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Physiological properties of rat hind limb muscles after 15 days of simulated weightless environment.

Weightlessness during space mission results in atrophic changes in those muscles which have maximum weight bearing function and consist primarily of slow twitch fibres. In the present study an animal model was designed to evaluate the effects of 15 days of hindlimb unloading (HU) in rats by tail suspension on the (i) weight of gastrocnemius (G), plantaris (P), both predominantly having fast twitch fibres and soleus (S) muscle, predominantly having fast twitch fibres and (ii) contractile properties viz peak twitch contraction (Pt) and peak tetanic contraction (Po) of GPS muscle. HU rats showed significant weight reductions of G (-17.9%), P (-13.3%) and S (-41.2%) muscles. Pt and Po were also reduced in HU group but when these were expressed per gm of GPS muscle, no significant changes in Pt and Po were observed. These findings confirm that HU in rats result in maximum atrophic change in those muscles which have predominantly slow twitch fibres and reductions in contractile properties of muscles are in proportion to reduction in muscle weight. Also, HU by tail suspension provides a good ground based model for developing the deconditioning of muscles as applicable to weightlessness of space and offers a scope for the development of various countermeasures.

Animals↗

[Changes in the NO-dependent regulation of the local cerebral blood flow in rats during adaptation to the conditions of simulated weightlessness].

The nitrogen oxide NO-dependent regulation of the cerebral blood flow was studied before and after 24-hr head-down immobilization (HDI) of intact and pre-trained rats. Training consisted in 2-hr tail-suspension each day of the 2-wk period. Blood flow was determined with the laser Doppler flowmetry following local injection of a NO synthesis blocker (L-NAME), and NO (sodium nitroprusside). Neither HDI nor pre-training per se influenced NO tonic production in the cortex of large hemispheres and cerebellum. However, in pre-trained animals HDI resulted in a significant blood flow response to the local blockade of NO synthesis in the cerebellum. None of the animals changed the reaction of the blood flow to the local injection of sodium nitroprusside. The conclusion was drawn that alteration in the NO-dependent regulation of the brain blood flow in pre-trained animals could manifest of adaptation to HDI in the course of 24-hr suspension.

Adaptation, Physiological↗

Bone loss during simulated weightlessness: a biomechanical and mineralization study in the rat model.

BACKGROUND: Astronauts exposed to weightlessness for extended periods experience significant decreases in bone mineral density. The clinical implications of this demineralization are not entirely clear, and the biomechanics involved are not completely understood. HYPOTHESIS: Local (rather than global) measurements of geometry and calcium concentration effectively predict femur strength in adult rats exposed to a hind-limb suspension model of weightlessness. METHODS: Female Fischer rats (6-mo-old) were divided into groups of control and hind-limb-suspended animals. Animals were sacrificed after 2 or 4 wk of hind-limb suspension, and both femurs removed from each animal. The 3-point bending strength and total bone mineralization were determined for one femur from each animal, and the mid-shaft cross-sectional geometrical properties and distribution of calcium were determined for the contralateral femur. RESULTS: Although suspension led to significant decreases in total bone mineralization, the concentration of calcium at the anterior periosteal surface was unaffected. Total bone percent mineralization was not well correlated with structural properties, but bone geometrical properties (particularly cross-sectional moment of inertia and length) correlated strongly with ultimate bending strength (r2 = 0.81). Differences in bone geometry due to suspension were consistent with a distribution of bone material closer to the axis of the femur. CONCLUSIONS: Structural properties of bone are predicted well by bone geometry and poorly by total bone percent mineralization. Decreased bone mechanical strength in this model of weightlessness is primarily due to a distribution of bone material nearer the axis of the bone.

Animals↗

[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↗

Contributory factors to orthostatic intolerance after simulated weightlessness.

