Prediction of human orthostatic tolerance by changes in arterial and venous hemodynamics in the microgravity environment

In this article, we intentionally present exclusively the results of our recent studies of arterial and venous hemodynamics as predictors of human orthostatic tolerance during space flight and after the return to Earth. The possibility of in-flight orthostatic tolerance prediction by arterial hemodynamic responses to the lower body negative pressure (LBNP) and venous hemodynamic changes in response to occlusion of the lower extremities is demonstrated. For the first time, three levels of cerebral blood flow deficits during the determination of orthostatic tolerance in the course of the LBNP test performed in microgravity. We offer quantitative arguments for the dependence of the cerebral blood flow deficit on the degree of tolerance of the LBNP test. Patterns of arterial hemodynamics during LBNP were successfully used to diagnose the actual orthostatic tolerance and to follow its trend during flight, which testifies to the possibility of predicting orthostatic tolerance changes in an individual cosmonaut during space flight. Occlusion plethysmography of the legs revealed three levels of response of the most informative venous parameters (capacity, distensibility, and rate of filling) of the lower extremities correlated to the severity of decrease in orthostatic tolerance.     

Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures

The development of orthostatic hypotension and instability immediately after return from spaceflight has been a significant operational problem to astronauts for more than four decades. Significant reductions in stroke volume and peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with reduced circulating blood volume, although cardiac atrophy might also contribute. Space flight and ground based experiments have demonstrated that an inability to provide adequate peripheral vasoconstriction in astronauts that become presyncopal may be associated with several mechanisms including reduced sympathetic nerve activity, arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta-adrenergic receptors, etc. In addition, an inability to provide adequate tachycardia in presyncopal subjects may be associated with reduced carotid-cardiac baroreflex sensitivity. Based on the current knowledge and understanding of cardiovascular mechanisms that are altered during exposure to microgravity, a major focus of future research should be directed to the systematic evaluation of potential countermeasures that specifically target and restore the function of these mechanisms. Based on a preliminary systematic evaluation presented in this review, acute physical exercise designed to elicit maximal effort, G-suit inflation, artificial gravity, and specific pharmacological interventions, alone or in combination, have shown promise as successful countermeasures that provide protection against post-flight orthostatic intolerance.     

Mechanisms of postspaceflight orthostatic hypotension: low alpha1-adrenergic receptor responses before flight and central autonomic dysregulation postflight

Although all astronauts experience symptoms of orthostatic intolerance after short-duration spaceflight, only approximately 20% actually experience presyncope during upright posture on landing day. The presyncopal group is characterized by low vascular resistance before and after flight and low norepinephrine release during orthostatic stress on landing day. Our purpose was to determine the mechanisms of the differences between presyncopal and nonpresyncopal groups. We studied 23 astronauts 10 days before launch, on landing day, and 3 days after landing. We measured pressor responses to phenylephrine injections; norepinephrine release with tyramine injections; plasma volumes; resting plasma levels of chromogranin A (a marker of sympathetic nerve terminal release), endothelin, dihydroxyphenylglycol (DHPG, an intracellular metabolite of norepinephrine); and lymphocyte beta(2)-adrenergic receptors. We then measured hemodynamic and neurohumoral responses to upright tilt. Astronauts were separated into two groups according to their ability to complete 10 min of upright tilt on landing day. Compared with astronauts who were not presyncopal on landing day, presyncopal astronauts had 1). significantly smaller pressor responses to phenylephrine both before and after flight; 2). significantly smaller baseline norepinephrine, but significantly greater DHPG levels, on landing day; 3). significantly greater norepinephrine release with tyramine on landing day; and 4). significantly smaller norepinephrine release, but significantly greater epinephrine and arginine vasopressin release, with upright tilt on landing day. These data suggest that the etiology of orthostatic hypotension and presyncope after spaceflight includes low alpha(1)-adrenergic receptor responsiveness before flight and a remodeling of the central nervous system during spaceflight such that sympathetic responses to baroreceptor input become impaired.     

