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PubMed1999

Signal transduction in T lymphocytes--a comparison of the data from space, the free fall machine and the random positioning machine.

In this paper we discuss the effect of microgravity on T cells and we present the data of studies with two new machines for 0 g simulations. Several experiments in space show that mitogenic T cell activation is lost at 0 g. Immunocytochemistry indicates that such effect is associated with changes of the cytoskeleton. Biochemical studies suggest that the lack of expression of the interleukin-2 receptor is one of the major causes of the loss of activity. In fact, interleukin-2 is the third signal required for full activation. In order to deepen our investigations we are now working with the free-fall machine, FFM, invented by D. Mesland, and with the random positioning machine, RPM, or three-dimensional clinostat, developed by T. Hoson. The FFM produces periods of free-fall lasting approximately 800 ms followed by bounces of 15-30 g lasting 45-60 ms. The RPM eliminates the effect of gravity by rotating biological specimen randomly around two orthogonal axes. While the FFM failed to reproduce the results obtained with T lymphocytes in space, the data from the RPM are in good agreement with those in real microgravity. In fact, the inhibition of the mitotic index in the RPM is 89% compared to static controls. The RPM (as the FFM) can carry markedly larger specimen than the fast rotating clinostat and thus allows to conduct comprehensive studies to select suitable biological objects for further investigations in space.

Cells, Cultured↗
PubMed2005

Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice.

Whether myocardial contractile impairment contributes to orthostatic intolerance (OI) is controversial. Accordingly, we used transient bilateral carotid occlusion (TBCO) to compare the in vivo pressor, chronotropic, and inotropic responses (parts 1 and 2) to open-loop selective carotid baroreceptor unloading in anesthetized mice. In part 3, in vitro myocyte responses to isoproterenol in mice exposed to hindlimb unweighting (HLU) for approximately 2 wk were determined. Heart rate (HR) and mean arterial pressure (MAP) responses to TBCO were measured. In control mice, TBCO increased HR (15 +/- 2 beats/min, P < 0.05) and MAP (17 +/- 2 mmHg, P < 0.05). These responses were markedly potentiated in denervated control (DC) mice, in which the aortic depressor nerve and sympathetic trunk were sectioned before measurement. Baroreflex responses to TBCO were eliminated by blockade with hexamethonium bromide (10 microg/kg). In HLU (denervated) mice, HR and MAP responses were reduced approximately 70% compared with DC mice. In part 2, myocardial contractile responses to TBCO were measured with a left ventricular micromanometer-conductance catheter. TBCO in DC mice increased the slope of the end-systolic pressure-volume relation (end-systolic elastance) by 86 +/- 13%. This inotropic response was attenuated (14 +/- 10%, P < 0.005) after HLU. In part 3, contractile responses to isoproterenol were impaired in myocytes isolated from HLU mice. In conclusion, selective carotid baroreceptor unloading stimulates HR, blood pressure, and myocardial contractility, and HLU attenuates each response. These findings have important implications for the management of OI in astronauts, the elderly, and individuals subjected to prolonged bed rest.

Animals↗
PubMed2005

The effect of simulated microgravity by three-dimensional clinostat on bone tissue engineering.

Evidence suggests that mechanical stress, including gravity, is associated with osteoblast differentiation and function. To examine effects of microgravity on bone tissue engineering, we used a three-dimensional (3D) clinostat manufactured by Mitsubishi Heavy Industries (Kobe, Japan). A 3D clinostat is a device that generates multidirectional G force. By controlled rotation on two axes, it cancels the cumulative gravity vector at the center of the device. We cultured rat marrow mesenchymal cells (MMCs) in the pores of interconnected porous calcium hydroxyapatite (IP-CHA) for 2 weeks in the presence of dexamethasone using the 3D clinostat (clinostat group). MMCs cultured using the 3D clinostat exhibited a 40% decrease in alkaline phosphatase activity (a marker of osteoblastic differentiation), compared with control static cultures (control group). SEM analysis revealed that although there was no difference between the two groups in number or distribution of cells in the pores, the clinostat group exhibited less extensive extracellular matrix formation than the control group. Cultured IP-CHA/MMC composites were then implanted into subcutaneous sites of syngeneic rats and harvested 8 weeks after implantation. All implants showed bone formation inside the pores, as indicated by decalcified histological sections and microfocus computed tomography. However, the volume of newly formed bone was significantly lower for the clinostat group than for the control group, especially in the superficial pores close to the implant surface. These results indicate that new bone formation in culture was inhibited by use of the 3D clinostat, and that this inhibition was mainly due to suppression of osteoblastic differentiation of MMCs.

