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Central and peripheral sympathetic activities in rats during recovery from simulated weightlessness.

Rats were tail suspended, keeping their forelimbs weight bearing for 14 days, and then allowed to recover for a short (6-h) or a long (24-h) period to assess the behavior of the sympathetic nervous system after weightless simulation. Sympathetic activity was determined by measuring norepinephrine (NE) turnover in the brain stem cell groups involved in central blood pressure control and in organs playing a key role in the cardiovascular regulation (heart and kidneys). The NE turnover was greatly reduced in the rostral (-56%; P < 0.001) and caudal (-73%; P < 0.001) A2 nucleus of suspended rats but was unchanged in the A1, A5, and A6 cell groups compared with attached rats. The NE turnover in the cardiac atria (-34%; P < 0.001) and ventricles (-35%; P < 0.001) and kidneys (-31%; P < 0.001) was decreased after suspension. The central and peripheral sympathetic activities returned to normal within 24 h of release from suspension, but there was hyperactivity after 6 h of recovery. This raises the problem of interpreting the results obtained in animals killed a few hours after return from spaceflight.

Animals

Orthostatic tests after a 4-day confinement or simulated weightlessness.

Besides microgravity, inactivity is likely to play a role in the cardiovascular deconditioning after space flights and weightlessness simulations. The aim of the study was to compare the effects of a 4-day head-down bed rest (HDBR) (-6 degrees) and a 4-day confinement (C) on cardiovascular responses to orthostatic stress. Eight male subjects underwent head-up tilt (HUT) (+60 degrees) and lower-body negative pressure (LBNP) (-20, -30, -40 and -50 mmHg) before (D-1) and at the end (R1) of each situation. Blood pressure, heart rate variability (HRV) and spontaneous baroreflex slope (SBS) were determined. The HDBR reduced orthostatic tolerance, as five subjects presented orthostatic hypotension during the HUT at R1, compared with two subjects at D-1. These same two subjects presented orthostatic hypotension after confinement. The main findings, after HDBR, included reductions in RR interval and total spectral power and a decrease in the parasympathetic indicator (PNS) in favour of a decrease in vagal tone; the increase in the sympathetic indicator (SNS) was not significant. After confinement, the RR interval was also significantly reduced and PNS decreased, but not significantly. RR interval and PNS were further reduced during HUT and LBNP, reflecting a withdrawal of parasympathetic activity. SBS was reduced after HDBR (P < 0.05) and confinement (P = 0.05), with a further reduction during HUT and LBNP without difference between D-1 and R1. This experiment showed that a 4-day HDBR leads to impaired baroreflex function and changes in autonomic balance, which may contribute to orthostatic intolerance. Although less significant, similar patterns of changes in the autonomic nervous system were observed after confinement, suggesting an influence of the inactivity in cardiovascular deconditioning.

Adult

Fluid shifts in vascular and extravascular spaces during and after simulated weightlessness.

To simulate weightlessness in a normal-gravity environment, eight male subjects were tilted 5 degrees head-down for 8 h to determine vascular and extravascular shifts of fluid. Most of the initial loss of leg volume during head-down tilt represented a passive shift of venous blood toward the head. Facial edema, headache, nasal congestion, and a pronounced diuresis were associated with this redistribution of blood volume. As measured by the wick-catheter technique during head-down tilt, interstitial fluid pressure in lower-leg muscle and overlying subcutaneous tissues decreased by 7.4 and 4.4 mmHg, respectively. Interstitial fluid was shifted from the lower legs at a rate of 12 ml X h-1. Dehydration of lower-leg tissues probably resulted from decreased capillary blood pressure within these tissues during tilt. Other transcapillary pressures were unchanged. The abrupt alterations in local blood pressure upon changes in body posture were probably sufficient to explain all shifts of vascular and extravascular fluid. In this regard, countermeasures may be necessary to maintain precapillary-muscle tone during long space flights in order to prevent swelling of lower-leg tissues upon readjustment to Earth's gravity.

Airway Obstruction

Simulated weightlessness: effects of bioenergetic balance.

As a prelude to a flight experiment, an attempt was made to separate energy requirements associated with gravity from all other metabolic needs. The biological effects of weightlessness were simulated by suspending animals in a harness so that antigravity muscles were not supporting the body. Twelve pairs of rats were allowed to adapt to wearing a harness for 5 d. Experimental animals were then suspended in harness for 7 d followed by recovery for 7 d. Control animals were harnessed but never suspended. VO2, VCO2 and rate of 14CO2 expiration from radio-labeled glucose were monitored on selected days. Food intake and body mass were recorded daily. Metabolic rate decreased in experimental animals during 7 d of suspension and returned to normal during recovery. Although some of the metabolic changes may have related to variation in food intake, simulated weightlessness appears to directly affect bioenergetic balance.

