrestrial control experiment. With the exception of triacylglycerol accumulation in bone marrow, these increases disappeared 25 days after biosatellite landing. Exposing the rats aboard the biosatellite to artificial gravity was beneficial in the sense that such exposure inhibited the phospholipid and triacylglycerol increase in plasma and inhibited the increase of triacylglycerol in liver and especially in bone marrow.
Wheat seedlings in weightlessness aboard NASA Biosatellite 2 differ from ground control seedlings in mitotic count, cell length and nuclear volume as well as in orientation, starch grain distribution, organ length and malformations previously reported to COSPAR. Dividing cells are fewer in roots of orbited seedlings than in erect or clinostat ground controls. The greatest difference is among cells in early prophase. Root cells, proximal to the zone of cell division are longer in flight seedlings than erect or clinostat ground controls. As the roots are the same length, greater elongation compensates for the reduced rate of cell division. Volume of interphase nuclei in all seedling organs is increased by orbital flight. In clinostat controls, only nuclei of primary roots increase in size. Between 58 and 65 hours of age, nuclear volume in erect 1 g coleoptiles decreases; in flight seedlings it increases. Simulated launch vibration, alone or followed by growth on the clinostat, increases nuclear volume in some roots, but coleoptile nuclei do not respond as in flight seedlings. Thus, at the cellular level, orbital flight cannot be exactly duplicated by the clinostat whether preceded by vibration or not.
Mammalian reproduction evolved within Earth's 1-g gravitational field. As we move closer to the reality of space habitation, there is growing scientific interest in how different gravitational states influence reproduction in mammals. Habitation of space and extended spaceflight missions require prolonged exposure to decreased gravity (hypogravity, i.e., weightlessness). Lift-off and re-entry of the spacecraft are associated with exposure to increased gravity (hypergravity). Existing data suggest that spaceflight is associated with a constellation of changes in reproductive physiology and function. However, limited spaceflight opportunities and confounding effects of various nongravitational factors associated with spaceflight (i.e., radiation, stress) have led to the development of ground-based models for studying the effects of altered gravity on biological systems. Human bed rest and rodent hindlimb unloading paradigms are used to study exposure to hypogravity. Centrifugation is used to study hypergravity. Here, we review the results of spaceflight and ground-based models of altered gravity on reproductive physiology. Studies utilizing ground-based models that simulate hyper- and hypogravity have produced reproductive results similar to those obtained from spaceflight and are contributing new information on biological responses across the gravity continuum, thereby confirming the appropriateness of these models for studying reproductive responses to altered gravity and the underlying mechanisms of these responses. Together, these unique tools are yielding new insights into the gravitational biology of reproduction in mammals.
Weightlessness influences the human immune and hormone system, reduces bone mass, leads to muscle atrophy and cardiac atrophy. Effects on control mechanisms for proliferation, programmed cell death and differentiation are well documented. The principal aim of this study was to investigate changes of the cytoskeleton in thyroid cells cultured in vector-averaged gravity under clinostat rotation. After 12 hours the formation of multicellular spheroids started. An increase of extracellular matrix proteins and beta 1-integrin was observed. Laser scanning confocal microscopy of ML-1 follicular thyroid carcinoma cells and normal thyroid HTU-5 cells immunostained with anti-cytokeratin to demonstrate these intermediate filaments revealed that cytokeratin filaments extended from centers, were thickened, coalesced and shortened as compared to control cells. Moreover, vimentin was highly disorganized. The vimentin network formed a coiled aggregate closely associated with the nucleus. Western blot analyses of talin, alpha- and beta-tubulin showed a clear increase of these proteins in cells cultured under simulated 0 g. Our data suggest that the effects of microgravity on cultured human thyroid cells are accompanied by noticeable functional cellular changes. Future studies to clarify the pathway that regulate the observed integrin activation and the mechanisms by which they function have to be performed.
The venturing forth of man into space confronts the surgeon with a new weightless environment with which he will inevitably have to contend. In this study operative procedures were performed on 20 rats in a simulated space environment with use of neutral buoyancy in order to identify those factors that could actually or potentially affect operative technique. There are three general areas of difference from normal conditions in simulated microgravity: physical adaptation to gravity deprivation tissue behavior, including bleeding; and the conduct of surgery. Without gravity, the tactile "feel" of objects is changed ("heavy" and "light" are meaningless terms) and proprioception is confused so that there is past pointing and overreaching of movements. Tissue planes tend to separate, and organs float and bob in the operative field, which makes clamping, cutting, and suturing different. Bleeding is a major consideration; surface tension tends to keep venous blood oozing along surfaces, whereas pulsatile arterial blood forms droplets, streamers, and clouds, depending on the force of the bleeding. These factors and others interfere with surgical technique in a number of ways: dispersion of blood obscures the surgeon's vision, sutures become entangled, organs are not stabilized, and instruments float into the operative field. The limitations of comparing neutral buoyancy to the true zero gravity of space are addressed. There is a definite need for further investigation for development of new surgical techniques in preparation for experimental and clinical surgery in space.
Different mathematical models of varying complexity have been proposed in recent years to study the cardiovascular (CV) system. However, only a few of them specifically address the response to lower body negative pressure (LBNP), a stress that can be applied in weightlessness to predict changes in orthostatic tolerance. Also, the simulated results produced by these models agree only partially with experimental observations. In contrast, the model proposed by Melchior et al., and modified by Karam et al. is a simple representation of the CV system capable of accurately reproducing observed LBNP responses up to presyncopal levels. There are significant changes in LBNP response due to a loss of blood volume and other alterations that occur in weightlessness and related one-g conditions such as bedrest. A few days of bedrest can cause up to 15% blood volume loss (BVL), with consequent decreases in both stroke volume and cardiac output, and increases in heart rate, mean arterial pressure, and total peripheral resistance. These changes are more pronounced at higher levels of LBNP. This paper presents the results of a simulation study using our CV model to examine the effect of BVL on LBNP response.
The human cardiovascular system and regulation of fluid volume are heavily influenced by gravity. When decreasing the effects of gravity in humans such as by anti-orthostatic posture changes or immersion into water, venous return is increased by some 25%. This leads to central blood volume expansion, which is accompanied by an increase in renal excretion rates of water and sodium. The mechanisms for the changes in renal excretory rates include a complex interaction of cardiovascular reflexes, neuroendocrine variables, and physical factors. Weightlessness is unique to obtain more information on this complex interaction, because it is the only way to completely abolish the effects of gravity over longer periods. Results from space have been unexpected, because astronauts exhibit a fluid and sodium retaining state with activation of the sympathetic nervous system, which subjects during simulations by head-down bed rest do not. Therefore, the concept as to how weightlessness affects the cardiovascular system and modulates regulation of body fluids should be revised and new simulation models developed. Knowledge as to how gravity and weightlessness modulate integrated fluid volume control is of importance for understanding pathophysiology of heart failure, where gravity plays a strong role in fluid and sodium retention.