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Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration.

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.

Acclimatization↗

Selected contribution: redistribution of pulmonary perfusion during weightlessness and increased gravity.

To compare the relative contributions of gravity and vascular structure to the distribution of pulmonary blood flow, we flew with pigs on the National Aeronautics and Space Administration KC-135 aircraft. A series of parabolas created alternating weightlessness and 1.8-G conditions. Fluorescent microspheres of varying colors were injected into the pulmonary circulation to mark regional blood flow during different postural and gravitational conditions. The lungs were subsequently removed, air dried, and sectioned into approximately 2 cm(3) pieces. Flow to each piece was determined for the different conditions. Perfusion heterogeneity did not change significantly during weightlessness compared with normal and increased gravitational forces. Regional blood flow to each lung piece changed little despite alterations in posture and gravitational forces. With the use of multiple stepwise linear regression, the contributions of gravity and vascular structure to regional perfusion were separated. We conclude that both gravity and the geometry of the pulmonary vascular tree influence regional pulmonary blood flow. However, the structure of the vascular tree is the primary determinant of regional perfusion in these animals.

Animals↗

Effects of 2-G exposure on temperature regulation, circadian rhythms, and adiposity in UCP2/3 transgenic mice.

Altered ambient force environments affect energy expenditure via changes in thermoregulation, metabolism, and body composition. Uncoupling proteins (UCPs) have been implicated as potential enhancers of energy expenditure and may participate in some of the adaptations to a hyperdynamic environment. To test this hypothesis, this study examined the homeostatic and circadian profiles of body temperature (T(b)) and activity and adiposity in wild-type and UCP2/3 transgenic mice exposed to 1 and 2 G. There were no significant differences between the groups in the means, amplitudes, or phases of T(b) and activity rhythms at either the 1- or 2-G level. Percent body fat was significantly lower in transgenic (5.2 +/- 0. 2%) relative to the wild-type mice (6.2 +/- 0.1%) after 2-G exposure; mass-adjusted mesenteric and epididymal fat pads in transgenic mice were also significantly lower (P < 0.05). The data suggest that 1) the actions of two UCPs (UCP2 and UCP3) do not contribute to an altered energy balance at 2 G, although 2) UCP2 and UCP3 do contribute to the utilization of lipids as a fuel substrate at 2 G.

Adipose Tissue↗

Male and female rats express similar blood pressure responses to "push-pull" gravitational stress.

Brief exposure to -G(z) ("push") reduces eye-level blood pressure (elbp) during subsequent exposure to +G(z) ("pull"). This is called the "push-pull effect." To evaluate the influence of gender and the axis of rotation (pitch vs. roll) on the push-pull effect, 10 isoflurane-anesthetized male and 10 female Sprague-Dawley rats were restrained supine on a heated tilt board. Rats were subjected to two G profiles: a control profile consisting of rotation from 0 G(z) to 90 degrees head-up tilt (+1 G(z)) for 10 s and a push-pull profile consisting of rotation from 0 G(z) to 90 degrees head-down tilt (-1 G(z)) for 2 s immediately preceding 10 s of +1 G(z) stress. A total of 16 tilts consisting of equal numbers of control and push-pull trials and equal numbers of pitch and roll rotations were imposed by using a counterbalanced design. Gender exerted a significant effect on baseline (0 G(z)) ELBP (pressure was approximately 4 mmHg higher in females). In males and females, ELBP rose to a similar extent ( approximately 8 mmHg) during push, fell to a similar extent (approximately 18 mmHg) during control +G(z) stress, and fell to a similar extent (approximately 22 mmHg) during push-pull +G(z) stress. Altering the axis of rotation between the x-axis (roll) and the y-axis (pitch) did not influence the results. Thus males and females exhibit a push-pull effect; however, gender and axis of rotation do not appear to influence the push-pull effect in anesthetized rats subjected to tilting.

Adrenergic alpha-Agonists↗

Effect of changing the gravity vector on respiratory output and control.