Animals

[Energy-metabolism enzymes during combined exposure of the body to simulated weightlessness and gravitational overloads].

Exposure to simulated weightlessness (7-day water immersion and 7-day head-down tilt) caused a decrease in the activity of malate (MDH) and isocitrate dehydrogenase (ICDH), and creatine phosphokinase dehydrogenase (ICDH), and creatine phosphokinase (CPK) at the expense of its MM isoform whereas the activity of alanine (ALT) and aspartate aminotransferase (AST) and pattern of distribution of MDH isoforms remained unchanged. Exposure to acceleration of +3 Gz before and after simulated weightlessness revealed similar changes in the activity of MDH, ICDH, ALT, AST and MDH cytoplasmic fractions. However, the higher increase in the enzyme activity after simulated weightlessness may give evidence for a greater change in cell membrane permeability during acceleration effects that followed simulated weightlessness.

Bed Rest

Sympathetic nervous adjustments in man to simulated weightlessness induced by water immersion.

To clarify the role of the sympathetic nervous system to adjust the fluid shift under weightlessness, muscle and skin sympathetic activities were recorded microneurographically in human subjects under simulated weightlessness induced by water immersion up to the levels of the knee, the navel, the breast and the neck. The muscle and skin sympathetic activities were reduced in proportion to rise of immersion level up to the neck. These changes of sympathetic activities were almost concomitant with those of simultaneously recorded soleus electromyograms and heart rate. Reductions of the thigh and the leg circumference were also confirmed by strain gauge plethysmogram recorded under the same experimental condition. Based on these findings, it is concluded that the sympathetic nervous system is suppressed under weightlessness simulated by water immersion. This suppression might depend mainly on the activation of intrathoracic low pressure receptors, due to the fluid shift toward the upper part of the body. The suppression of the sympathetic nervous system seems to be important to compensate the fluid shift under weightlessness.

Adult

An optimized index of human cardiovascular adaptation to simulated weightlessness.

Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.

Adaptation, Physiological

Plasma viscosity elevations with simulated weightlessness.

Bed rest studies which simulate weightlessness have demonstrated marked changes in the state of hydration of subjects as well as decrements in aerobic capacity. These two phenomena may be linked through increases in blood viscosity which is altered by a loss of free water and which, in turn, influences blood flow needed for aerobic muscular work. This study examines changes in the rheologic properties of blood which attend changes in plasma volume with bed rest in humans and correlates these changes with alterations in aerobic capacity. Eight healthy human subjects were studied on the 6th day of bed rest during two consecutive 10-d bed rest periods separated by a 14-d recovery interval designed to simulate the flight-layover schedule of shuttle astronauts. Plasma viscosity was measured with a Wells-Brookfield viscometer, plasma volume by dye dilution, and maximal aerobic capacity (VO2max) by recumbent cycle ergometry. Bed rest resulted in significant increases in hematocrit and in total plasma protein concentration and fibrinogen concentration, both of which contribute to an elevation in plasma viscosity. The greater than 20% increase in fibrinogen concentration was much greater than could be explained by hemoconcentration. VO2max decreased significantly in the first but not the second bed rest cycle. In many individuals, a decrease in plasma volume and aerobic capacity was coupled with elevated plasma viscosity and hematocrit; however, significant correlations between these variables were lacking. Although significant rheologic perturbations do occur with bed rest, in this study, blood viscosity elevation failed to directly correlate with the reduction in VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Fluid shifts and muscle function in humans during acute simulated weightlessness.

Head-down tilt is considered an effective experimental model to simulate weightlessness. To determine the acute effects of simulated weightlessness on transcapillary fluid balance, tissue fluid shifts, muscle function, and triceps surae reflex time, eight supine subjects were tilted 5 degrees head down for 8 h. A cephalic fluid shift from the legs was indicated by facial edema, nasal congestion, increased urine flow, decreased creatinine excretion, reduced calf girth, and decreased lower leg volume. As measured by wick catheters inserted under local anesthesia, interstitial fluid pressure in the tibialis anterior muscle (4.6 +/- 0.6 mmHg) and subcutaneous tissue (0.6 +/- 0.5 mmHg) of the lower leg fell significantly to -2.8 +/- 0.5 and -3.8 +/- 0.4 mmHg, respectively. Other transcapillary pressures (capillary and interstitial fluid colloid osmotic pressures) were relatively unchanged. Needle-biopsy specimens, obtained just before and after tilt, indicated that total water content of soleus muscle was unchanged during 8 h of head-down tilt. After head-down tilt, isometric strength and isokinetic strength of the plantar flexors were unchanged. Triceps surae reflex time associated with plantar flexion movement slowed slightly after the tilt maneuver. Collectively these results demonstrated a dehydration effect of head-down tilt on muscle and subcutaneous tissues of the lower leg that may affect muscle function.

