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Height increase, neuromuscular function, and back pain during 6 degrees head-down tilt with traction.

BACKGROUND: Spinal lengthening and back pain are commonly experienced by astronauts exposed to microgravity. METHODS: To develop a ground-based simulation for spinal adaptation to microgravity, we investigated height increase, neuromuscular function and back pain in 6 subjects all of whom underwent two forms of bed rest for 3 d. One form consisted of 6 degrees of head-down tilt (HDT) with balanced traction, while the other was horizontal bed rest (HBR). Subjects had a 2-week recovery period in between the studies. RESULTS: Total body and spinal length increased significantly more and the subjects had significantly more back pain during HDT with balanced traction compared to HBR. The distance between the lower endplate of L4 and upper endplate of S1, as measured by ultrasonography, increased significantly in both treatments to the same degree. Intramuscular pressures in the erector spinae muscles and ankle torque measurements during plantarflexion and dorsiflexion did not change significantly during either treatment. CONCLUSION: Compared to HBR, HDT with balanced traction may be a better method to simulate changes of total body and spinal lengths, as well as back pain seen in microgravity.

Adaptation, Physiological↗

Simulated microgravity increases myogenic tone in rat cerebral arteries.

Adaptation of the cerebral circulation to microgravity was investigated in rat middle cerebral arteries after 20 days of hindlimb unweighting (HU). Myogenic responses were measured in isolated, pressurized arteries from HU and control animals. Maximal passive lumen diameters, obtained in the absence of extracellular Ca2+ plus EDTA, were not significantly different between groups (249 vs. 258 micrometer). In physiological salt solution, arteries from both HU and control animals maintained a constant lumen diameter when subjected to incremental increases in transmural pressure (20-80 mmHg). However, the diameter of arteries from HU animals was significantly smaller than that of arteries from control animals at all pressures; this difference could be eliminated by exposure to the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. After HU treatment, transient distensibility of the artery wall in response to pressure was also significantly decreased, whereas the frequency and amplitude of vasomotion were increased. The latter changes were not affected by NG-nitro-L-arginine methyl ester. Thus simulated microgravity increases cerebral artery myogenic tone through both nitric oxide synthase-dependent and -independent mechanisms.

Animals↗

[Changes of ERK1/2 in femoral arteries of tail-suspended rats and their effects on contractility].

OBJECTIVE: To study changes of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in femoral arteries of tail-suspended rats and their effects on contractility. METHOD: Microgravity was simulated by elevating the hindquarters of Wistar rats to produce hindlimb unweighting (HU). In the absence or presence of prazosin and PD98059 respectively, isometric tension of vessel rings from femoral arteries in response to norepinephrine (NE) was determined by in vitro perfusion technique; Basal total ERK1/2 level and phosphorylated ERK1/2 level stimulated by norepinephrine in the absence or presence of prazosin and PD98059 respectively were detected by Western blotting-enhanced chemically lightening system. RESULT: The maximal contractile response to NE was significantly lower in femoral arterial rings from 14 day-HU rats as compared with those in control rats. PD98059 caused a marked inhibition of NE-induced maximum contractile response in both control and HU femoral arterial rings. Moreover, the effect of inhibition was more significant in control rats than that in HU rats. Prazosin caused a right shift of the concentration-response curves (CRCs) to NE in both control and HU rats, but no difference was found between the two groups for the PA2 of prazosin calculated by Schild analysis, which showed that the sensitivity of alpha1 adrenoceptor was not changed by HU. After 7d-recovery, the difference of contractile response of femoral arterial rings to NE between recovered group and control group was nonsignificant. Data from Western blotting showed that basal total ERK1/2 levels were elevated in femoral arterial rings from 14d-HU rats as compared with those in control rats, but the levels of basal and NE-stimulated phosphorylated ERK1/2 were higher in control as compared with HU rats. After 7d recovery, the basal total ERK1/2 level and phosphorylated ERK1/2 level were not different from control. CONCLUSION: Microgravity simulated by 14d-HU can induce abnormality of MAPK/ERK pathway, which may contribute to declined contractile response of femoral vessel rings to NE.

Animals↗

Hemodynamic effects of microgravity and their ground-based simulations.

Hemodynamic effects of simulated microgravity were investigated, in various experiments, using radioactive isotopes, in which 40 healthy men, aged 35 to 42 years, took part. Blood shifts were evaluated qualitatively and quantitatively. Simulation studies included bedrest, head-down tilt (-5 degrees and -15 degrees), and vertical water immersion, it was found that none of the methods could entirely simulate hemodynamic effects of microgravity. Subjective sensations varied in a wide range. They cannot be used to identify reliably the effects of real and simulated microgravity. Renal fluid excretion in real and simulated microgravity was different in terms of volume and time. The experiments yielded data about the general pattern of circulation with blood displaced to the upper body.

