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Intracranial pressure in microgravity conditions: non-invasive assessment by ophthalmodynamometry.

BACKGROUND: As well known from former manned spaceflight experiments (German D2-Mission/German D1-Mission 1985/German-Russian MIR-Mission 1 992/German-D2-Mission 1993), fluid shift after entry into microgravity leads to a rapid increase in pressure and volume within the upper compartments of the human body. This has been proven by precise measurements with automatic selftonometers for intraocular pressure. HYPOTHESIS: There is little doubt, that a very similar--even more, marked--increase of intracranial pressure happens soon after entry into microgravity. This may be the cause for some of the reported hormonal and even neurological changes in metabolism. There is no non-invasive method to assess these important increases in pressure. METHODS: Ophthalmodynamometry in general allows for rather precise estimation of intracranial BP, but so far the method was too complicated for routine application, specifically in spaceflight conditions. Therefore, using the microprocessor controlled technology of our automatic selftonometer we have designed a very precise automatic instrument which can be applied by the astronaut/kosmonaut. The measurement takes only a few seconds. CONCLUSIONS: This easily applied, non-invasive method would allow for completely new insights into these important changes and explain some of the clinical consequences noted so far.

Astronauts↗

Unloading does not increase brown-adipose-tissue activity in rat pups.

Our previous study has shown that chronic hindlimb suspension leads to an increase in both the thermogenic capacity and the activity in brown adipose tissue (BAT) of adult rats (Yamashita, H., Ohira, Y., Wakatsuki, T., Yamamoto, M., Kizaki, T., Oh-ishi, S., Sato, Y. and Ohno, H. (1995). J. Appl. Physiol. 78: 384-387). In order to examine if unloading also increases the BAT activity in rat pups, the hindlimbs in the suspended pups were unloaded by tail suspension beginning on postnatal day 4 and suspended until day 21. The thermogenic activity (which was assessed by guanosine 5'-diphosphate binding to BAT mitochondria) was markedly lower in 21-day-old suspended pups than in 21-day-old control pups, although there was no difference in uncoupling protein 1 (UCP1) content or UCP1 mRNA expression in the BAT mitochondrial fraction between both pups. Likewise, there was no disparity in either adrenal or thymus mass between the control and suspended pups throughout the experiment. These results suggest that, in contrast to adult rats, chronic hindlimb suspension leads to a decrease in the thermogenic activity in BAT of rat pups possibly for reason that pups are less susceptible to the stress of unloading.

Adipose Tissue, Brown↗

Effects of hindlimb suspension and elevated ambient CO2 on rat growth and renal function.

BACKGROUND: Previous studies show that an ambient CO2 concentration of 2.0% may complicate interpretation of animal experiments conducted in spaceflight, while 0.7% CO2 exposure produces minimal effects. HYPOTHESIS: With additional spaceflight factors, such as microgravity, effects from the 0.7% CO2 exposure may be amplified. METHODS: To investigate the combined effects from microgravity and elevated CO2 on growth and renal function, two groups of rats were hindlimb suspended for 37 d, and a third group served as an ambulatory vivarium control (AMB). One suspension group was exposed to 0.7% CO2 for 30 d (HLS + 0.7% CO2), while the other group (HLS) served as a suspended control. Both the AMB and HLS groups breathed room air at 0.03% CO2. RESULTS: The HLS group showed responses consistent with past hindlimb suspension studies when compared with AMB, indicating similar reductions in organ and tissue weights and body weight gain. When comparing HLS + 0.7% CO2 animals to HLS controls, exposure to CO2 revealed lowered food consumption and increased urine volume, NH3 and CO2 excretion, with no differences in any of the other measured parameters, such as body weight gain, pH values, or electrolyte handling. CONCLUSION: This study shows that chronic exposure to both 0.7% ambient CO2 and hindlimb suspension together have little additional effect on rat growth and renal function.

Air Pollution, Indoor↗

Continuous monitoring of change in hemodilution during water immersion in humans: effect of water temperature.

BACKGROUND: The present study was designed to examine whether water temperature during head-out immersion (HOI) modifies hemodilution dynamics. METHODS: We made continuous measurements of blood density (rho(b)) during HOI at 3 different water temperatures; the lower critical (32 degrees C), neutral (34.5 degrees C), and upper critical (36 degrees C) temperatures in 6 healthy male volunteers. Blood was withdrawn continuously from the antecubital vein for measurement of rho(b) during 60 min of water immersion with a 10-min control period before the immersion. The density was measured with the mechanical oscillator technique. Hematocrit (Hct), plasma density (rho(p)), and osmolality were measured at 5-min intervals. Erythrocyte density (rho(e)) was calculated from rho(b), rho(p) and Hct. Cardiac output and BP were measured to calculate total peripheral resistance. RESULTS: Hct, rho(b), and rho(p) decreased rapidly in the first 20-25 min of immersion and were maintained at a reduced level during immersion. Plasma volume calculated from rho(p) and Hct increased with the rho(b) reduction. These immersion-induced changes were independent of these water temperatures. Plasma osmolality and rho(e) remained constant throughout the experimental period in the three temperature conditions, indicating that the increase in plasma volume and hence hemodilution was induced by an isotonic fluid shift from extravascular space. The total peripheral resistance increased inversely in proportion to the water temperature during HOI. CONCLUSION: In the present condition, water temperature did not modify the net transcapillary fluid transfer during HOI in the presence of the temperature dependent increase in vascular tone.

