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Orientation illusions in spaceflight.

Investigations of spontaneous illusory reactions were carried out during space-flights of various durations by ANKETA questionnaires (104 cosmonauts). From a total of 104 cosmonauts, 24, in addition, used a dictaphone to record a verbal description of the illusions and their sensations on tape. Analysis of data generated by ANKETA and the tapes thus recorded have shown that during adaptation to weightlessness, 98% of cosmonauts have noted the occurrence of various illusions of orientation (coordinate and kinetic): illusions pertaining to their position or illusions of self- and surround-motion. The development of spatial orientation illusions during and after flight is not limited to certain individuals, but is a general response of the sensory system to microgravity. These responses differ to some extent among individuals in severity, nature, time and duration of occurrence, and the dynamics of the process. Perceptual disorders may occur even if the cosmonaut feels well and experiences no anomalous autonomic reactions. The nature of spatial illusions was determined by the role and relative contribution of various types of sensory input to spatial orientation. After completion of the initial stage of adaptation to weightlessness, the perceptual disorders disappear. However, spontaneous illusory reactions were often observed after 50 days of exposure to weightlessness. The adaptation process during long-term spaceflight had an undulating course, in which adaptation and de-adaptation alternated. A classification of weightlessness illusions is proposed.

Adaptation, Physiological↗

Mathematical modeling of acute and chronic cardiovascular changes during Extended Duration Orbiter (EDO) flights.

The Extended Duration Orbiter (EDO) program aims to extend the capability of the Shuttle orbiter beyond its current 7-10 day limit on mission duration. This goal is to be accomplished in steps, partly due to our limited knowledge of the physiological changes resulting from long-term exposure to weightlessness and their likely influence on critical mission operations involved in EDO flights. Answers to questions related to physiologic adaptation to weightlessness are being actively sought at the present time to help implement the EDO program. In the cardiovascular area, the loss of orthostatic tolerance is a medical concern because of its potential adverse effects on crew performance and safety during reentry and following return to earth. Flight and ground-based physiologic studies are being planned to understand the mechanism and time course of spaceflight-induced orthostatic intolerance and to develop effective countermeasures for improving post-flight cardiovascular performance. Where feasible, these studies are aided by theoretical analyses using mathematical modeling and computer simulation of physiological systems. This paper is concerned with the application of proven models of circulatory and cardiovascular systems in the analysis of chronic cardiovascular changes under weightless conditions.

Cardiovascular Deconditioning↗

Analysis of heart rate variability and its application.

Heart rate variability (HRV) has considerable potentials in assessing the role of autonomic nervous system fluctuations in healthy individuals and patients. This paper reviews the analytical methods of HRV and its application. HRV is a useful parameter for predicting cardiac risk after acute myocardial infarction, and an early warning sign of diabetes neuropath in clinical medicine. In space medical studies, HRV analysis have been used to assess changes in autonomic regulation after weightlessness or simulated weightlessness, evaluate tolerance in various stress test, study regulatory mechanisms of cardiovascular system, and assess the effect of countermeasure against weightlessness.

Aerospace Medicine↗

Pharmacology in space: pharmacotherapy.

This chapter summarized the information available on the pharmacological kits onboard spacecraft and on the use of drugs in space, while the next chapter is dedicated to the impacts of weightlessness on drug pharmacokinetics. The need of a selected group of drugs for the use of astronauts during short-term and long-term spaceflights has been discussed. Recommendations are made for a Space Pharmacopoeia as well as for the areas of research needed to adapt medication to the weightlessness of the space environment. Although the usefulness of these drugs has been clearly demonstrated, their use also raises several problems. Physiological changes due to weightlessness may induce changes in pharmacokinetic behavior of drugs and influence their dosage regimen. Inflight data obtained by salivary drug monitoring have shown changes in the distribution of scopolamine and a significant change in the disposition of the common pain-relief agent acetaminophen taken inflight, in both drug concentration and time course. The authors of this study emphasize, however, that their data are preliminary and as yet incomplete. Further simulation studies and, if possible, inflight experiments are required. In vitro studies of the antibacterial activity of antibiotics under space conditions have shown an increased resistance of Escherichia Coli to colistin and kanamycin, and a lowered resistance of Staphylococcus Aureus to oxacillin, chloramphenicol, and erythromycin. The possible consequences of these findings for the treatment of infections contracted by astronauts are yet to be elucidated. There is still a lack of pharmacological countermeasures, particularly for preventing the progressive bone demineralization occurring in weightlessness. The treatment of space motion sickness with drugs carries with it the problem of undesirable side-effects on psychomotor performance. In order to arrive at the most appropriate medical kit for a particular mission, the best trade-off of risk versus benefit for the individual and the mission must always be attempted for any pharmacological agent.

