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PubMed1988

Biomedical support of man in space.

In its broadest sense, biomedical support of man in space must not be limited to assisting spacecraft crew during the mission; such support should also ensure that flight personnel be able to perform properly during landing and after leaving the craft. Man has developed mechanisms that allow him to cope with specific stresses in his normal habitat; there is indisputable evidence that, in some cases, the space environment, by relieving these stresses, has also allowed the adaptive mechanisms to lapse, causing serious problems after re-entry. Inflight biomedical support must therefore include means to simulate some of the normal stresses of the Earth environment. In the area of cardiovascular performance, we have come to rely heavily on complex feedback mechanisms to cope with two stresses, often combined: postural changes, which alter the body axis along which gravitational acceleration acts, and physical exercise, which increases the total load on the system. Unless the appropriate responses are reinforced continuously during flight, crew members may be incapacitated upon return. The first step in the support process must be a study of the way in which changes in g, even of short duration, affect these responses. In particular we should learn more about effects of g on the "on" and "off" dynamics, using a variety of approaches: increased acceleration on one hand at recumbency, immersion, lower body positive pressure, and other means of simulating some of the effects of low g, on the other. Once we understand this, we will have to determine the minimal exposure dose required to maintain the response mechanisms. Finally, we shall have to design stresses that simulate Earth environment and can be imposed in the space vehicle. Some of the information is already at hand; we know that several aspects of the response to exercise are affected by posture. Results from a current series of studies on the kinetics of tilt and on the dynamics of readjustment to exercise in different postures will be presented and discussed.

Adaptation, Physiological↗
PubMed1994

Teratogenic effects of gravitational changes.

In investigating the effect of gravitational changes on development, it is instructive to think of altered gravity (delta g) as a teratogen--that is, an environmental factor influencing development. Observed effects on skeletal development include: suppression of morphogenesis in centrifuged mouse limb buds; advanced fusion stages in centrifuged mouse palates; smaller crown rump lengths (CRL) and decreased number of pregnancies in centrifuged rats and mice; altered differentiation of growth plates in young growing rats in space; and decreased length of calcified long bone regions in fetal rats exposed to microgravity in utero. These studies show that delta g is able to alter development in vivo and in vitro and suggest that delta g operates, at least in part, at the cellular level.

Animals↗
PubMed1993

Myosin heavy chain expression in rodent skeletal muscle: effects of exposure to zero gravity.

This study ascertained the effects of 9 days of zero gravity on the relative (percentage of total) and calculated absolute (mg/muscle) content of isomyosin expressed in both antigravity and locomotor skeletal muscle of ground control (CON) and flight-exposed (FL) rats. Results showed that although there were no differences in body weight between FL and CON animals, a significant reduction in muscle mass occurred in the vastus intermedius (VI) (P < 0.05) but not in the vastus lateralis (VL) or the tibialis anterior. Both total muscle protein and myofibril protein content were not different between the muscle regions examined in the FL and CON groups. In the VI, there were trends for reductions in the relative content of type I and IIa myosin heavy chains (MHCs) that were offset by increases in the relative content of both type IIb and possibly type IIx MHC protein (P > 0.05). mRNA levels were consistent with this pattern (P < 0.05). The same pattern held true for the red region of the VL as examined at both the protein and mRNA level (P < 0.05). When the atrophy process was examined, there were net reductions in the absolute content of both type I and IIa MHCs that were offset by calculated increases in type IIb MHC in both VI and red VL. Collectively, these findings suggest that there are both absolute and relative changes occurring in MHC expression in the "red" regions of antigravity skeletal muscle during exposure to zero gravity that could affect muscle function.

Animals↗
PubMed1996

Tactile influences on astronaut visual spatial orientation: human neurovestibular studies on SLS-2.

Human spatial orientation in spaceflight is initially disturbed by the absence of usable graviceptor information from the otolithic organs. Experiments measuring astronaut visually induced motion (vection) strength on various flight days during the first 10 days of the Spacelab Life Sciences-2 mission demonstrated two new phenomena in addition to confirming the initial increased weighting of visual and localized tactile cues. The reliance on tactile and visual noninertial cues apparently declined after a week in space, as the crew became able to utilize their internal reference frame. Subjects also showed that even nondirectional tactile cues served as a direction anchor and inhibited visually induced roll sensation relative to a new loosely tethered test condition. Individual perceptual styles were again revealed among the four astronauts tested. The readaptation to 1 G similarly shows a period of reinterpretation of inertial and visual cues to spatial orientation. The results are discussed in terms of an internal-model representation of body orientation, with time-varying weights applied to extrinsic and intrinsic signals.