We studied the respiratory output in five subjects exposed to parabolic flights [gravity vector 1, 1.8 and 0 gravity vector in the craniocaudal direction (Gz)] and when switching from sitting to supine (legs bent at the knees). Despite differences in total respiratory compliance (highest at 0 Gz and in supine and minimum at 1.8 Gz), no significant changes in elastic inspiratory work were observed in the various conditions, except when comparing 1.8 Gz with 1 Gz (subjects were in the seated position in all circumstances), although the elastic work had an inverse relationship with total respiratory compliance that was highest at 0 Gz and in supine posture and minimum at 1.8 Gz. Relative to 1 Gz, lung resistance (airways plus lung tissue) increased significantly by 52% in the supine but slightly decreased at 0 Gz. We calculated, for each condition, the tidal volume changes based on the energy available in the preceding phase and concluded that an increase in inspiratory muscle output occurs when respiratory load increases (e.g., going from 0 to 1.8 Gz), whereas a decrease occurs in the opposite case (e.g., from 1.8 to 0 Gz). Despite these immediate changes, ventilation increased, going to 1.8 and 0 Gz (up to approximately 23%), reflecting an increase in mean inspiratory flow rate, tidal volume, and respiratory frequency, while ventilation decreased (approximately -14%), shifting to supine posture (transition time approximately 15 s). These data suggest a remarkable feature in the mechanical arrangement of the respiratory system such that it can maintain the ventilatory output with small changes in inspiratory muscle work in face of considerable changes in configuration and mechanical properties.

Acceleration↗

Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity.

This study was designed to compare the effectiveness of daily short-duration -Gx gravity exposure in preventing adverse changes in skeletal and cardiac muscles and bone due to simulated microgravity. Tail suspension for 28 days was used to simulate microgravity-induced deconditioning effects. Daily standing (STD) at 1 G for 1, 2, or 4 h/day or centrifugation (CEN) at 1.5 or 2.6 G for 1 h/day was used to provide -Gx gravitation as a countermeasure. The results indicate that the minimum gravity exposure requirements vary greatly in different systems. Cardiac muscle is most responsive to such treatment: 1 h/day of -Gx gravitation by STD was sufficient to prevent adverse changes in myocardial contractility; bone is most resistant: 4 h/day of -Gx gravitation only partially alleviated the adverse changes in physical and mechanical properties of the femur. The responsiveness of skeletal muscle is moderate: 4 h/day of -Gx gravitation prevented mass reduction and histomorphometric changes in the soleus muscle during a 28-day simulation period. Increasing gravitational intensity to 2.6 G showed less benefit or no additional benefit in preventing adverse changes in muscle and bone. The present work suggests that system specificity in responsiveness to intermittent gravity exposure should be considered one of the prerequisites in proposing intermittent artificial gravity as a potential countermeasure.

Adrenal Glands↗

Augmentation of the push-pull effect by terminal aortic occlusion during head-down tilt.

Tolerance to positive vertical acceleration (Gz) gravitational stress is reduced when positive Gz stress is preceded by exposure to hypogravity, which is called the "push-pull effect." The purpose of this study was to test the hypothesis that baroreceptor reflexes contribute to the push-pull effect by augmenting the magnitude of simulated hypogravity and thereby augmenting the stimulus to the baroreceptors. We used eye-level blood pressure as a measure of the effectiveness of the blood pressure regulatory systems. The approach was to augment the magnitude of the carotid hypertension (and the hindbody hypotension) when hypogravity was simulated by head-down tilt by mechanically occluding the terminal aorta and the inferior vena cava. Sixteen anesthetized Sprague-Dawley rats were instrumented with a carotid artery catheter and a pneumatic vascular occluder cuff surrounding the terminal aorta and inferior vena cava. Animals were restrained and subjected to a control gravitational (G) profile that consisted of rotation from 0 Gz to 90 degrees head-up tilt (+1 Gz) for 10 s and a push-pull G profile consisting of rotation from 0 Gz to 90 degrees head-down tilt (-1 Gz) for 2 s immediately preceding 10 s of +1 Gz stress. An augmented push-pull G profile consisted of terminal aortic vascular occlusion during 2 s of head-down tilt followed by 10 s of +1 Gz stress. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -20 +/- 1.3, -23 +/- 0.7, and -28 +/- 1.6 mmHg for the control, push-pull, and augmented push-pull conditions, respectively, with all three pairwise comparisons achieving statistically significant differences (P < 0.01). Thus augmentation of negative Gz stress with vascular occlusion increased the magnitude of the push-pull effect in anesthetized rats subjected to tilting.