Aerospace Medicine↗

A novel pharmacological approach of musculoskeletal losses associated with simulated microgravity.

Exposure to microgravity (weightlessness) is known to cause rapid bone and muscle losses. We have used the hind limb-suspended (HLS) rat model to simulate microgravity-induced musculoskeletal losses in order to assess resulting hormonal changes and to develop a novel pharmacological countermeasure. Previously, we demonstrated significant decreases in circulatory hormonal levels [serum thyroxin, 1,25(OH)2 vitamin D (p<0.05), and serum testosterone (p<0.001)] in HLS rats. Both thyroxin and 1,25(OH)2 vitamin D levels returned to normal soon after removal from HLS, while testosterone levels matched normal levels only after a further 3-4 weeks. However, even by day 42, bone mineral density (BMD) remained significantly lower, although serum hormones were back to normal. Because serum testosterone levels become undetectable in HLS rats, we hypothesized that the replacement of testosterone during HLS could prevent musculoskeletal losses. Based on these data, an intervention study was carried out to assess the efficacy of testosterone and synthetic anabolic steroid, nandrolone decanoate (ND), in prevention of weightlessness-induced musculoskeletal losses. HLS rats (control) had a significant reduction of muscle volume (42.9 -/+ 3.0, versus 56 -/+ 1.8 in ground control rats; p<0.01). Both testosterone and ND treatments prevented this muscle loss (51.5 -/+ 2 cm(3) and 51.6 -/+ 1.2, respectively; a 63% improvement, p<0.05). Similarly, BMD of the placebo-treated HLS rats was significantly lower than that of ground control rats (0.416 -/+ 0.011 versus 0.354 -/+0.014, p<0.05), and testosterone and ND prevented this bone loss (0.404 -/+ 0.013 versus. 0.409 -/+ 0.011, respectively). These data suggest that both testosterone and ND therapy can minimize the musculoskeletal losses associated with exposure to simulated weightlessness. Experiments using the combination of bisphosphonate and testosterone demonstrated complete protection of both muscle and bone in these HLS rats. Therefore, considering that: 1) testosterone is anabolic to osteoblasts and muscle cells and also decreases the rate of bone turnover, 2) serum testosterone levels are markedly suppressed in simulated weightlessness, and 3) testosterone replacement therapy prevented musculoskeletal losses in HLS rats, we propose that the musculoskeletal losses observed in this animal model (i.e., simulated microgravity) are related to their testosterone deficiency. Since serum sex hormones levels are markedly reduced in this model of simulated microgravity, androgen replacement with a bisphosphonate seems to be a rational counter.

Journal Article↗

[Effect of artificial gravity during space flight on protein and RNA concentration in motoneurons of the anterior horns of the spinal cord in rats].

The content of protein and RNA in motoneurons of anterior horns of the spinal cord of rats flown for 18.5 days aboard the biosatellite Cosmos--936 was measured. Ten rats were exposed to weightlessness and 9 rats to artificial gravity. The RNA content in both rat groups remained at the preflight level 4.5--9.5 hours after recovery. The protein content in the motoneuronal cytoplasm of weightless and centrifuged rats was by 42 and 30% lower than in vivarium control. The protein content in the motoneuronal nuclei of the above rats was by 31 and 24% lower than in the controls. Twenty-five days postflight the RNA content in weightless rats was by 22% higher than and in centrifuged rats similar to that in the controls. The protein content in the cytoplasm returned to normal in both rat groups, whereas that in the nuclei of weightless rats was by 37% higher than in the controls.

Animals↗

Effects of altered gravity on the actin and microtubule cytoskeleton of human SH-SY5Y neuroblastoma cells.