Animals↗
PubMed2002

A countermeasure to ameliorate immune dysfunction in in vitro simulated microgravity environment: role of cellularnucleotide nutrition.

Considerable evidence suggests that space travelers are immunosuppressed, presumably by microgravity environmental stresses, putting them at risk for adverse effects, such as opportunistic infections, poor wound healing, and cancer. The purpose of this study was to examine the role and mechanisms of nucleotide (NT) supplementation as a countermeasure to obviate immunosuppression during space travel. The in vitro rotary cell culture system, a bioreactor (BIO), was used to simulate the effect of microgravity and to isolate the neuroendocrine effects inherent to in vitro models. The splenocytes from normal mice were cultured in BIO and control tissue culture (TC) flasks with and without phytohemagglutinin (PHA) for mitogen assays. The culture medium was then supplemented with various concentrations of a nucleosides-nucleotides mixture (NS + NT), inosine, and uridine. Cytokines interleukin (IL)-1beta, IL-2, IL-3, tumor necrosis factor-alpha, and interferon (IFN)-gamma were measured from the supernatant by enzyme-linked immunosorbent assay. In the PHA-stimulated cultures the cellular proliferation in the BIO was significantly decreased as compared with the TC flask cells. BIO-cultured cells in the presence of NS + NT maintained mitogen responses similar to the control TC flask cells. The maintenance of the mitogen response in BIO was observed by the supplementation of uridine and not of inosine. These results are in agreement with our earlier results from unit gravity experiments that showed that pyrimidines are more effective in pleiogenic immunoprotection to hosts. Cytokines IL-1beta, IL-2, and IFN-gamma in the BIO supernatants of cells cultured in the presence of NS + NT had a significantly higher response than the control vessel. Thus, supplemental NT, especially pyrimidines, can confer immune protection and enhance cytokine responses during space travel.

Animals↗
PubMed2005

Intracranial pressure dynamics assessed by noninvasive ultrasound during 30 days of bed rest.

INTRODUCTION: Intracranial pressure (ICP) may be an important contributor to symptoms of space adaptation syndrome during the initial days of microgravity exposure. The temporary nature of these symptoms suggests that some physiologic adaptation or compensation occurs. Fluid shifts similar to those in microgravity can be simulated on Earth using head-down tilt (HDT) bed rest. This study was performed to calibrate a new noninvasive ICP instrument and to investigate ICP adaptation during 30 d of HDT bed rest. METHODS: A noninvasive ultrasound technique that measures small skull expansions with fluctuations in ICP was used to measure cranial oscillations before and near the end of 30-d HDT bed rest in eight healthy, male volunteers. Pulse phase-locked loop (PPLL) output voltage and arterial BP were continuously monitored and correlated. RESULTS: The amplitude of intracranial distance pulsation decreased during 30-d bed rest. Prior to bed rest, the PPLL amplitude was 25 +/- 9 mV and this amplitude was reduced by 60% to 9 +/- 4 mV (a value consistent with that of upright posture) at the end of HDT bed rest (p = 0.01). DISCUSSION: PPLL measurements of skull pulsations are acutely posture dependent, being significantly higher in supine and HDT as compared with upright posture. A cephalad fluid shift is probably the responsible mechanism. Our results indicate that there are adaptations to intracranial pooling of blood and tissue fluid during bed rest that reduce skull pulsation amplitudes to values similar to those obtained in normal upright posture. Detailed studies of the time course of cranial vessel and bone adaptations may provide insights into the potential adaptative mechanisms.

Aerospace Medicine↗
PubMed2003

[Effects of NO synthases inhibitor on cardiovascular deconditioning in rats after 7 d tail-suspension].

