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Is there resetting of central venous pressure in microgravity?

In the early phase of the Space Shuttle program, NASA flight surgeons implemented a fluid-loading countermeasure in which astronauts were instructed to ingest eight 1-g salt tablets with 960 ml of water approximately 2 hours prior to reentry from space. This fluid loading regimen was intended to enhance orthostatic tolerance by replacing circulating plasma volume reduced during the space mission. Unfortunately, fluid loading failed to replace plasma volume in groundbased experiments and has proven minimally effective as a countermeasure against post-spaceflight orthostatic intolerance. In addition to the reduction of plasma volume, central venous pressure (CVP) is reduced during exposure to actual and groundbased analogs of microgravity. In the present study, we hypothesized that the reduction in CVP due to exposure to microgravity represents a resetting of the CVP operating point to a lower threshold. A lower CVP 'setpoint' might explain the failure of fluid loading to restore plasma volume. In order to test this hypothesis, we conducted an investigation in which we administered an acute volume load (stimulus) and measured responses in CVP, plasma volume and renal functions. If our hypothesis is true, we would expect the elevation in CVP induced by saline infusion to return to its pre-infusion levels in both HDT and upright control conditions despite lower vascular volume during HDT. In contrast to previous experiments, our approach is novel in that it provides information on alterations in CVP and vascular volume during HDT that are necessary for interpretation of the proposed CVP operating point resetting hypothesis.

Aerospace Medicine↗

Response of the neuromuscular unit to spaceflight: what has been learned from the rat model.

Despite the inherent limitations placed on spaceflight investigations, much has been learned about the adaptations of the neuromuscular system to weightlessness from studies of rats flown for relatively short periods (approximately 4-22 days). Below is a summary of the major effects of spaceflight observed in muscles of rats that are not in their rapid growth stage: 1. Skeletal muscles atrophy rapidly during spaceflight; significant atrophy is observed as early as after 4 days of flight. 2. The atrophic response appears to be related to the primary function of the muscle. In the hindlimb, the relative amount of atrophy can be characterized as slow extensors > fast extensors > fast flexors. This pattern of relative atrophy does not appear to be occurring in the forelimb; however, not enough data are available to draw any definitive conclusions at this time. 3. Both slow and fast fibers atrophy during spaceflight, with the largest fibers within an individual muscle generally showing the greatest atrophic response. Interestingly, the amount of fiber atrophy appears to reach a plateau after about 14 days of flight. 4. Adaptations have been observed in the concentration and content of all muscle proteins pools, with the protein pools in slow muscles the most affected. 5. Some slow and fast fibers in predominantly slow and fast muscles show shifts in their histochemical and biochemical properties, toward those observed in a "faster" phenotype. 6. Some fibers, presumably expressing slow MHC isoforms before flight, begin to express fast MHC isoforms during flight. 7. The oxidative capacity of the muscles or fibers is relatively unaffected by spaceflight, particularly in the slow muscles. Any change in whole-body fatigability associated with spaceflight most likely reflects the loss in muscle and fiber mass. 8. The glycolytic capacity of the muscles and muscle fibers is enhanced after spaceflight. This metabolic adaptation seems to be related to the shift in the contractile proteins towards "faster" isoforms. 9. The vascularity of muscles appears to be maintained after flight, based, at least, on histological observations of capillarity. 10. The force capabilities of the muscles and fibers appear to decrease in parallel with the decreases in size, i.e., the specific tension is not significantly affected after flight. 11. Changes in the speed-related properties of the slow muscles are consistent with the adaptations in the myosin molecule, i.e., the slow muscles and some fibers in the slow muscles become "faster." 12. Some muscle fiber and neuromuscular junction damage has been observed after flight, particularly in the slow muscles. The extent of damage may be related to the amount of time that the muscles are allowed to reload before removal, i.e., in general, shorter intervals result in less fiber damage. 13. Adaptations in the motor (ventral horn) and sensory (spinal ganglia) neurons have been quite variable, but this may be related to the amount of time that the muscles are allowed to reload before removal. Morphological adaptations after relatively short periods of reloading may reflect a decrease in the activation of the neural elements during flight.

Adaptation, Physiological↗

Spacelab Life Sciences flight experiments: an integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension.