Human SH-SY5Y neuroblastoma cells were used to study the effects of altered gravity on the actin and microtubule cytoskeleton dynamics. A cholinergic stimulation of the cells during a 6 min period of changing gravity (3 parabolas) resulted in an enhanced actin-driven protrusion of evoked lamellipodia. Likewise, the spontaneous protrusive activity of nonactivated cells was promoted during exposure to changing gravity (6 up to 31 parabolas). Ground-based experiments revealed a similar enhancement of the spontaneous and evoked lamellar protrusive activity when the cells were kept at 2 g hypergravity for at least 6 min. This gravity response was independent of the direction of the acceleration vector in respect to the cells. Exposure of the cells to "simulated weightlessness" (clinorotation) had no obvious influence on this type of lamellar actin cytoskeleton dynamics. A 20 min exposure of the cells to simulated weightlessness or to changing gravity (6 to 31 parabolas) - but not to 2 g (hypergravity, centrifugation) - resulted in an altered arrangement of microtubules indicated by bending, turning, and loop formation. A similar altered arrangement was shown by microtubules which had polymerized into lamellipodia after release from a taxol block at simulated weightlessness (clinorotation) or during changing gravity (5 parabolas). Our data suggest that in human SH-SY5Y neuroblastoma cells, microgravity affects the dynamics and spatial arrangement of microtubules but has no influence on the Rac-controlled lamellar actin cytoskeleton dynamics and cell spreading. The latter, however, seems to be promoted at hypergravity.

Acetylcholine↗

Bone mineral measurement: Skylab experiment M-078.

The observation that bone mineral is lost in patients who are either immobilized or remain in bed for extended periods of time formed the basis for the concern that large amounts of bone mineral may be lost during long periods of weightlessness. This concern was magnified when early X-ray densitometry studies suggested that rather large amounts of mineral could be lost during rather short periods of weightlessness (4-14 days). Even though these Gemini results have recently been modified, they still reflect substantial losses in the upper extremity. This led to a series of prolonged bed-rest studies (30-36 weeks) which, in addition to careful calcium balance, also employed a newer, more precise method of estimating bone mineral in the radius, ulna, and os calcis. It employed an essentially monoenergetic photon source (125I) and a scintillation detector operating in a rectilinear scanning mode to measure bone mineral by the absorptiometric technique. Bed-rest studies revealed variable mineral losses but suggested that little if any is lost during 4-6 weeks, with variable amounts being lost in 8 weeks. Losses up to 40% were noted in the os calcis after 9 months, with essentially none in the radius and ulna. When this technique was employed during the Apollo 14, 15, and 16 missions, only one crewman (CMP Apollo 15) showed significant losses in the os calcis and none in the radius or ulna. These results were, therefore, in concert with the bed-rest data but at variance with the earlier Gemini data. The variability observed during bed rest was reconciled when it was observed that the rate of loss could be correlated with the initial 24-hour urinary hydroxyproline excretion and the initial os calcis mineral content. Prediction terms were established. Measurements of the SL-II crew after 28 days of weightlessness revealed no significant bone mineral losses. The Skylab data lie within the predicted limits obtained from the bed-rest data. The relevance of the prediction terms to the Skylab and longer missions discussed.

Absorptiometry, Photon↗

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.

Adaptation, Physiological↗

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.

Adaptation, Physiological↗

Protozoa as model systems for the study of cellular responses to altered gravity conditions.

The orientation behavior of Paramecium changed in a similar way after transition to conditions of free-fall in a sounding rocket and after transition to conditions of simulated weightlessness on a fast rotating clinostat. After a period of residual orientation, Paramecium cells distributed themselves randomly 80 s (120 s) after onset of free-fall (simulated weightlessness). Swimming velocity increased significantly; however, the increase was transient and subsided after 3 min in the rocket experiments, while the velocity remained enhanced even during 2 h of rotation on a fast clinostat. Trichocysts were present and without morphological changes in Paramecium cells which had been exposed to a rocket flight, as well as to fast or slow rotation on a clinostat. Regeneration of the oral apparatus of Stentor and morphogenesis of Eufolliculina proceeded normally on the clinostat. The results demonstrate that the clinostat is a useful tool to simulate the conditions of weightlessness on earth and to detect gravisensitive cellular functions.