Various factors may contribute to orthostatic intolerance (OI) observed after space flights or simulated weightlessness such as bed rest experiments: individual physical and physiological factors (arterial blood pressure (BP), height), physiological changes induced by real or simulated weightlessness (hypovolaemia, increase in venous distensibility), and space flight or simulation conditions (duration and counter-measure application). Our purpose was to test which of these factors were dominant in contributing to the OI. This was assessed in 47 healthy men participating in bed rest experiments of 4, 14, 28, 30 and 42 days, with or without counter-measures (medical stockings, lower-body negative pressure (LBNP), LBNP + muscular exercise). Nineteen subjects did not finish the orthostatic test (60 degrees head-up tilt or stand test) after bed rest. The occurrence of OI was associated with greater height, low resting BP, greater changes in resting lower-limb venous distensibility throughout the bed rest, and absence of counter-measures.

Adult↗

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↗

Influences of chemical sympathectomy and simulated weightlessness on male and female rats.

Maximum oxygen consumption (VO2max) has been shown to be reduced after periods of simulated weightlessness. To assess the role of the sympathetic nervous system in these reductions, Sprague-Dawley rats were either chemically sympathectomized (SYMX) or injected with saline (SHAM) and assigned to head-down suspension (HDS), horizontal restraint with the hindlimbs weight bearing (HWB), or cage-control (CC) conditions. VO2max, run time (RT), and mechanical efficiency (ME) were measured before suspension and on days 7 and 14. Male and female SHAM HDS groups exhibited reduced measures of VO2max (12-13%) after 7 and 14 days, and this decrease was attenuated in the SYMX and HWB rats. HDS resulted in a significant reduction in RT (9-15%) in both the male and female rats, and ME was significantly reduced after HDS in male and female SYMX and male SHAM rats (23-33%) but not in the female SHAM rats. Lesser reductions in ME were observed in the HWB rats. HDS and HWB were associated with lower body, fat-free, and fat masses, which were similar in male and female rats as well as for the SHAM and SYMX conditions. In a related HDS experiment with normal rats, plasma norepinephrine and epinephrine were increased by 53 and 42% after 7 days, but only epinephrine returned to baseline after 14 days. It was concluded that chemical sympathectomy and/or a weight-bearing stimulus will attenuate the loss in VO2max associated with simulated weightlessness in rats despite similar changes in body mass and composition. The mechanism(s) remains unclear at this time.

Adrenal Glands↗

Changes in vitamin A status following prolonged immobilization (simulated weightlessness).

A study was conducted to investigate the effects of a simulated weightlessness induced by chronic immobilization on vitamin A status. To simulate the stress condition of weightlessness, rats were suspended for 10 days in a special jacket to which metal chains were attached. Animals received a commercial stock diet. Control rats were pair-fed in reference to the suspended rats. As compared with the control, prolonged immobilization resulted in a decrease in body weight gain and an increase in adrenal weight occurred. In the suspended rats, serum concentrations of retinol and retinol-binding protein (RBP) declined. Hepatic retinyl palmitate content increased, and the hepatic retinol level was decreased. The prolonged immobilization led to significantly reduced retinyl palmitate levels in the testis and lung as well as lowered testicular retinol levels. The results suggest that the stress state induced by prolonged immobilization caused accumulation of hepatic retinyl palmitate, decreasing the serum retinol concentration and retinyl ester content in the extrahepatic tissues.

Adrenal Glands↗

[Interrelationship between pulse filling of earlobe vessels and cardiac extrasystole during "head--foot" loading following exposure to simulated weightlessness].

The relationship between changes in the pulse blood filling of earlobe vessels and cardiac arrhythmias was studied in 91 manned experiments during which test subjects were exposed to simulated weightlessness and then to acceleration of +3 Gz for 5 min in a 7.25 m arm centrifuge. The studies demonstrated that the vascular type of functional decompensation may transform into the cardiac type in normal men during recovery from an exposure to +3 Gz and simulated weightlessness. This may be of theoretical and practical importance for space programs.

Adult↗

Brain norepinephrine changes with simulated weightlessness and relation to exercise training.