Morphogenesis and cell wall changes in maize shoots under simulated microgravity conditions.

Various plant organs show a spontaneous curvature on a three-dimensional clinostat. Changes in the cell wall metabolism underlying the curvature were examined in maize shoots. In coleoptile nodes, no differences were detected in either the level or the composition of cell wall polysaccharides between the convex and the concave halves. However, the convex side showed a higher activity of (1 --> 3),(l --> 4)-beta-glucan breakdown, which appears to be associated with the curvature. In the elongating region of coleoptiles, the accumulation of wall polysaccharides occurred in the convex side. There was no significant difference in the glucanase activity between both sides. Thus, the spontaneous curvature in different regions of maize shoots may be brought about through different mechanisms under simulated microgravity conditions.     

Redistribution of bodily fluids under conditions of microgravity and in microgravity models

This review is focused on the redistribution of blood and other bodily fluids along the body axis in the cranial direction under conditions of microgravity or during simulation of the physiological effects of microgravity. This redistribution of bodily fluids in the direction of the thorax or head results in respective physiological responses and induces a whole cascade of secondary adaptation mechanisms. Changes in central venous pressure, heart cavity volume, kidney functioning, and hormonal volume regulation lead to adaptive modifications in bodily fluid sectors. Modification of the hemodynamic in the splanchnic vascular system influences the organs of the abdominal cavity. Pharmacological correction accelerates the adaptation of the human body to unusual living conditions.     

Cell wall changes involved in the automorphic curvature of rice coleoptiles under microgravity conditions in space

Seedlings of rice (Oryza sativa L. cv. Koshihikari and cv. Tan-ginbozu) were cultivated on board the Space Shuttle STS-95 mission and changes in the morphology and the cell wall properties of coleoptiles were analyzed. In space, rice coleoptiles showed a spontaneous (automorphic) curvature toward the caryopsis in the elongating region. The angle of automorphic curvature was larger in Koshihikari than in a gibberellin-deficient dwarf cultivar, Tan-ginbozu, and the angle gradually decreased during the growth of coleoptiles in both cultivars. The more quickly expanding convex side of the bending region of the rice coleoptiles showed a greater extensibility of the cell wall than the opposite side. There was a significant correlation between the angle of curvature and the difference in the cell wall extensibility between the convex and the concave sides. Both the levels of the cell wall polysaccharides per unit length of coleoptile and the ratio of high-molecular-mass polysaccharides in the hemicellulose fraction were lower in the convex side than the concave one. Also, the activity of (13),(14)--glucanases in the cell wall was higher in the convex side than the concave one. These results suggest that the uneven modifications of cell wall metabolism bring about the difference in the levels and the molecular size of the cell wall polysaccharides, thereby causing the difference in capacity of the cell wall to expand between the dorsal and the ventral sides, leading to the automorphic curvature of rice coleoptiles in space. The data also suggest the involvement of gibberellins in inducing the automorphic curvature under microgravity conditions.     

Cytoskeleton structure and adhesion properties of human stromal precursors under conditions of simulated microgravity

During spaceflight and in simulated microgravity (SMG), cytoskeleton rearrangements were observed in lymphocytes, glial cells and osteoblasts. One potential mechanism for the cytoskeletal gravisensitivity of cells is the disruption of the extracellular matrix and integrin interactions. We investigated the effect of SMG on the structure of the actin cytoskeleton, distribution of cellular vinculin, the expression of some integrin subtypes and cellular adhesion molecules in cultured mesenchymal stem cells (hMSCs) derived from human bone marrow in vitro. Simulated microgravity was produced by desktop RPM equipment (Dutch Space, Netherlands). Cells were exposed to simulated microgravity for 30 min to 120 h. The results showed that the actin cytoskeleton was reorganized very quickly (30 min). Later (6, 24, and 48 h), the number of cells with disrupted actin cytoskeletons was increased; however, after 120 h of exposure, cells partly regained their F-actin structures. RPM exposure augmented the number of cells that express integrin-α2. We also observed a decrease in the number of VCAM-1-positive cells and changes in the expression of ICAM-1. Our findings indicate that SMG induces reversible microfilament reorganization in hMSCs and alters their adhesion properties.     