Adult↗
PubMed1996

Horizontal angular VOR changes in orbital and parabolic flight: human neurovestibular studies on SLS-2.

Further evidence was found for adaptive changes in the vestibular "velocity storage" (VS) component of the vestibuloocular reflex in four shuttle astronauts tested in parabolic flight and before, during, and after a 14-day mission. Nystagmus was recorded during and after 1 min of 120 degrees/s rotation. Gains and time constants were determined by computer analysis. Responses correlated with experience. Two subjects were making their first spaceflight. In parabolic flight, their time constants shortened to an average of 60% of 1 G values, presumably because unfamiliar otolith cues reduced VS. However, after 4-10 days in orbit, their time constants were similar or greater than those preflight, indicating VS recovery. The other two subjects had previously flown in space. Their time constants shortened in orbit to an average of 69% of 1 G values, indicating a persisting reduction of VS. This correlation with spaceflight experience has been seen in 9 of 11 subjects on 3 missions. Head pitch did not significantly "dump" nystagmus as it does on Earth.

Adult↗
PubMed1991

Changes observed in lymphocyte behavior during gravitational unloading.

The effect of microgravity has been extensively studied on human lymphocytes in several space missions. A clear distinction must be made between two kinds of experiments: (i) with cells purified from the peripheral blood of test subjects before flight and then exposed inflight to mitogens and other activators (these are called in vitro experiments), and (ii) with lymphocytes from crewmembers of space missions exposed to mitogens prior to and after flight (ex vivo experiments). The first approach can be considered as basic research in cell biology in space; the second contributes to identifying the effects of the stress of spaceflight on the immune response of astronauts. The results from in vitro experiments have clearly shown that lymphocyte activation is nearly totally depressed in microgravity. This activation depression is confirmed by investigations on Earth in the fast rotating clinostat. Conversely, activation is increased when lymphocytes are cultured at 10 g in a centrifuge. In microgravity cell adhesion may be reduced, thus partly accounting for the decreased cell activation. The results of the experiments conducted at 10 g are due to a simultaneous activation of T- and B-lymphocytes by concanavalin A. The reduced activation observed in lymphocytes from crewmembers of space missions can be ascribed to both the physical and psychological stress of spaceflight. This observation was confirmed by investigations on subjects undergoing stress on Earth.

B-Lymphocytes↗
PubMed1992

Centrifuges: evolution of their uses in plant gravitational biology and new directions for research on the ground and in spaceflight.

The use of centrifugation as a tool for exploring qualitative and quantitative features of plant responses to gravity and to other body forces can be traced to plant scientists' early 19th century experiments. To study how plants perceive and respond to gravitational stimuli requires experimental manipulation of the force or acceleration vector direction and magnitude. As technology advanced, especially during the past half-century, so did the sophistication of experimental designs and of the scientific questions that could be addressed. The most significant improvement in methodology probably will prove to be attainment of experimental access to the hypogravity range of inertial accelerations by the combination of centrifugation and spaceflight.

Acceleration↗
PubMed1994

Mechanisms of post-flight orthostatic intolerance.

Post-flight orthostatic intolerance is a dramatic physiological consequence of human adaptation to microgravity made inappropriate by a sudden return to 1-G. The immediate mechanism is almost always a failure to maintain adequate tissue perfusion, specifically perfusion of the central nervous system, but vestibular dysfunction may occasionally be the primary cause. Orthostatic intolerance is present in a wide range of clinical disorders of the nervous and cardiovascular systems. The intolerance that is produced by spaceflight and 1-G analogs (bed rest, head-down tilt at a moderate angle, water immersion) is different from its clinical counterparts by being only transiently present in subjects who otherwise have normal cardiovascular and regulatory systems. However, the same set of basic pathophysiological elements should be considered in the analysis of any form of orthostatic intolerance.

Adaptation, Physiological↗
PubMed1996

Gravitational physiology of human immune cells: a review of in vivo, ex vivo and in vitro studies.

The study of the function of immune cells in microgravity has been studied for more than 20 years in several laboratories. It is clear today that the immune system is depressed in more than 50% of the astronauts during and after space flight and that the activation of T lymphocytes by mitogens in vitro changes dramatically. This article gives an overview of the gravitational studies conducted by our laboratory in Spacelab, in MIR station, in sounding rockets and on the ground in the clinostat and the centrifuge. Three experimental approaches are followed in our work: (i) Ex vivo studies are performed with blood samples drawn from astronauts; (ii) in vivo studies are based on the application of seven antigens to the skin of the astronauts; (iii) in vitro studies are carried out with immune cells purified from the blood of healthy donors (not astronauts). The data from our in vivo and ex vivo studies are in agreement with those of other laboratories and show that the immunological function is depressed in the majority of astronauts as a consequence of the stress of space flight rather than by a direct influence of gravity on the cell. Immune depression may become a critical hazard on long duration flights on space stations or to other planets. In vitro experiments show that cultures of free-floating lymphocytes and monocytes undergo a dramatic depression of activation by the mitogen concanavalin A, while activation is more than doubled when the cells are attached to microcarrier beads. Such effects may be attributed to both direct and indirect effects of gravitational unloading on basic biological mechanisms of the cell. While the in vitro data are very important to clarify certain aspects of the biological mechanism of T cells activation, they are not descriptive of the changes of the immunological function of the astronauts.