Maintenance of nervous system function during periods of a deconditioning syndrome is important to prevent diminished psychological/behavioral, and physiological function observed during periods of bed rest, physical inactivity, and weightlessness. A main neurotransmitter is norepinephrine (NE), and its regulation yields insight into nervous system function. This research tested the hypotheses that, 1) deconditioning syndrome induced by simulated weightlessness of 9 days via the head-down tilt (HDT) model results in a blunted noradrenergic turnover rate in selected brain tissue and, 2) that exercise training acts as a countermeasure for these changes in noradrenergic activity. Male Sprague-Dawley rats (3 months, n = 60) were divided into either a HDT (HDT, n = 20), cage control (CAGE-CN, n = 20) or an exercise trained HDT (HDT-EX, n = 20) group. Each group was further subdivided into a saline (n = 10) or alpha-methyl-tyrosine (AM, n = 10) (200 mg/kg) injected subgroup. Animals in the HDT groups were tail suspended in a 30 degrees head-down tilt position for 9 days. Norepinephrine turnover was determined 3 h following administration of saline or alpha-methyl-para-tyrosine. The NE turnover rate (ng gm(-1) x h(-1)) for the CN, HDT, and HDT-EX groups, respectively, were as follows: locus coeruleus, 63 +/- 33, *134 +/- 65, 85 +/- 61; hypothalamus, 195 +/- 50, *47 +/- 47; *93 +/- 34; cerebellum, 10 +/- 18, *65 +/- 15, *53 +/- 19; cerebral cortex, 6 +/- 20, *28 +/- 15, *68 +/- 22. (*Denotes significant difference from the control group at the p < or = 0.05 level of significance; +denotes significant difference from the HDT group at the p < or = 0.05 level of significance.) These findings suggest that: 1) norepinephrine turnover rate adapts in a tissue-specific manner following a 9-day tail suspension, 2) increased norepinephrine turnover rates and norepinephrine tissue content in the HDT group are consistent with neural adaptation to a chronic stress response.

Analysis of Variance↗

Effect of a simulated weightlessness model on the production of rat interferon.

A rat model simulating some aspects of weightlessness was used to determine whether simulated weightlessness might alter interferon production. The optimum time for in-vivo induction of alpha/beta interferon (alpha/beta-IFN) by polyriboinosinic-polyribocytidylic acid was determined to be four hours in normal, mature rats. Rats suspended in the model for two weeks were injected with polyriboinosinic-polyribocytidylic acid and bled four hours later. A dramatic decrease (80%) in alpha/beta-IFN production was observed in those animals exposed to simulated weightlessness as compared to control rats. These data suggest that weightlessness may alter certain immunological functions.

Animals↗

Logistic risk model for the unique effects of inherent aerobic capacity on +Gz tolerance before and after simulated weightlessness.

Small sample size (n less than 10) and inappropriate analysis of multivariate data have hindered previous attempts to describe which physiologic and demographic variables are most important in determining how long humans can tolerate acceleration. Data from previous centrifuge studies conducted at NASA/Ames Research Center, utilizing a 7-14 d bed rest protocol to simulate weightlessness, were included in the current investigation. After review, data on 25 women and 22 men were available for analysis. Study variables included gender, age, weight, height, percent body fat, resting heart rate, mean arterial pressure, VO2max, and plasma volume. Since the dependent variable was time to greyout (failure), two contemporary biostatistical modeling procedures (proportional hazard and logistic discriminant function) were used to estimate risk, given a particular subject's profile. After adjusting for pre-bed-rest tolerance time, none of the profile variables remained in the risk equation for post-bed-rest tolerance greyout. However, prior to bed rest, risk of greyout could be predicted with 91% accuracy. All of the profile variables except weight, MAP, and those related to inherent aerobic capacity (VO2max, percent body fat, resting heart rate) entered the risk equation for pre-bed-rest greyout. A cross-validation using 24 new subjects indicated a very stable model for risk prediction, accurate within 5% of the original equation. The result for the inherent fitness variables is significant in that a consensus as to whether an increased aerobic capacity is beneficial or detrimental has not been satisfactorily established. We conclude that tolerance to +Gz acceleration before and after simulated weightlessness is independent of inherent aerobic fitness.

Acceleration↗

Osteoblast histogenesis in periodontal ligament and tibial metaphysis during simulated weightlessness.