Adult↗

Influence of gravity on cardiac performance.

Results obtained by the investigators in ground-based experiments and in two parabolic flight series of tests aboard the NASA KC-135 aircraft with a hydraulic simulator of the human systemic circulation have confirmed that a simple lack of hydrostatic pressure within an artificial ventricle causes a decrease in stroke volume of 20%-50%. A corresponding drop in stroke volume (SV) and cardiac output (CO) was observed over a range of atrial pressures (AP), representing a rightward shift of the classic CO versus AP cardiac function curve. These results are in agreement with echocardiographic experiments performed on space shuttle flights, where an average decrease in SV of 15% was measured following a three-day period of adaptation to weightlessness. The similarity of behavior of the hydraulic model to the human system suggests that the simple physical effects of the lack of hydrostatic pressure may be an important mechanism for the observed changes in cardiac performance in astronauts during the weightlessness of space flight.

Biomedical Engineering↗

Relief from glucose interference in microcin B17 biosynthesis by growth in a rotating-wall bioreactor.

Glucose interference in production of microcin B17 by Escherichia coli ZK650 was decreased sevenfold by growth in a ground-based rotating-wall bioreactor operated in the simulated microgravity mode as compared with growth in flasks. When cells were grown in the bioreactor in the normal gravity mode, relief from glucose interference was even more dramatic, amounting to a decrease in glucose interference of over 100-fold.

Anti-Bacterial Agents↗

[Change of pulmonary circulation in microgravity and simulated microgravity].

Fluid is transferred cephalad in microgravity and simulated microgravity, and the pulmonary circulation is the first to be affected. Blood and fluid contents in the lungs increase, but unevenly distributed among various zones of the lungs. Blood vessels in the lungs are filled and distend. Capillary changes have been observed in the animal model of simulated microgravity. Studies about the changes of regulative function of pulmonary circulation are relatively rare. Observations of the reactivity of pulmonary vessels may help to understand the mechanisms of the changes in pulmonary circulation during microgravity.

Animals↗

Effects of 17 days of head-down bed rest on hydro-electrolytic regulation in men.

Prolonged periods of head-down bed rest (HDBR) are commonly used to mimic the effects of microgravity. HDBR has been shown to produce, as in space, a cephalad redistribution of circulating blood volume with an increase in central blood volume which induces the early adaptations in blood volume regulating hormones. Changes in atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity and aldosterone have been observed. Many reports describe these endocrine adaptations but few investigations of rhythms are in the literature. We proposed to evaluate the circadian rhythms of the hormones and electrolytes involved in the hydro-electrolytic regulation during a HDBR study which was designed to simulate a 17-day spaceflight (Life and Microgravity Spacelab experiment, LMS, NASA).

Adult↗

[Effect of upright tilt on venous hemodynamics in rat after three-week tail suspension].

The aim of this work was to know if the venous tone measured in vivo in rat was decreased after 3-week tail suspension, a ground-based model to simulate the effects of microgravity. Arterial and venous pressure measurements during upright tilt did not show any cardiovascular deconditioning. A longer period of tail suspension appears to be necessary to induce changes in venous tone.

Animals↗

Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans.

Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.

Acetylcholine↗

The effect of simulated microgravity on hybridoma cells.

The effect of clinostat-simulated microgravity on SP-2/0 and 1D6 hybridoma cells was studied. Clinorotation during 4-5 days at 1.5 rounds per minute decreased dramatically their proliferating capacity: the rotated cells divided less than once while control cells performed 4-5 divisions. They decreased the non-specific adhesion to tissue culture plastic, but increased the number of cell-to-cell contacts. Such phenomenological changes were accompanied with the alterations in pericellular glycosaminoglycans: decreased accumulation of hyaluronic acid and increased accumulation of chondroitin/dermatan-sulfate, as well as with the increase of cytoplasmic Ca2+ concentration. Clinorotation resulted in hybridoma nicotinic receptor desensitization but not down-regulation. In contrast, both the quantity and quality (molecular isoforms, affinity and specificity) of the antibody produced by 1D6 hybridoma cells were not altered by clinorotation. It is concluded that simulated microgravity affected the proliferating and adhesive, but not biosynthetic properties of hybridoma cells.

Animals↗

Adrenergic vascular control.