Animals↗
PubMed1991

Tropistic responses of Avena seedlings in simulated hypogravity.

Results from investigation of the gravitropic responses of the Avena coleoptile under simulated weightlessness are presented. The tests were conducted using the flight hardware, identified by NASA as the Gravitational Plant Physiology Facility (GPPF), designed to support the Spacelab experiment, GTHRES. Weightlessness or so-called microgravity-conditions were simulated by the use of a so-called somersault clinostat. The plants were gravitropically stimulated with different g-forces and stimulation durations on a centrifuge. Timelapse video pictures of the plants were taken during the last hour prior to the stimulation and in a period of 3 hours after. The gravitropic responses of the plants were analyzed with the aid of an image analyzing system. Dose-response curves for stimulation forces 0.2, 0.4, 0.6, 0.8, and 1.0 g with different stimulation times ranging from 2 to 250 min were achieved. The results show that the reciprocity between force and stimulation time may be valid for small stimulation doses (lower than 5 g min), but not for larger doses. Furthermore, the threshold values (i.e. the smallest stimulation the plants are able to detect) found by extrapolation of the dose response curves, are less than 30 g s. The results are discussed with respect to an accepted space experiment, GTHRES, where the corresponding experiments will be carried out in the same apparatus under true microgravity conditions.

Avena↗
PubMed1996

Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells.

The white blood cell (WBC) elements and the bone marrow myeloid progenitor cell populations were analyzed to ascertain adaptation to micro-gravity and subsequent readaptation to 1 G in rats flown on the 14-day Spacelab Life Sciences-2 (SLS-2) mission. Bone marrow cells were harvested from one group of rats killed inflight (FD13) and blood was drawn from three other groups at various times. The WBC level was normal on FD14 with the exception of neutrophilia. On FD13, numbers of colony-forming units-granulocyte (CFU-G), CFU-GM, and CFU-M from flight animals were decreased compared with ground controls when incubated with recombinant rat interleukin-3 (rrIL-3) alone or in combination with recombinant human erythropoietin (rhEpo). On recovery (R + 0), flight rats had decreased numbers of total leukocytes and absolute numbers of lymphocytes and monocytes with elevated neutrophils compared with control rats. They had lower numbers of CD4, CD8, CD2, CD3, and B cells in the peripheral blood but no differences in spleen lymphocytes.

Animals↗
PubMed1988

Vestibular factors influencing the biomedical support of humans in space.

This paper will describe the biomedical support aspects of humans in space with respect to the vestibular system. The vestibular system is thought to be the primary sensory system involved in the short-term effects of space motion sickness although there is increasing evidence that many factors play a role in this complex set of symptoms. There is the possibility that an individual's inner sense of orientation may be strongly coupled with the susceptibility to space motion sickness. A variety of suggested countermeasures for space motion sickness will be described. Although there are no known ground-based tests that can predict space motion sickness, the search should go on. The long term effects of the vestibular system in weightlessness are still relatively unknown. Some preliminary data has shown that the otoconia are irregular in size and distribution following extended periods of weightlessness. The ramifications of this data are not yet known and because the data was obtained on lower order animals, definitive studies and results must wait until the space station era when higher primates can be studied for long durations. This leads us to artificial gravity, the last topic of this paper. The vestibular system is intimately tied to this question since it has been shown on Earth that exposure to a slow rotating room causes motion sickness for some period of time before adaptation occurs. If the artificial gravity is intermittent, will this mean that people will get sick every time they experience it? The data from many astronauts returning to Earth indicates that a variety of sensory illusions are present, especially immediately upon return to a 1-g environment. Oscillopsia or apparent motion of the visual surround upon head motion along with inappropriate eye motions for a given head motion, all indicate that there is much to be studied yet about the vestibular and CNS systems reaction to a sudden application of a steady state acceleration field like 1-g. From the above information it is obvious that the vestibular system does have unique requirements when it comes to the biomedical support of space flight. This is not to say that other areas such as cardiovascular, musculo-skeletal, immunological and hematological systems do not have their own unique requirements but that possible solutions to one system can provide continuing problems to another system. For example, artificial gravity might be helpful for long term stabilization of bone demineralization or cardiovascular deconditioning but might introduce a new set of problems in orientation, vestibular conflict and just plain body motion in a rotating space vehicle.