According to nuclear size, fibroblast-like cells adjacent to bone surfaces in the periodontal ligament (PDL) and tibial primary spongiosa (PS) were classified as less differentiated progenitors and committed osteoprogenitors (A/A'), nonosteogenic cells (B), or preosteoblasts (C/D). The ratio of A/A' to C/D cells reflects osteogenic status of bone lining tissue. When 83-day-old rats were subjected to simulated weightlessness (S-W) for 17 d and examined for changes in osteoblast histogenesis, PDL and PS cell populations increased in A/A' cells (p less than 0.01; less than 0.05) but decreased in C/D cells (p less than 0.01; less than 0.05) compared to controls. These data indicate that the nuclear volume method, originally developed in PDL, can also be used to assess osteoblast histogenesis in PS of long bones, and that simulated weightlessness in the present experimental context interferes with osteoblast histogenesis. Since the surfaces of both weightbearing (PS) and nonweightbearing (PDL) bones were affected, systemic factors appear important in the gravity-related mechanism of osteoblast histogenesis. Although unloading of the tibia and cephalad fluid shifts occur during S-W, the data attained in this experiment could also be explained by stress and/or cessation of growth in the S-W rats.

Animals↗

Leg vascular responsiveness during acute orthostasis following simulated weightlessness.

Ten men (35-49 years old) underwent lower body negative pressure (LBNP) exposures before and after 10 d of continuous 6 degrees head-down bedrest in order to predict the effect of weightlessness on the responsiveness of leg vasculature to an orthostatic stress. Heart rate (HR), mean arterial blood pressure (MAP), and impedance rheographic indices of arterial pulse volume (APV) of the legs were measured during rest and at 1 min of -30 mm Hg LBNP. Bedrest-induced deconditioning was manifested by decreases (p less than 0.05) in plasma volume (17%), peak oxygen uptake (16%), and LBNP tolerance (17%). Resting HR was unchanged after bedrest, but HR was higher (p less than 0.05) at 1 min of -30 mm Hg LBNP after, compared with before, bedrest. Responses of MAP to -30 mm Hg LBNP were not altered by bedrest. Resting APV was decreased (p less than 0.05) by simulated weightlessness. However, APV was reduced (p less than 0.05) from rest to 1 min -30 mm Hg LBNP by the same relative magnitude before and after bedrest (-21.4 +/- 3.4% and -20.5 +/- 2.7%, respectively). We conclude that peripheral arterial vasoconstriction, as indicated by reductions in APV during LBNP, was not affected by bedrest. These results suggest that there was no apparent alteration in responsiveness of the leg vasculature following simulated weightlessness. Therefore, it appears unlikely that control mechanisms of peripheral resistance contribute significantly to reduced orthostatic tolerance following spaceflight.

Adaptation, Physiological↗

Simulated weightlessness and bone metabolism: gravitational stimulation enhances insulin sensitivity.

The effect of simulated weightlessness on bone metabolism was investigated in skeletal unloading for 4 days. Skeletal unloading was designed using the model of hindlimb hang in rats. Skeletal unloading with hindlimb hang cased a significant decrease of alkaline phosphatase activity, deoxyribonucleic acid (DNA) content, and glucose consumption in the femoral diaphysis, but not in the calvaria. When femoral-diaphyseal tissues were cultured in the presence of insulin (10(-8) M), the hormone produced a significant increase of alkaline phosphatase activity and decrease of glucose consumption in the femoral-diaphyseal tissues obtained from normal rats. This hormonal effect was not seen in the femoral diaphysis, but in the calvaria, of rats with skeletal unloading. However, insulin effect was seen in the femoral diaphysis obtained at 3 days after the removal of skeletal unloading. Meanwhile, the presence of other bone-regulating factors (10(-8) M parathyroid hormone [1-34] and 10(-4) M zinc sulfate) revealed an appreciable effect on alkaline phosphatase activity in the femoral diaphysis from rats with skeletal unloading. These results suggest that gravitational stimulation can directly enhance a specific insulin sensitivity in the regulation of bone metabolism.

5'-Nucleotidase↗