Adult↗

Orthostatic tolerance and hormonal changes in women during 120 days of head-down bed rest.

BACKGROUND: Women will be included as mission specialists in the upcoming International Space Station program. This paper describes the changes in volume-regulating hormones and determines the degree of degradation in orthostatic tolerance in a group of women after 120 d of bed rest. The aim of this study was to test a countermeasure program to be used by women during long-duration spaceflights. METHODS: For 120 d of -6 degrees head-down bed rest (HDBR), eight healthy women were assigned either to a no-countermeasure (No-CM, n = 4), or to a countermeasure (CM, n = 4) group. In the countermeasure group, exercise began after 2 wk, pharmacological agents were given during the 1st and 3rd mo, and the "Centaur" suit was worn on the last day of bed rest and during the day time for several days after bed rest. Diet supplements were taken during the 1st and 4th mo of HDBR. Tilt tests were run before and after HDBR. RESULTS: After the HDBR, none of the CM subjects, had pre-syncopal or syncopal symptoms during tilt tests: BP was well maintained in the CM group, while heart rate and BP changed in the No-CM group. In plasma, atrial natriuretic peptide (ANP) increased in both groups and remained high throughout HDBR, while aldosterone increased and remained elevated in the No-CM group. Natriuresis was decreased during HDBR. CONCLUSION: The CM protocols used during this study were efficient and prevented orthostatic intolerance for the four CM subjects. It would be necessary to obtain more data regarding this set of CM protocols on female subjects to lead to statistical and formal conclusions.

Adult↗

Increases in body mass of rats during spaceflight: models and measurements.

To test the hypothesis that the body mass of rats is increased during spaceflight, we developed two models from the literature and obtained mass measurements during spaceflight. From studies of centrifugation (hypergravity), there is a reduction in body mass of rats dependent on the exposure gravity level. From data in 18 publications on rats subjected to hypergravity by centrifugation, we developed a model that predicted a 27% increase in body mass during the microgravity of spaceflight. Following spaceflight, with an increase in gravity on return to Earth, there is a reduction in body mass of rats for over 3 d. We related the reduction in body mass after spaceflight to the time after landing that mass measurements were made. From data in 23 publications on rats returning from spaceflight, we developed a model that predicted a 19% increase in body mass during spaceflight. Measurement of body mass of rats on days 6 and 10 of spaceflight found a 7 and 9% increase compared with ground control animals. The increase in body mass during spaceflight suggests that the rat may provide a viable model for metabolic studies in which changes during spaceflight may be predicted in part by ground-based hypergravity studies.

Analysis of Variance↗

[Some mechanisms of modeling the hydrostatic component of hemodynamics in microgravity].

Proposed is a modified method to counteract the headword redistribution of local blood volumes in microgravity by discrete or combined exposure to respiration at negative pressure (RNP) and lower body negative pressure (LBNP). Physically and physiologically substantiated levels of the barometric influences on the central and peripheral hemodynamics to approximate the normal gradients of blood hydrostatic pressure along the body axis are given. Discrete RNP applied to test-subjects during HDT was shown to return the cerebral and cervical hemodynamic parameters to levels determined in horizontal position. Combination of RNP and LBNP had additive character as it advantaged the recovery of values characteristic of the orthostatic position. There are technical possibilities to integrate the LBNP and RNP devices for the benefit of scientific, certification, predictive, and training objectives of space biomedicine.

Adaptation, Physiological↗

[Effect of the body antiorthostatic posture on various circulation and respiration parameters in anesthetised cats].

In anaesthetised cats, antiorthostatic posture of the body with an inclination angle of 30 degrees increased pressure in the vena cava superior and in jugular vein. The rest of the cardio-respiratory parameters were changed insignificantly. Physical and physiological mechanisms of the blood regional redistribution in alteration of the body gravitation orientation, are discussed.

Anesthesia↗

Parasympathetic activity during parabolic flight, effect of LBNP during microgravity.