The gravity-dependency and age-dependency of noradrenergic vasoconstrictor outflow to skeletal muscle (muscle sympathetic nerve activity; MSNA) in humans was analyzed by applying microneurography technique. The basal level of MSNA in the horizontally supine position increased with aging without significant changes in arterial baroreflex sensitivity. MSNA responded to +Gz load by head-up tilt and to simulated microgravity by thermoneutral head-out immersion with increasing and decreasing the activity, respectively. These gravity related responses of MSNA were age-dependent, being reduced by aging. Simultaneously monitored hemodynamic responses to +Gz load and to simulated microgravity were also age-dependent, being reduced by aging. The gravity-dependent and also age-dependent changes in the noradrenergic vasoconstrictor outflow to muscle seem to be related to the mechanisms controlling the gravity-dependent fluid shift in the human body.

Adolescent↗

Amphibian egg cytoplasm response to altered g-forces and gravity orientation.

Elucidation of dorsal/ventral polarity and primary embryonic axis development in amphibian embryos requires an understanding of cytoplasmic rearrangements in fertile eggs at the biophysical, physiological, and biochemical levels. Evidence is presented that amphibian egg cytoplasmic components are compartmentalized. The effects of altered orientation to the gravitational vector (i.e., egg inversion) and alterations in gravity force ranging from hypergravity (centrifugation) to simulated microgravity (i.e., horizontal clinostat rotation) on cytoplasmic compartment rearrangements are reviewed. The behavior of yolk compartments as well as a newly defined (with monoclonal antibody) non-yolk cytoplasmic compartment, in inverted eggs and in eggs rotated on horizontal clinostats at their buoyant density, is discussed.

Animals↗

Effects of simulated microgravity on the development and maturation of dissociated cortical neurons.

Although a wealth of evidence supports the hypothesis that some functions of the nervous system may be altered during exposure to microgravity, the possible changes in basic neuronal physiology are not easy to assess. Indeed, few studies have examined whether microgravity affects the development of neurons in culture. In the present study, a suspension of dissociated cortical cells from rat embryos were exposed to 24 h of simulated microgravity before plating in a normal adherent culture system. Both preexposed and control cells were used after a period of 7-10 d in vitro. The vitality and the level of reactive oxygen species of cultures previously exposed did not differ from those of normal cultures. Cellular characterization by immunostaining with a specific antibody displayed normal neuronal phenotype in control cells, whereas pretreatment in simulated microgravity revealed an increase of glial fibrillary acidic protein fluorescence in the elongated stellate glial cells. Electrophysiological recording indicated that the electrical properties of neurons preexposed were comparable with those of controls. Overall, our results indicate that a short time of simulated microgravity preexposure does not affect dramatically the ability of dissociated neural cells to develop and differentiate in an adherent culture system.

Animals↗

Locomotion in simulated zero gravity: ground reaction forces.

BACKGROUND: Exercise is likely to be an important countermeasure to bone demineralization, which remains a concern for astronauts during long-duration spaceflight. However, loads on the feet during exercise with 1 G equivalent gravity replacement are not known. The purpose of this study was to compare ground reaction forces (GRFs) during over-ground and simulated zero gravity (0 G) locomotion. HYPOTHESIS: It was hypothesized that sufficient gravity replacement loading could be applied to the subjects such that GRF profiles similar to those seen in 1 G would occur during locomotion in a zero-gravity locomotion simulator (ZLS). METHODS: GRFs were measured during overground walking and running, and during locomotion in two restraint harness designs in the ZLS with an initial loading of 1 body weight. Load cells measured the gravity replacement load (GRL) in the ZLS. Joint angles at the hip and knee were also measured by goniometers. RESULTS: Peak forces were greater in overground locomotion than in the ZLS; however, loading rates were greater in the ZLS running conditions than in overground running. The knee joint was more flexed at key times in the support phase during running in the ZLS compared with overground. CONCLUSIONS: Large loads and loading rates can be generated at the feet during simulated 0 G exercise although peak forces during running in the ZLS are less than overground running at the same speed. The refinement of the gravity replacement system to provide a constant 1 G load should be considered.

Adult↗

Enhancing circulation to lower limbs during head-down tilt by warming upper body and thighs.