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO2 and C2H2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be obtained. The central venous catheter will be inserted immediately pre-launch and monitored with heart rate and blood pressure in-flight until cardiac output, respiratory gas exchange and quantitative 2D echocardiography measurements can be performed. In-flight hemodynamic measurements will be repeated at rest and during submaximal exercise daily and also during maximal exercise midway through the flight to document the timecourse and extent of cardiovascular changes in the payload crew. Parallel studies are planned for the animals. In addition to measurements of right atrial and aortic pressures and cardiac output, a dorsal micro-circulatory chamber will allow determinations of changes in capillary and venular architecture and function in six of the rats. The techniques and findings from many of the SLS-1 and 2 supporting studies have already yielded significant information about circulatory regulation in patients with both hypo- and hypertension. The flight experiments themselves will provide new data to test the validity of both animal and human models currently used for simulating the fluid shifts of a micro-gravity environment. The development of effective countermeasures, not only for short and long duration space travellers, but also for Earth-bound medical patients can then be physiologically based on experimental data rather than anecdote.

Animals↗

Cardiovascular response to submaximal exercise in sustained microgravity.

Cardiac output (Q), heart rate (HR), blood pressure, and oxygen consumption (VO2) were measured repeatedly both at rest and at two levels of exercise in six subjects during microgravity exposure. Exercise was at 30 and 60% of the workload producing the individual's maximal VO2 in 1 G. Three of the subjects were on a 9-day flight, Spacelab Life Sciences-1, and three were on a 15-day flight, Spacelab Life Sciences-2. We found no temporal differences during the flights. Thus we have combined all microgravity measurements to compare in-flight values with erect or supine control values. At rest, Q in flight was 126% of Q erect (P < 0.01) but was not different from Q supine, and HR in flight was 81% of HR erect (P < 0.01) and 91% of HR supine (P < 0.05). Thus resting stroke volume (SV) in flight was 155% of SV erect (P < 0.01) and 109% SV supine (P < 0.05). Resting mean arterial blood pressure and diastolic pressure were lower in flight than erect (P < 0.05). Exercise values were considered as functions of VO2. The increase in Q with VO2 in flight was less than that at 1 G (slope 3.5 vs. 6.1 x min-1.l-1.min-1). SV in flight fell with increasing VO2, whereas SV erect rose and SV supine remained constant. The blood pressure response to exercise was not different in flight from erect or supine. We conclude that true microgravity causes a cardiovascular response different from that seen during any of its putative simulations.

Adult↗

Diet and nitrogen metabolism during spaceflight on the shuttle.

Human spaceflight is associated with a loss of body protein. To investigate this problem, dietary intake, nitrogen balance, the whole body protein, and fibrinogen protein synthesis rates were measured on the crews of two Spacelab Life Sciences (SLS) shuttle missions before, during, and after spaceflight. The first mission, SLS-1, lasted 9.5 days, and the second, SLS-2, lasted 15 days. The 15N-glycine method was used for the protein synthesis measurements. The following results were obtained. 1) There was a rapid decline in weight for the first 5 days and then the body weight appeared to stabilize. 2) The mean energy intake preflight was 39.0 +/- 2.5 kcal x kg-1 x day-1 (n = 10). There was a sharp drop in dietary intake on flight day 1, with recovery by the second day, and then energy intake was constant at 30.4 +/- 1.5 kcal x kg-1 x day-1 (n = 12) for the remainder of the flight period (P < 0.05). 3) Nitrogen retention was decreased during flight, with the magnitude of the decrease lessening toward the end of the mission. The daily mean nitrogen balance changed from 58 +/- 9 mg x kg-1 x day-1 (n = 9) preflight to 16 +/- 3 mg N x kg-1 x day-1; P < 0.05; n = 11) in flight, corresponding to a loss of approximately 1 kg of lean body mass over 14 days. 4) Whole body protein synthesis was increased early in flight and on recovery, as was fibrinogen synthesis. We conclude that 1) the rapid readjustment and stabilization of energy intake and the improved nitrogen retention with increasing flight duration are consistent with a rapid metabolic accommodation to the novel environment; and that 2) the increased protein turnover indicates that a metabolic stress response is an important factor in this adjustment process.

Adult↗

The effects of space flight on the contractile apparatus of antigravity muscles: implications for aging and deconditioning.