Acceleration↗

Macromolecular crystallization in microgravity generated by a superconducting magnet.

About 30% of the protein crystals grown in space yield better X-ray diffraction data than the best crystals grown on the earth. The microgravity environments provided by the application of an upward magnetic force constitute excellent candidates for simulating the microgravity conditions in space. Here, we describe a method to control effective gravity and formation of protein crystals in various levels of effective gravity. Since 2002, the stable and long-time durable microgravity generated by a convenient type of superconducting magnet has been available for protein crystal growth. For the first time, protein crystals, orthorhombic lysozyme, were grown at microgravity on the earth, and it was proved that this microgravity improved the crystal quality effectively and reproducibly. The present method always accompanies a strong magnetic field, and the magnetic field itself seems to improve crystal quality. Microgravity is not always effective for improving crystal quality. When we applied this microgravity to the formation of cubic porcine insulin and tetragonal lysozyme crystals, we observed no dependence of effective gravity on crystal quality. Thus, this kind of test will be useful for selecting promising proteins prior to the space experiments. Finally, the microgravity generated by the magnet is compared with that in space, considering the cost, the quality of microgravity, experimental convenience, etc., and the future use of this microgravity for macromolecular crystal growth is discussed.

Animals↗

Laboratory outreach: student assessment of flow cytometer fluidics in zero gravity.

Due to the the clinical utility of the flow cytometer, the National Aeronautics and Space Administration (NASA) is interested in the design of a space flight-compatible cytometer for use on long-duration space missions. Because fluid behavior is altered dramatically during space flight, it was deemed necessary to validate the principles of hydrodynamic focusing and laminar flow (cytometer fluidics) in a true microgravity environment. An experiment to validate these properties was conducted by 12 students from Sweetwater High School (Sweetwater, TX) participating in the NASA Reduced Gravity Student Flight Opportunity, Class of 2000. This program allows high school students to gain scientific experience by conducting an experiment on the NASA KC-135 zero gravity laboratory aircraft. The KC-135 creates actual zero-gravity conditions in 30-second intervals by flying a highly inclined parabolic flight path. The experiment was designed by their mentor in the program, the Johnson Space Center's flow cytometrist Brian Crucian, PhD, MT(ASCP). The students performed the experiment, with the mentor, onboard the NASA zero-gravity research aircraft in April 2000.

Aircraft↗

Immune deficits induced by strenuous exertion under adverse environmental conditions: manifestations and countermeasures.

A brief description is given of the various laboratory and clinical manifestations of immune suppression that arise when strenuous exertion must be carried out in the face of a negative energy balance, shifts of circadian rhythm, sleep deprivation, psychological stressors, and exposure to hostile environments (extremes of heat or cold, high or low ambient pressures, and hyper- or hypo-gravity conditions). From the operational viewpoint, immune suppression could impair both physical and mental performance by increasing susceptibility to opportunistic microorganisms. It is also likely to increase susceptibility to sepsis following trauma or extensive burns, and has occasionally predisposed to fatal myocarditis. The effects of such challenges are complex, in part because of interactions between the various stressors. It is thus important to investigate the impact and to devise appropriate countermeasures with the full physical and intellectual resources of a defense environmental research laboratory. Existing knowledge of the topic is reviewed, and suggestions are made for research that may lead to new and more effective countermeasures.

Energy Metabolism↗

Discontinuous pore fluid distribution under microgravity--KC-135 flight investigations.