BACKGROUND: Long-duration spaceflight results in deconditioning of the cardiovascular system, loss of fluid volume, bone demineralization, and atrophy of skeletal muscles, particularly affecting the lower limbs. We hypothesized that it is possible to improve blood circulation to the lower extremities in simulated microgravity by forcing the blood to deliver heat to the feet through heating parts of the upper body and thighs. METHODS: In Study 1, seven men and four women were assessed in an environmental chamber with head-down tilt (HDT) at 14 degrees, wearing a newly developed shortened multi-compartment liquid cooling/warming garment (SLCWG) with local tubing networks covering parts of the head, torso, thigh, arms, and hands, with fingers, lower leg, and feet exposed. Study 2 was the same as Study 1 with a new cohort of four men and two women, and the assessment of toe blood perfusion on all subjects. Heat was applied as follows: Stage 1--SLCWG inlet water temperature 33 degrees C to stabilize comfort; Stage 2--inlet water temperature 8-10 degrees C (in combination with HDT) to reach a criterion of 25 degrees C finger temperature (Tfing); and Stage 3--inlet water temperature 45 degrees C to restore Tfing to 33 degrees C. RESULTS: Improvement of foot circulation by delivering more heat to the upper body and thighs was noted; increases in toe temperature (Ttoe) suggest enhanced perfusion. From Stage 2 to 3, there were significant increases in Ttoe (p < 0.05), a significant decrease in diastolic BP (DBP) (p < 0.05), and a significant change across stages in subjective perception of foot comfort (p < 0.001) and foot heat (p < 0.06). Further, toe blood perfusion increased significantly from Stage 2 to 3 (p < 0.05). CONCLUSIONS: Moderate partial heating of the upper body/thighs improved blood circulation in the feet in simulated microgravity by delivering heat to the lower extremities through restriction of heat exchange with the environment in the heated body parts. This technique could serve as a supplemental countermeasure for increasing blood circulation to the lower extremities.

Adult↗

Dobutamine as a countermeasure for reduced exercise performance of rats exposed to simulated microgravity.

Post-spaceflight results and findings from humans and rodents after conditions of bed rest or simulated microgravity indicate maximum exercise performance is significantly compromised. However, the chronic administration of dobutamine (a synthetic adrenomimetic) to humans in relevant experiments improves exercise performance by mechanisms that prevent the decline in peak O2 consumption (VO2peak) and reduce the concentration of lactic acid measured in the blood. Although dobutamine restores maximum VO2 values in animals participating in simulated microgravity studies, it is unknown whether injections of this alpha 1-, beta 1-, and beta 2-adrenoceptor agonist in rats will enhance exercise performance. To investigate this, adult male rats were assigned to three experimental groups: caged control receiving saline; head-down, tail-suspended (HDS) receiving saline (HDS-S); and an HDS group receiving dobutamine hydrochloride injections (1.8 mg/kg twice daily per rat). Treadmill tests were performed before suspension, at 14 days, and after 21 days. VO2peak, run time, and the rate of rise in colonic temperature (heating index) were evaluated after 14 days, whereas at 21 days, hemodynamic responses (heart rate, systolic blood pressure, and double product) were determined during submaximal exercise with blood pH, blood gases, and lactic acid concentration values obtained during maximal exercise. In contrast to the results for the HDS-S rats, dobutamine administration did restore VO2peak and "normalized" lactic acid concentrations during maximal exercise. However, daily injections were unable to enhance exercise performance aspects associated with treadmill run time, the mechanical efficiency of running, the heating index, or the retention of muscle and body mass. These simulated microgravity findings suggest that dobutamine's potential value as a countermeasure for postflight maximal performance or for egress emergencies is limited and that other countermeasures must be considered.

Adrenergic beta-Agonists↗

Effects of head-down-tilt bed rest on cerebral hemodynamics during orthostatic stress.

Our aim was to determine whether the adaptation to simulated microgravity (microG) impairs regulation of cerebral blood flow (CBF) during orthostatic stress and contributes to orthostatic intolerance. Twelve healthy subjects (aged 24 +/- 5 yr) underwent 2 wk of -6 degrees head-down-tilt (HDT) bed rest to simulate hemodynamic changes that occur when humans are exposed to microG. CBF velocity in the middle cerebral artery (transcranial Doppler), blood pressure, cardiac output (acetylene rebreathing), and forearm blood flow were measured at each level of a ramped protocol of lower body negative pressure (LBNP; -15, -30, and -40 mmHg x 5 min, -50 mmHg x 3 min, then -10 mmHg every 3 min to presyncope) before and after bed rest. Orthostatic tolerance was assessed by using the cumulative stress index (CSI; mmHg x minutes) for the LBNP protocol. After bed rest, each individual's orthostatic tolerance was reduced, with the group CSI decreased by 24% associated with greater decreases in cardiac output and greater increases in systemic vascular resistance at each level of LBNP. Before bed rest, mean CBF velocity decreased by 14, 10, and 45% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. After bed rest, mean velocity decreased by 16% at -30 mmHg and by 21, 35, and 39% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. Compared with pre-bed rest, post-bed-rest mean velocity was less by 11, 10, and 21% at -30, -40, and -50 mmHg, respectively. However, there was no significant difference at maximal LBNP. We conclude that cerebral autoregulation during orthostatic stress is impaired by adaptation to simulated microG as evidenced by an earlier and greater fall in CBF velocity during LBNP. We speculate that impairment of cerebral autoregulation may contribute to the reduced orthostatic tolerance after bed rest.

Adult↗