Previous studies have shown that the unloading of skeletal muscle, as occurring during exposure to space flight, exerts a profound effect on both the mass (cross sectional area) of skeletal muscle fibers and the relative expression of protein isoforms comprising the contractile system. Available information suggests that slow (type I) fibers, comprising chiefly the antigravity muscles of experimental animals, in addition to atrophying, undergo alterations in the type of myosin heavy chain (MHC) expressed such that faster isoforms become concomitantly expressed in a sub-population of slow fibers when insufficient force-bearing activity is maintained on the muscle. Consequently, these transformations in both mass and myosin heavy chain phenotype could exert a significant impact on the functional properties of skeletal muscle as manifest in the strength, contractile speed, and endurance scope of the muscle. To further explore these issues, a study was performed in which young adult male rats were exposed to zero gravity for six days, following which, the antigravity soleus muscle was examined for a) contractile properties, determined in situ and b) isomyosin expression, as studied using biochemical, molecular biology, and histochemical/immunohistochemical techniques.

Aging↗

Functional and cellular adaptations of rodent skeletal muscle to weightlessness.

Microgravity perturbs a wide variety of physiological systems. Specifically, skeletal muscle has been shown to undergo dramatic changes even during spaceflights of short durations. Despite a growing body of knowledge, many critical issues related to sarcomeric gene expression and the translation of this information into muscle function remain relatively unexplored. Ultimately, the types and quantities of contractile proteins present in skeletal muscle fibers determine muscle function. As shown in Figure 1, the pool of contractile proteins is determined by 4 important processes: i) transcription of sarcomeric genes; ii) translation of sarcomeric mRNA transcripts; iii) myofibrillar assembly; and iv) myofibrillar disassembly (i.e., protein degradation). Any factor(s) affecting one or more of these systems will ultimately impact skeletal muscle function. With respect to Figure 1, the objective of this paper is to provide a focused summary of the affects of short duration spaceflights on myosin composition of the soleus (SOL) muscle. This will be achieved by describing the affects of spaceflight upon: i) mechanical properties of skeletal muscle that are determined by the types and quantity of myosin; ii) myosin heavy chain (MHC) protein isoform composition; and ii) MHC mRNA isoform content. Data reported in this paper are from spaceflight missions having durations of 6 (PARE-02;2) and 14 days (SLS-2).

Animals↗

Dynamic cell culture system: a new cell cultivation instrument for biological experiments in space.

The prototype of a miniaturized cell cultivation instrument for animal cell culture experiments aboard Spacelab is presented (Dynamic cell culture system: DCCS). The cell chamber is completely filled and has a working volume of 200 microliters. Medium exchange is achieved with a self-powered osmotic pump (flowrate 1 microliter h-1). The reservoir volume of culture medium is 230 microliters. The system is neither mechanically stirred nor equipped with sensors. Hamster kidney (Hak) cells growing on Cytodex 3 microcarriers were used to test the biological performance of the DCCS. Growth characteristics in the DCCS, as judged by maximal cell density, glucose consumption, lactic acid secretion and pH, were similar to those in cell culture tubes.

Animals↗

Bioprocessing under microgravity--an introduction.

The main biological processes presently considered for applications in space laboratories are: (i) bioseparation, (ii) cell cultivation and (iii) cell electrofusion. All three technologies were discussed by experts in the field at the 1988-COSPAR Meeting in Helsinki.

Biotechnology↗

Mammalian cell cultivation in space.

Equipment used in space for the cultivation of mammalian cells does not meet the usual standard of earth bound bioreactors. Thus, the development of a space worthy bioreactor is mandatory for two reasons: First, to investigate the effect on single cells of the space environment in general and microgravity conditions in particular, and second, to provide researchers on long term missions and the Space Station with cell material. However, expertise for this venture is not at hand. A small and simple device for animal cell culture experiments aboard Spacelab (Dynamic Cell Culture System; DCCS) was developed. It provides 2 cell culture chambers, one is operated as a batch system, the other one as a perfusion system. The cell chambers have a volume of 200 microliters. Medium exchange is achieved with an automatic osmotic pump. The system is neither mechanically stirred nor equipped with sensors. Oxygen for cell growth is provided by a gas chamber that is adjacent to the cell chambers. The oxygen gradient produced by the growing cells serves to maintain the oxygen influx by diffusion. Hamster kidney cells growing on microcarriers were used to test the biological performance of the DCCS. On ground tests suggest that this system is feasible.

Animals↗

Theories and models of the biology of the cell in space--an introduction.

The World Space Congress 1992 took place after two Spacelab flights with important biological payloads on board, the SLS-1 (June 1991) and IML-1 (January 1992) missions respectively. Interesting experiments were carried out in 1991 also on the Shuttle middeck and on the sounding rocket MASER 4. The highlights of the investigations on these missions together with the results of relevant ground-based research were presented at the symposium.