Adult

Skeletal response to simulated weightlessness: a comparison of suspension techniques.

The skeletal response to simulated weightlessness was studied in rats subjected to two different methods of suspension. Skeletal unloading of the hind limbs for a two week period was achieved by use of either a back harness or tail traction. In comparison to pair-fed control rats, back-suspended rats failed to gain weight whereas tail-suspended rats exhibited normal weight gain. Quantitative bone histomorphometry revealed marked skeletal abnormalities in the proximal tibial metaphysis of back-suspended rats. Loss of trabecular bone mass in these animals was due to a combination of depressed longitudinal bone growth, decreased bone formation, and increased bone resorption. In contrast, the proximal tibia of tail-suspended rats was relatively normal by these histologic criteria. However, a significant reduction in trabecular bone volume occurred during 2 weeks of tail suspension, possibly due to a transient inhibition of bone formation during the early stages of skeletal unloading. Lack of weight gain in back-suspended rats may be indicative of a pronounced stress response during which corticosteroids adversely affected the skeleton. Maintenance of normal weight gain by tail-suspended rats provides evidence for the less traumatic nature of this method of suspension. Our findings indicate that tail suspension may be a more appropriate model for evaluating the effects of simulated weightlessness on skeletal homeostasis.

Adipose Tissue

Contractile properties of the human triceps surae muscle during simulated weightlessness.

The effect of a 120-day period of bed rest on the mechanical properties of human triceps surae muscle was studied in a group of male volunteers (n = 6, mean age 38 years). The results shows that the contractile properties of skeletal muscle in response to disuse change considerably. Time to isometric peak tension of the triceps surae muscle increased from 120 (SEM 3.0)ms to 136 (SEM 2.9)ms (P < 0.01), half relaxation time from 92 (SEM 2.1)ms to 100 (SEM 1.6)ms (P < 0.05) and total contraction time from 440 (SEM 9.9)ms to 540 (SEM 18.7)ms (P < 0.001). Isometric twitch force (Ft) decreased by a mean of 36.7% (P < 0.05), maximal voluntary contraction (MVC) and maximal force (Fmax) by a mean of 45.5% and 33.7%, respectively (P < 0.05-0.01). The value Fmax:Ft ratio increased by 3.6% (nonsignificant). The difference between Fmax and MVC, expressed as a percentage of Fmax and referred to as force deficiency, has also been calculated. Force deficit increased by a mean of 60% (P < 0.001) after bed rest. Force-velocity properties of the triceps surae muscle calculated according to an absolute scale of voluntary and electrically evoked contraction development decreased considerably. The calculations of the same properties on a relative scale did not differ substantially from the initial physiological state. The results would suggest that muscle disuse is associated with both atrophy and a reduction in contractility in the development of Fmax and decreased central (motor) drive. The change in the triceps surae muscle contractile velocity properties may indicate changes in the kinetically active state in the muscles.

Adult

Changes in potassium contractures due to simulated weightlessness in rat soleus muscle.

Some contractile properties of soleus muscle (SOL) fibers isolated from tail-suspended (21 days) rats were compared with those determined in the slow-twitch SOL and the fast-twitch extensor digitorum longus muscle (EDL) of control rats. In SOL from suspended rats, the resting membrane potential and the intracellular Na+ activity were typical of fast-twitch muscles. The relationship between the amplitude of K+ contractures and the membrane potential was steeper for control SOL than for control EDL and suspended SOL. The inactivation curve was also shifted to more positive potentials after suspension. In the presence of perchlorate anions, the tension activation curves of control EDL and suspended SOL were similarly shifted to more negative potentials. Thus, in the present study, modifications induced by suspension in SOL, mainly related to changes in the voltage-sensing process involved in the excitation-contraction coupling mechanism, were that the SOL assumed some of the characteristics of fast-twitch muscles.

Animals

Cerebellar afferents to neuroendocrine cells: implications for adaptive responses to simulated weightlessness.

The hypothalamo-neurohypophyseal system as well as the autonomic nervous system is involved in homeostatic responses associated with changes in head position and orthostatic reflex. The responses induced by body tilt on earth are thought to be attributed to changes in inputs from baroreceptors, vestibular organs and proprioreceptors that are normally required for postural control. The information from these organs is sent to the hypothalamus which thereby influences both neuroendocrine and autonomic systems as well as various kinds of emotional behavior. Our findings showing the fastigial input to the hypothalamus suggested that the FN plays a significant role in these homeostatic responses through its connections with the brain stem and the hypothalamus. Figure 4 shows the input-output organization among the hypothalamus, cerebellum and brain stem, described in detail in sections III to V. This hypothesis may help to account for the autonomic and endocrine disorders often observed in weightlessness.