OBJECTIVE: To disclose the changes in pathophysiology of cardiovascular deconditioning (CVD) induced by tail-suspension (TS) and to explore the effects of NOS inhibitor on CVD in TS rats. METHOD: -30 degrees tail suspended rats were used as the model to simulate the physiological effects of microgravity. Wistar rats were randomly arranged into: control group (CON), 7 d TS group (TS 7 d) and TS 7 d + NOS inhibitor group (TS 7 d + L-NAME). Then, all the rats were subjected to +90 degrees head-up tilt to simulate the physiological effects of orthostatic stress (SO) after 7 d tail-suspension, only that the TS 7d + L-NAME rats were injected with 10(-6) M L-NAME (N-nitro-L-arginine methylester) through hypoglossal vein before tilting after 7 d TS. Carotid pressure and limb II ECG were measured with a PowerLab physiological system during 120 min tilt, and mean arterial pressure (MAP) and heart rate (HR) were analysized. RESULT: Only one transient episode of hypotension-bradycardia appeared during the tilt in CON rats, but seven episodes occurred in TS 7 d rats, while the TS 7 d + L-NAME rats has only a significant increase in MAP at 10 min. No differences were found between the other parameters in recumbent position and those during the tilt. CONCLUSION: The CVD in the rats induced by TS is relative to an increase of NO production. 10(-6) M L-NAME had an alleviating effects on the CVD, which might be due to the increase of peripheral resistance of blood vessels and the central sympathetic drive by the combination of L-NAME with NOS. The contribution of the perivascular nerves and pulmonary arteries to this effect remains to be further studied.

Animals↗
PubMed2001

Endocrine responses to 7 days of head-down bed rest and orthostatic tests in men and women.

The objective of this study was to investigate plasma volume (PV), total body water, hormones and hydroelectrolyte responses in eight males (25-40 years) and eight females (25-31 years) during 7 days of exposure to simulated microgravity (-6 degrees head-down bed rest, HDBR). Bed rest is a model that has commonly been used to simulate spaceflight. Heart rate (HR), blood pressure (BP) and vasoactive hormone responses were studied before and after HDBR during a 10-min stand test. No change in total body water and body mass was noted in either sex. The decrease in PV was similar in both men (9.1 +/- 1.4%) and women (9.4 +/- 0.8%). Urinary normetanephrine (NMN) was decreased during HDBR in both sexes. Urinary metanephrine (MN) and plasma catecholamines were unchanged. Daily urinary excretion of urea, an indirect index of protein breakdown, was increased only in the female subjects during HDBR. Plasma active renin (AR) and aldosterone were increased in both sexes, but urinary atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were unchanged throughout the study. Also, the hormonal responses to 7 days of HDBR were comparable between men and women. Moreover, the results show similar cardiovascular and endocrine responses to standing after HDBR. However, the orthostatic intolerance following HDBR was associated with a blunted increase in noradrenaline (NA) only in the women during the stand test. It is concluded that: (i) 7 days of physical inactivity achieved during HDBR resulted in a reduced sympathetic activity in both sexes and alterations in protein metabolism in women and (ii) standing after HDBR resulted in an attenuated release of noradrenaline in women.

Adult↗
PubMedDate not supplied

Measurement of hydraulic characteristics of porous media used to grow plants in microgravity.

Understanding the effect of gravity on hydraulic properties of plant growth medium is essential for growing plants in space. The suitability of existing models to simulate hydraulic properties of porous medium is uncertain due to limited understanding of fundamental mechanisms controlling water and air transport in microgravity. The objective of this research was to characterize saturated and unsaturated hydraulic conductivity (K) of two particle-size distributions of baked ceramic aggregate using direct measurement techniques compatible with microgravity. Steady state (Method A) and instantaneous profile measurement (Method B) methods for K were used in a single experimental unit with horizontal flow through thin sections of porous medium providing an earth-based analog to microgravity. Comparison between methods was conducted using a crossover experimental design compatible with limited resources of space flight. Satiated (natural saturation) K ranged from 0.09 to 0.12 cm s-1 and 0.5 to >1 cm s-1 for 0.25- to 1- and 1- to 2-mm media, respectively. The K at the interaggregate/intraaggregate transition was approximately 10(-4) cm s-1 for both particle-size distributions. Significant differences in log(10)K due to method and porous medium were less than one order of magnitude and were attributed to variability in air entrapment. The van Genuchten/Mualem parametric models provided an adequate prediction of K of the interaggregate pore space, using residual water content for that pore space. The instantaneous profile method covers the range of water contents relevant to plant growth using fewer resources than Method A, all advantages for space flight where mass, volume, and astronaut time are limited.

Aluminum Silicates↗
PubMed2003

Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats.

Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P < 0.001) but no effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.

Adaptation, Physiological↗
PubMed2007

Simulated microgravity effects on the rat carotid and femoral arteries: role of contractile protein expression and mechanical properties of the vessel wall.