Animals↗

Absence of a growth hormone effect on rat soleus atrophy during a 4-day spaceflight.

The objectives of the present study were to determine the size and enzyme properties of soleus fibers of rats subjected to a 4-day spaceflight (National Aeronautics and Space Administration, STS-41) and the effects of exogenous growth hormone (GH) on the atrophic response of the muscle. Four groups of rats were studied: 1) control (Con), 2) Con plus GH treated (Con + GH), 3) flight (Fl), and 4) F1 plus GH treated (Fl + GH). Cross-sectional area and the activities of succinate dehydrogenase and myofibrillar adenosinetriphosphatase (ATPase) were determined in fibers identified in frozen serial cross sections. Fibers were categorized immunohistochemically as slow, fast, or slow-fast on the basis of their reaction with slow and fast myosin heavy-chain (MHC) monoclonal antibodies. Fibers also were categorized as light or dark on the basis of their staining for ATPase at pH 8.6. After the 4-day flight, mean body weight was significantly decreased compared with control. The absolute and relative (muscle wt/body wt) soleus weights were significantly smaller in the Fl and Fl + GH rats compared with their respective ground-based controls. In both flight groups, the cross-sectional area of the light ATPase fibers was significantly smaller (approximately 30%) than control. Three of 11 flight rats had a higher proportion of fibers expressing both slow and fast MHCs than expected on the basis of the fiber type distribution in the 11 control rats. Mean fiber succinate dehydrogenase and ATPase activities were similar among the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

Cultivation of single cells in space.

The purpose of this review is to present an updated and comprehensive analysis of the experiments with single cells performed in space. Especially the results of the investigations performed in Biorack on the D-1 mission clearly show that important cellular functions are changing in microgravity. Cell proliferation, differentiation, metabolism, membrane properties, and cytoplasmic streaming underwent significant alteration during exposure to space flight conditions in a variety of single cells cultures spanning from bacteria to mammalian cells. These findings open new and interesting perspectives to basic and applied research in microgravity. The focus of this paper is on the cultivation of mammalian cells in space laboratories and on the related instrumentation. While Biorack is a useful and efficient instrument for simple studies in Spacelab, the development of new facilities like incubators with automated fixation devices as well as of more complex bioreactors is strongly recommended.

Animals↗

Use of bed rest and head-down tilt to simulate spaceflight-induce immune system changes.

Bed rest, both with and without head-down tilt, has been extensively used as an earth-bound analog to study physiologic effects mimicking those occurring in weightlessness during spaceflight. We have been able to show in six subjects that 4 weeks of head-down tilt bed rest induces a significant decrease in interleukin-2 secretion by PHA-stimulated T lymphocytes. Another study, lasting 113 days, with two subjects showed a decreased interleukin-2 receptor expression in PHA-stimulated peripheral blood mononuclear cells but a decreased interleukin-2 production in one subject only. Under the same conditions, interleukin-1 production was largely increased in both subjects. Several other immune parameters were also analyzed. Increased interleukin-1 production could contribute to bone mineral loss encountered during bed rest and decreased interleukin-2 secretion could play a role in the appearance of infectious diseases often observed during bed red.

Antibody Formation↗

Myosin heavy chain isoforms of human muscle after short-term spaceflight.

The influence of microgravity on the myosin phenotype of skeletal muscle fibers in the vastus lateralis of eight crew members was studied before and after 5-day (n = 3) and 11-day (n = 5) spaceflights (space shuttle flights: STS-32, -33 and -34). Single-fiber electrophoresis analyses showed that the proportion of fibers expressing only slow (type I) myosin heavy chain (MHC) in the vastus lateralis was significantly lower after than before 11 days of spaceflight. Although the family of type II MHC isoforms was elevated post- compared with preflight, the distribution among the isoforms of type II MHC was not statistically different. Based on monoclonal and polyclonal antibodies specific for three adult MHC isoforms and single-fiber electrophoresis, approximately 3% of the fibers analyzed coexpressed all three adult MHC isoforms. The results from immunohistochemical staining with two different sets of antibodies indicate a reduction in the percentage of fibers expressing type I MHC as a result of spaceflight. The mean difference, however, was significant only when the fibers were categorized simply as type I or II. These changes appeared to be highly individualized among the astronauts. These results suggest that a rapid change in MHC isoform expression can occur in some muscle fibers after a relatively brief exposure to spaceflight.

Adult↗