Designing a reliable plant growth system for crop production in space requires the understanding of pore fluid distribution in porous media under microgravity. The objective of this experimental investigation, which was conducted aboard NASA KC-135 reduced gravity flight, is to study possible particle separation and the distribution of discontinuous wetting fluid in porous media under microgravity. KC-135 aircraft provided gravity conditions of 1, 1.8, and 10(-2) g. Glass beads of a known size distribution were used as porous media; and Hexadecane, a petroleum compound immiscible with and lighter than water, was used as wetting fluid at residual saturation. Nitrogen freezer was used to solidify the discontinuous Hexadecane ganglia in glass beads to preserve the ganglia size changes during different gravity conditions, so that the blob-size distributions (BSDs) could be measured after flight. It was concluded from this study that microgravity has little effect on the size distribution of pore fluid blobs corresponding to residual saturation of wetting fluids in porous media. The blobs showed no noticeable breakup or coalescence during microgravity. However, based on the increase in bulk volume of samples due to particle separation under microgravity, groups of particles, within which pore fluid blobs were encapsulated, appeared to have rearranged themselves under microgravity.

Alkanes↗

[Usefulness of the Centrifuge Accommodation Module for analyzing gravity responses in plant seedlings].

Onboard centrifuges are indispensable tools for clarifying the effects of microgravity on various physiological processes in plant seedlings. Centrifuges are basically attached to the incubators designed for the International Space Station (ISS). However, because of the limitation in size, that loaded to the Cell Biology Experiment Facility (CBEF) is usable only to some small seedlings such as Arabidopsis. The Centrifuge Accommodation Module (CAM) has great advantages in the size and the amounts of plant materials feasible to load, the quality of acceleration produced, and the easiness of operation on it. The CAM is an apparatus that characterizes the ISS most and its construction on schedule is highly expected.

Centrifugation↗

Behavioral reactions of the bat Carollia perspicillata to abrupt changes in gravity.

As part of an ongoing survey of the behavioral responses of vertebrates to abrupt changes in gravity, we report here on the reactions of bats (Carollia perspicillata) exposed to altered gravity during parabolic aircraft flight. In microgravity, mammals typically behave as if they were upside-down and exhibit repetitive righting reflexes, which often lead to long axis rolling. Since bats, however, normally rest upside-down, we hypothesized that they would not roll in microgravity. Only one of three specimens attempted to fly during microgravity. None rolled or performed any righting maneuvers. During periods of microgravity the bats partially extended their forearms but kept their wings folded and parallel to the body. Between parabolas and occasionally during microgravity the bats groomed themselves. Both the extended limbs and autogrooming may be stress responses to the novel stimulus of altered gravity. This is the first behavioral record of Chiroptera in microgravity.

Animals↗

Effects of static load on the weight and protein content in the leg muscles of the mouse: a simulation of prolonged standing in the workplace.

To simulate the effects of prolonged standing in the workplace on the leg muscles, we subjected mice to centrifugation for 6 wk. The absolute wet weight of leg muscles and internal organs of mice were measured after exposure to 3G by centrifugation for 6 wk and at 2 wk after removal of centrifugation. The weight of the soleus muscle (antigravity muscle) significantly increased after 6-wk exposure to centrifugation, but it decreased to its control weight 2 wk after removal of centrifugation. In contrast, the wet weights of the anterior tibial muscle, liver, and kidneys of mice centrifuged for 6 wk were significantly lower than those of the control mice; they had returned to control levels 2 wk after removal of centrifugation. It was therefore suggested that prolonged standing enlarged the leg muscles but its effect did not last for a long period of time after stopping prolonged standing. Western blot analysis of proteins extracted from the soleus muscle showed that vinculin and alpha-actinin in the centrifuged mice increased slightly, but there were no differences in the heat shock protein 70 (HSP70) and desmin levels between the centrifuged mice and control mice. No difference in HSP 70 suggested that muscle damage did not exist after 6 wk centrifugation.

Animal Experimentation↗

Fine structures of utricle of developing chick embryo exposed to 2G gravity.

Utricular otoconia of the chick embryos incubated under continuous 2G load were examined under a scanning electron microscope. Morphological changes were confined to the process of otoconial formation and the otoconial size. Otoconial formation was remarkably delayed in the utricle of 2G centrifuged chick embryo. Giant otoconia, which sometimes amounted to over 100 microM in length, existed along the marginal zone of the utricular otolithic membrane. These results indicate that the 2G state influences the otoconical formation.

Animals↗