BACKGROUND/HYPOTHESIS: During parabolic flight, in the standing position, changes are partly due to an acute shift in fluid between the lower extremities, the head and the thorax (Vaïda P, et al. J Appl Physiol 1997; 82:1091-7; and Bailliart O, et al. J Appl Physiol 1998; 85:2100-5). We hypothesized that modifications of parasympathetic activity associated with changes in hydrostatic pressure gradients induced by changes in gravity could be detected by analysis of short time periods. METHODS: We assessed heart rate variability (HRV) in 11 healthy volunteers by indices of temporal analysis (NN, SDNN, RMSSD) and normalized indices such as coefficients of variation CV-SDNN and CV-RMSSD and ratio SDNN/RMSSD. A lower body negative pressure (LBNP) at -50 mm Hg was randomly applied during the microgravity phase (0 Gz) to counteract the lack of hydrostatic pressure in the lower part of the body. RESULTS: NN, CV-SDNN and CV-RMSSD decreased during hypergravity phases and increased during microgravity and during early normogravity (1 Gz) period at the end of parabolas. With LBNP changes are less pronounced at 0 Gz and in the 1 Gz post parabolic period. CONCLUSION: We concluded that parasympathetic nervous activity is recordable by temporal analysis of HRV during short periods of time. LBNP applied during 0 Gz phase reduced the parasympathetic activation at 0 Gz and post parabolic 1 Gz.

Adult↗

Increased and decreased expression of CD69 and CD23, respectively, in gravity-stressed lymphocytes.

BACKGROUND: Recent studies have shown that gravity-changing stress modulates expression levels of cell surface molecules on human lymphocytes. However, previous in vitro microgravity studies have been performed with lymphocytes treated with mitogenic agents. HYPOTHESIS: The aim of the study was to test if exposure of cells to gravity-changing stress alone alters the expression levels of cell surface molecules. Specifically, we examined whether the expression of activation markers is altered after exposure of lymphocytes to combinations of microgravity and hypergravity. METHODS: We used free-fall in parabolic flight for human subjects and a drop-shaft to expose peripheral blood mononuclear cells (PBMC) to gravity-changing stress. After such exposure, PBMC were isolated, and expression levels of CD69, CD23 and CD38 were estimated using three-color flow cytometry. RESULTS: Increased percentages of CD69-positive cells were observed with PBMC from 3 of 4 volunteers who undertook 10 parabolic flights. Exposure of blood to gravity-changing stress in the drop-shaft increased both ratios of CD69-positive cells and levels of CD69 expression on T and B cells. In contrast, the percentages of CD23-positive B cells was decreased. However, gravity-changing stress was not always followed by significant alteration in CD38 expression. CONCLUSIONS: Our findings suggest that CD69 and CD23 might be useful markers that are up- and down-regulated, respectively, after exposure of lymphocytes to gravity-changing stress.

ADP-ribosyl Cyclase↗

Space flight and humoral and cellular immunity of animals.

The use of animal surrogates for the study of the effects of space flight on immune responses is desirable for several reasons. First, animal models are very useful in conditions where the use of human subjects would be difficult. This is certainly true in the space flight environment, where the number of human subjects is small, the human subjects are often too occupied with space flight duties to serve as subjects, and where sampling could be difficult under adverse conditions. Second, because of the intense interest in the immune system, many animal models and reagents already exist that are readily adaptable to space flight studies. Therefore, animal models have been used for many years for space flight studies on immunity. The predominant model used has been the rat, although recently, development of a rhesus monkey model has begun. The focus of this paper will be a description of the results of ground-based and space flight animal models to determine the effects of space flight on immune responses.

Animals↗

Some qualitative and quantitative aspects of the fast-rotating clinostat as a research tool.

In 1958 the geneticist H.J. Muller proposed an extension of the principle of the (slow) plant clinostat which --to a certain extent--abolishes g effects on plant growth (geotropism). Muller predicted that a feeling of weightlessness would be experienced by a human being attached to a clinostat platform, the rotation speed of which is enhanced compared to that of the plant clinostat. This method (called fast-rotating or fast clinostat) was developed by the author in the mid 1960s to investigate the effects of weightlessness on small living objects. This chapter describes the method qualitatively on the basis of a macroscopic functional model and of empirical results obtained using a fast-rotating clinostat microscope. Some practical hints in using the slow and fast clinostat principles are given.

Animals↗

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↗

How well does the clinostat mimic the effect of microgravity on plant cells and organs?

The effect of clinostatting and microgravity on plant cells and organs is considered on the basis of distinguishing two types of gravistimulation: static and dynamic. The former is switched off both by clinostatting and microgravity, the latter is switched off by microgravity but occurs inevitably during clinostatting and may be perceived by cells if the rotation is not fast enough. Effects of clinostatting and microgravity on different examples of static gravistimulation (tonic effects, formation of compression wood, growth of "grass nodes," compensation of epinasty, stabilization of cellular polarity) are considered. The mechanism of the dynamic stimulation is presented; it is related to the displacement of the gravity sensing masses in the cell containing them, and involves disturbance of cytoskeletal tension. The low threshold for gravity perception and short minimal time of dynamic stimulation are emphasized. Only a relatively fast rotating clinostat, on which the radial distance of the cells from the rotational axis is small enough to keep the centrifugal force low, can effectively compensate gravity. However, one must take into account the extreme sensitivity of plants to mechanical stresses that may appear during clinostatting at different levels of plant organization.

Cytoskeleton↗