Animals↗

Artificial gravity in space flight.

Clearly, physiologic adaptation to terrestrial life for all animals is assured only by frequent encounters with gravity. Indeed, upon exposure to weightlessness in space flight, losses of physiologic functions quickly begin. Some physiologic parameters change more rapidly than others, but the deconditioning process starts rapidly. The rates of functional losses for all affected parameters are interesting in that they appear to approach a limit; i.e., losses of these functions may not continue until indefinitely. The regulation of this functional asymptotic response to space is not known, but probably based on functional requirements of the body to life itself and perhaps genetic expression. The latter controlling mechanism (DNA) functions only on aquatic (weightless) animals on Earth--land animals must stimulate these physiologic functions as they relate to gravity on a regular frequent basis. This loss of regulation upon entering the weightless environment is fascinating since land-based animals including the humans have evolved from millions (perhaps billions) of years of terrestrially adapted ancestors. One would expect some DNA involvement in the regulation of its physiology, but it appears to be absent. Therefore, if the functional debilitation of space is to be denied, we must begin to understand the adaptation process of the sole basis for the control of our physiologic processes on land; i.e., how gravity regulates our biologic functions. To learn about this regulatory mechanism, some inquiry into how aquatic animals first adapted to living on land might be helpful.

Adaptation, Physiological↗

Results of medical investigations carried out on board the Salyut orbital stations.

The purpose of the medical investigations carried out in flights of the Soviet orbital station Salyut were: to further studies and clarification of the phenomenology and mechanisms of changes in the main functions of the human body during prolonged weightlessness; to accumulate additional data on human responses at an early stage of adaptation to weightlessness; to assess the effectiveness of countermeasures against adverse effects of weightlessness during and after flight. The orbital station was equipped with a set of countermeasuring devices: a trainer for physical exercises (a treadmill), gravity simulation suit for long wear, bicycle ergometer, anti-G suit to be worn immediately post-flight, drugs, etc. The system of medical control included daily recordings of electrocardiography and respiration and regular physical examinations using provocative tests (physical exercises of a known force, lower-body negative pressure). Specific biomedical investigations were performed before, during and after flight. As in previous flights, the atmosphere in the habitable modules was similar to that on the earth. Food supply met the requirements for basic nutrients and satisfied individual preferences of the crew members. In addition to the time required to fulfil the flight programme, the work-rest schedule allowed the cosmonauts 8 hours sleep, four meals, 2.5 hours physical training and personal time. The biomedical investigations carried out during and after flight furnished information towards a better understanding of human responses to the effects of space flight factors and the mechanisms underlying their development.

Adaptation, Physiological↗

A comprehensive Guyton model analysis of physiologic responses to preadapting the blood volume as a countermeasure to fluid shifts.

The Guyton model of fluid, electrolyte, and circulatory regulation is an extensive mathematical model capable of simulating a variety of experimental conditions. It has been modified for use at NASA to simulate head-down tilt, a frequently used analog of weightlessness. Weightlessness causes a headward shift of body fluids that is believed to expand central blood volume, triggering a series of physiologic responses resulting in large losses of body fluids. We used the modified Guyton model to test the hypothesis that preadaptation of the blood volume before weightless exposure could counteract the central volume expansion caused by fluid shifts, and thereby attenuate the circulatory and renal responses that result in body fluid losses. Simulation results show that circulatory preadaptation, by a procedure resembling blood donation immediately before head-down bedrest, is effective in damping the physiologic responses to fluid shifts and reducing body fluid losses. After 10 hours of head-down tilt, preadaptation also produces higher blood volume, extracellular volume, and total body water for 20 to 30 days of bedrest, compared with non-preadapted control. These results indicate that circulatory preadaptation before current Space Shuttle missions may be beneficial for the maintenance of reentry and postflight orthostatic tolerance in astronauts. This paper presents a comprehensive examination of the simulation results pertaining to changes in relevant physiologic variables produced by blood volume reduction before a prolonged head-down tilt. The objectives were to study and develop the countermeasure theoretically, to aid in planning experimental studies of the countermeasure, and to identify potentially disadvantageous physiologic responses that may be caused by the countermeasure.