Acceleration↗
PubMed1988

Correlation of macro and micro cardiovascular function during weightlessness and simulated weightlessness.

The investigation of cardiovascular function necessarily involves a consideration of the exchange of substances at the capillary. If cardiovascular function is compromised or in any way altered during exposure to zero gravity in space, then it stands to reason that microvascular function is also modified. We have shown that an increase in cardiac output similar to that reported during simulated weightlessness is associated with a doubling of the number of post-capillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. We have developed an animal model in which to correlate microvascular and systemic cardiovascular function. The microcirculatory preparation consists of a lightweight, thermo-neutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the performed microvasculature of the cutaneous maximus muscle may be observed in the conscious, unanesthetized animal. Microcirculatory variables which may be obtained include venular and arteriolar numbers, lengths and diameters, single vessel flow velocities, vasomotion, capillary hematocrit anastomoses and orders of branching. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and arterial and venous pressures allows correlation of macro- and microcirculatory changes at the same time, in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total cardiovascular function may be obtained in the same animal without the complicating influence of anesthetics.

Animals↗
PubMed1994

Pituitary cells in space.

Cells of the mammalian pituitary gland synthesize and secrete several protein hormones which regulate a number of organ systems throughout the body. These include the musculoskeletal, immune, vascular and endocrine systems. Since changes occur in these tissues as a result of spaceflight, and since pituitary growth hormone (GH) and prolactin (PRL) play a role in the control of these systems on earth, we have focused attention over the last 10 years on GH and PRL cell function during and after spaceflight. The cumulative results of 4 spaceflight missions and several mimicked microgravity experiments establish 1) that production and release of biologically active GH and PRL is repeatedly and significantly attenuated (usually > 50%) and 2) that changes in cell morphology also occur. In this paper we describe our results within the framework of methodologies and approaches frequently used to study pituitary cell function on earth. In so doing we hope to develop future flight experiments aimed at uncovering possible microgravity "sensing systems" within the pituitary cell.

Animals↗
PubMed1997

Psychosocial value of space simulation for extended spaceflight.

There have been over 60 studies of Earth-bound activities that can be viewed as simulations of manned spaceflight. These analogs have involved Antarctic and Arctic expeditions, submarines and submersible simulators, land-based simulators, and hypodynamia environments. None of these analogs has accounted for all the variables related to extended spaceflight (e.g., microgravity, long-duration, heterogeneous crews), and some of the stimulation conditions have been found to be more representative of space conditions than others. A number of psychosocial factors have emerged from the simulation literature that correspond to important issues that have been reported from space. Psychological factors include sleep disorders, alterations in time sense, transcendent experiences, demographic issues, career motivation, homesickness, and increased perceptual sensitivities. Psychiatric factors include anxiety, depression, psychosis, psychosomatic symptoms, emotional reactions related to mission stage, asthenia, and postflight personality, and marital problems. Finally, interpersonal factors include tension resulting from crew heterogeneity, decreased cohesion over time, need for privacy, and issues involving leadership roles and lines of authority. Since future space missions will usually involve heterogeneous crews working on complicated objectives over long periods of time, these features require further study. Socio-cultural factors affecting confined crews (e.g., language and dialect, cultural differences, gender biases) should be explored in order to minimize tension and sustain performance. Career motivation also needs to be examined for the purpose of improving crew cohesion and preventing subgrouping, scapegoating, and territorial behavior. Periods of monotony and reduced activity should be addressed in order to maintain morale, provide meaningful use of leisure time, and prevent negative consequences of low stimulation, such as asthenia and crew member withdrawal. Leadership roles and lines of authority need to be studied further to understand the factors leading to status leveling, leadership competition, and role confusion. Finally, the relationship between crews and ground personnel should be characterized in order to minimize the displacement of anger and tension to the outside, to counter the effects of inter-group miscommunications, and to develop support strategies that can help to counter in-group/out-group conflicts. Ground-based space simulations still have a role to play in terms of understanding the impact of these factors and ways of dealing with them. In particular, issues involving language, cultural differences, gender biases, career motivation, monotonous conditions, use of free time, leadership, lines of authority, and the relationship between crews and outside monitoring personnel need to be further characterized and examined under controlled conditions. Until such time as these factors can be studied directly in space, simulations provide an opportunity to learn more about these psychosocial issues and to plan ways of minimizing their negative consequences during actual space missions.

Career Choice↗