Automorphogenesis of maize roots under simulated microgravity conditions

Plant seedlings show exaggerated growth responses on a three-dimensional clinostat. Such an automorphogenesis appears to be one of major factors which govern the life cycle of higher plants under a microgravity environment. On the three-dimensional clinostat, maize roots exhibited curvatures in three different portions; 1) the basal region just protruding from the coleorhiza, 2) the region between the mature and the elongation zone, and 3) the elongation zone, several mm from the tip. Even non-clinostatted control roots showed some degree of curvature. The curvature occurred at random without any dorsiventrality. There was no difference in the osmotic concentration of the cell sap between the convex and the concave halves of any region. However, the convex, rapidly expanding side exhibited a higher extensibility of the cell wall in some regions, which appears to be a cause of the curvature. In order to understand the role of gravity in regulation of plant growth and development, we should clarify a series of events by which an automorphogenesis is induced under simulated microgravity conditions.     

Growth regulation mechanisms in higher plants under microgravity conditions - changes in cell wall metabolism.

During Space Shuttle STS-95 mission, we cultivated seedlings of rice (Oryza sativa L. cv. Koshihikari and cv. Tan-ginbozu) and Arabidopsis (Arabidopsis thaliana L. cv. Columbia and cv. etr1-1) for 68.5, 91.5, and 136 hr on board, and then analyzed changes in the nature of their cell walls, growth, and morphogenesis under microgravity conditions. In space, elongation growth of both rice coleoptiles and Arabidopsis hypocotyls was stimulated. Also, the increase in the cell wall extensibility, especially that in the irreversible extensibility, was observed for such materials. The analyses of the amounts, the structure, and the physicochemical properties of the cell wall constituents indicated that the decreases in levels and molecular masses of cell wall polysaccharides were induced under microgravity conditions, which appeared to contribute to the increase in the wall extensibility. The activity of certain wall enzymes responsible for the metabolic turnover of the wall polysaccharides was increased in space. By the space flight, we also confirmed the occurrence of automorphogenesis of both seedlings under microgravity conditions; rice coleoptiles showed an adaxial bending, whereas Arabidopsis hypocotyls elongated in random directions. Furthermore, it was shown that spontaneous curvatures of rice coleoptiles in space were brought about uneven modifications of cell wall properties between the convex and the concave sides.     

Plasticity of arterial vasculature during simulated weightlessness and its possible role in the genesis of postflight orthostatic intolerance

Even after several decades of extensive research, the basic mechanism of postflight cardiovascular dysfunction has not yet been fully elucidated. It is now well recognized that multiple mechanisms might account for the frequent occurrence of significant postflight orthostatic intolerance. It has been found that all tissues adapt their design when exposed to sustained alteration in local activity and/or stress. The most obvious example is the musculo-skeletal system, structure and function of which might be severely affected during microgravity exposure. In an attempt to elucidate whether structure and function of cardiac and vascular smooth muscle might be affected by simulated by microgravity, a serial work was started several years ago. In this paper, we present our more recent findings on plasticity of arterial vasculature and its innervation state during and after simulated microgravity and its time course.     

Repair of cellular radiation damage in space under microgravity conditions

The influence of microgravity on the repair of x-ray-induced DNA double-strand breaks was studied in the temperature-conditional repair mutant rad54–3 of diploid yeast Saccharomyces cerevisiae. Cells were exposed on the ground and kept at a low temperature until microgravity conditions were achieved. In orbit, they were incubated at the permissive temperature to allow repair. Before re-entry they were again cooled down and kept at a low temperature until final analysis. The experiment, which was flown on the shuttle Atlantis on flight STS-76 (SMM-03), showed that repair of pre-formed DNA double-strand breaks in yeast is not impaired by microgravity. Received: 1 September 1998 / Accepted in revised form: 23 March 1999