Adaptation, Physiological

[Role of the hypophysis, hormonal growth inducers and physical exercises in the regulation of function of thyrocytes, C-cells and parathyrocytes in rats during simulated weightlessness].

Immunohistochemistry and histomorphometry were employed to assay thyroid and parathyroid glands in hypophysectomized rats following a10-day tail suspension in head-down position and daily injection of either physiological solution or growth hormone or insulin-like growth factor 1 on the background of physical exercise, i.e. ascent up a 1 m high staircase with a load fastened to the tail. Hypophysectomy was found to cause atrophic/sclerotic changes in the thyroid and parathyroid glands, and dramatically suppress the functional activity of thyrocytes, C-cells (calcitonin producers) and parathyrocytes (parathormone producers). Assumingly, the impairing effect of hypophysectomy on C-cells and parathyrocytes is consequent to the reduced production of thyroid hormones and concomitant moderation of metabolism. The suspension by tail added somewhat to the severity of changes in thyroid and parathyroid glands under the effect of hypophysectomy, whereas the injection of growth hormone or insulin-like growth factor 1 slightly stimulated thyrocytes, C-cells, and parathyrocytes activities; however, it failed to offset the hypophysectomy-provoked developments. Although the activities of thyrocytes, C-cells or parathyrocytes were not affected by physical exercise, there was a mild C-cell proliferation.

Animals

Simulated weightlessness to induce chronic hypoactivity of brain norepinephrine for exercise and stress studies.

Although research on the relationship between exercise training and physiological stress reactivity is increasing, we know little about the involvement of brain neurochemistry. Moreover, the few studies that have been performed have concentrated on animals with normally functioning neurochemistry exposed to an acute stressor. Biomedical research is drawing an association between hypoactivation of the physiological stress response and certain medical conditions. As such, there is a need for an animal model that manifests a chronic hypoactivity of the stress system. In this report we describe the results from studies on norepinephrine changes with actual and simulated weightlessness in animals and humans. There is consistent evidence with rats that 14 d of simulated weightlessness produces reduced norepinephrine turnover in selected brainstem nuclei and peripheral tissue mediating the physiological stress response. Little is known about other brain regions, particularly the hypothlamus. These preliminary data suggest that simulated weightlessness is one method by which a chronic hypoactivity of norepinephrine biosynthesis or release might be induced to study exercise training as an intervention.

Adaptation, Physiological

Effect of simulated weightlessness on the response characteristics of human brain.

In order to systematically investigate the effects of simulated weightlessness on the function state of human brain, 15 degrees head-down tilt (HDT) was used to simulate weightlessness, and the response changes of event-related EEG power spectra, medium-frequency synchronous potentials and slow-waves were examined in the present study. It was found that HDT had characteristic effects on the above EEG responses, suggesting that the effects mainly occurred in the brain's regulatory system, therefore, resulting in changes of the brain function state.

Adolescent

The effects of simulated weightlessness on bone biomechanical and biochemical properties in the maturing rat.

Histomorphometric and biomechanical changes in bone resulting from hypogravity (simulated weightlessness) were examined in this study. Using a head-down hindlimb suspension model, three groups of six male rats underwent simulated weightlessness for periods of one, two and three weeks while a fourth recovery group was suspended for two weeks followed by two weeks of normal activity. Biomechanical data were collected during static and dynamic bending and torsion tests on intact femora. Histomorphometric values were determined from midshaft bone cross sections and material properties were obtained using ash and calcium assays. The experimental groups exhibited significantly lower geometric and material properties than the controls, resulting in structural hypotrophy; geometric and material changes contributed equally to the structural changes. Recovery following a return to normal activity was indicated, although full recovery may take longer than the weightlessness period. In the rat, altered maturation and reduced bone strength were the sequelae of weightlessness.

Aging

Simulated weightlessness and bone metabolism: decrease of alkaline phosphatase activity in the femoral diaphysis of rats.

The effect of simulated weightlessness on bone metabolism was investigated in the skeletal unloading for up to 9 days. The skeletal unloading was designed by using the model of hindlimb hang in rats. The food ingestion of rats with the skeletal unloading was not altered in comparison to that of normal rats. Calcium concentration in the serum was not significantly altered by the skeletal unloading for 9 days, while the serum inorganic phosphorus concentration was significantly decreased at 6 and 9 days. Calcium content in the femoral diaphysis was not altered by the skeletal unloading for 9 days. However, the activities of alkaline and acid phosphatases in the femoral diaphysis were markedly decreased by the skeletal unloading. The decrease in bone alkaline phosphatase activity was seen at 2 days with the skeletal unloading. The present results demonstrate that the skeletal unloading with hindlimb hang can induce the disorder of bone metabolism. This model is useful for studying the effects of simulated weightlessness on bone metabolism.

Alkaline Phosphatase