Adaptation, Physiological↗

Early amphibian (anuran) morphogenesis is sensitive to novel gravitational fields.

Anuran amphibian embryos (Xenopus laevis and Rana dybowskii) are sensitive to novel gravitational fields. Under simulated weightlessness, (i) the location of the first horizontal cleavage furrow was shifted toward the vegetal pole at the eight-cell stage; (ii) the position of the blastocoel was more centered, and the number of cell layers in the blastocoel roof was increased at the blastula stage; (iii) the dorsal lip appeared closer to the vegetal pole at the gastrula stage; and (iv) head and eye dimensions were enlarged at the hatching tadpole stage. Effects of simulated hypergravity were opposite to those of simulated weightlessness, except that hypergravity, unlike simulated weightlessness, reduced the number of primordial germ cells in feeding tadpoles. Despite those dramatic differences in the early embryogenesis, tadpoles at the feeding stage are largely indistinguishable from controls.

Animals↗

Hindlimb suspension reduces muscle regeneration.

Exposure of juvenile skeletal muscle to a weightless environment reduces growth and satellite cell mitotic activity. However, the effect of a weightless environment on the satellite cell population during muscle repair remains unknown. Muscle injury was induced in rat soleus muscles using the myotoxic snake venom, notexin. Rats were placed into hindlimb-suspended or weightbearing groups for 10 days following injury. Cellular proliferation during regeneration was evaluated using 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and image analysis. Hindlimb suspension reduced (P < 0.05) regenerated muscle mass, regenerated myofiber diameter, uninjured muscle mass, and uninjured myofiber diameter compared to weightbearing rats. Hindlimb suspension reduced (P < 0.05) BrdU labeling in uninjured soleus muscles compared to weight-bearing muscles. However, hindlimb suspension did not abolish muscle regeneration because myofibers formed in the injured soleus muscles of hindlimb-suspended rats, and BrdU labeling was equivalent (P > 0.10) on myofiber segments isolated from the soleus muscles of hindlimb-suspended and weightbearing rats following injury. Thus, hindlimb suspension (weightlessness) does not suppress satellite cell mitotic activity in regenerating muscles before myofiber formation, but reduces growth of the newly formed myofibers.

Animals↗

Vestibular function in the space environment.

Adaptation to the weightless state and readaptation after space flight to the 1-G environment on the ground are accompanied by various transitory symptoms of vestibular instability, kinetosis, and illusory sensations. Aside from the problem of how to treat and if possible prevent such symptoms, they offer a clue to a better understanding of normal vestibular functions. Weightlessness is a powerful new "tool" of vestibular research. Graybiel reported as early as 1952 that human subjects observed the illusion that a real target and the visual afterimage seemed to raise in the visual field during centrifugation when the subjects were looking toward the axis of rotation (oculogravic illusion). In aircraft parabolic-flight weightlessness, human subjects observed that fixed real targets appeared to have moved downward while visual afterimages appeared to have moved upward (oculoagravic illusion). It can be shown by electronystagmography as well as by a method employing double afterimages that part of this illusion is caused by eye movements that are triggered by the changing input from the otolith system. Another part of the illusion is based on a change of the subjective horizontal and must be caused by convergence of vestibular and visual impulses "behind" the eyes. This part was measured independently of the first one by using a new method. Eye movements could be prevented during these experiments by optical fixation with the right eye on a target at the end of a 24-in. long tube which was rigidly attached parallel to the longitudinal axis of an aircraft. At the same time the subject tried to line up a shorter tube, which was pivoting around his left eye, with the subjective horizon.

Acceleration↗

Biological investigations aboard biosatellite Cosmos-782.

The Cosmos-782 flight from 25 November to 15 December 1975, carried biological experiments designed to study the effects of weightlessness on insects and fish and on gravitropism and growth in several seed varieties. Investigations carried out on Drosophila melanogaster measured the frequency of recessive lethal mutations and the change in genetic distances in the sex chromosome. The study of Fundulus heteroclitus eggs and fry compared the effects of weightlessness and artificial gravity. Plants experiments studied spatial orientation of over and underground organs of Pinus silvestris and Crepis capillaris seeds. Other investigations used Phycomyces blakesleanus to compare spatial orientation and growth and development in weightlessness and artificial gravity.

Animals↗