The goal of this study was to determine the effects of microgravity on myofilament protein expression and both passive and active length-force relationships in carotid and femoral arteries. Microgravity was simulated by 20-day hindlimb unweighting (HU) in Wistar male rats, and carotid and femoral artery segments were isolated from both HU and control (CTL) rats for Western blot and length-force analysis. Western blots revealed that HU significantly decreased myosin light chain-20 (MLC-20) protein levels in both carotid and femoral arteries and decreased myosin heavy chain (MHC) in femoral artery. alpha-Actin levels were not altered by HU treatment in either artery. Length-force analysis demonstrated that HU did not change either passive or active length-force relationships in the femoral artery. HU-treated arterial rings developed significantly less force to 100 mM K(+) than CTL, but optimal lengths were identical. In the carotid artery, length-active force curves were identical for both CTL and HU; however the length-passive force curve for HU-treated rings exhibited a steeper slope than CTL, suggesting decreased compliance of the artery wall. In conclusion, our data suggest that the HU-induced decreases in both MLC-20 and MHC in femoral artery are responsible for the decreased contraction to 100 mM K(+) in HU-treated femoral artery rings. In the carotid artery, the HU-induced decrease in vessel wall compliance may counter any decrease in contractility caused by the decreased MLC-20 levels.

Adaptation, Physiological↗
PubMed2004

Bone cell survival in microgravity: evidence that modeled microgravity increases osteoblast sensitivity to apoptogens.

Studies were performed to evaluate the effects of modeled microgravity on the induction of osteoblast apoptosis. MC3T3-E1 osteoblast-like cells were cultured in alginate carriers in the NASA-approved high aspect ratio vessel (HARV). This system subjects the cells to a time-averaged gravitational field (vector-averaged gravity) to simulate low gravity conditions. Cells were cultured in the HARV for five days, and then examined for apoptosis. In simulated microgravity, the cells remained vital, although analysis of expressed genes indicated that there was loss of the mature osteoblast phenotype. Additionally, we noted that there was a loss of the mitochondrial membrane potential, a low level of the antiapoptotic protein Bcl-2, as well as Akt protein, and the redox status of the cells was disturbed. All of these parameters indicated that vector-averaged gravity disrupts mitochondrial function, thereby sensitizing osteoblasts to apoptosis. We then used a challenge assay to evaluate the apoptotic sensitivity of the cells subjected to vector-averaged gravity. When challenged with staurosporine, cells subjected to vector-averaged gravity evidenced elevated levels of cell death relative to control cell populations. Another objective of the study was to improve upon conventional carriers by using alginate encapsulation to support cells in the HARV. We have demonstrated that the alginate carrier system affords a more robust system than surface-seeded carriers. This new system has the advantage of shielding cells from mechanical damage and fluid shear stresses on cells in the HARV, permitting carefully controlled studies of the effects of vector-averaged gravity.

3T3 Cells↗
PubMed1998

Red cell volume and [erythropoietin] responses during exposure to simulated microgravity.

In order to test the hypothesis that normal gravity is an important influence on human serum [Erythropoietin] ([Epo]), the hematologic response to 16 d of 6 degrees head-down tilt (HDT, n = 6 men) was compared with 16 d of normal gravity exposure (CON, n = 7 men). Prior to bed rest, CON and HDT subjects, respectively, were similar in the following characteristics (mean +/- SD): age = 40 +/- 3, 39 +/- 6 yr; height = 181 +/- 5, 182 +/- 6 cm; weight = 88.5 +/- 11.3, 81.7 +/- 12.0 kg; maximal oxygen consumption in supine 6 degrees head-down tilt position (VO2max) = 2.63 +/- 0.38, 2.67 +/- 0.52 L.min-1; hematocrit = (Hct) 41.6 +/- 2.4, 43.0 +/- 3.4%; hemoglobin ([Hb]) = 15.1 +/- 1.0, 14.5 +/- 1.0 g.100 ml-1; plasma volume (PV) = 3829 +/- 857, 3768 +/- 512 ml; and [Epo] = 11.6 +/- 2.9, 10.0 +/- 6.2 mU.ml-1. Calculated red cell volume (RCV) was greater in HDT than CON (2845 +/- 410 vs. 2139 +/- 253 ml, p < 0.05) at baseline. Decreases in PV (-15%, 580 ml, p < 0.05) and an insignificant decrease in RCV (-12%, 354 ml, p = 0.07) were observed in the HDT group, with a concurrent 6% increase in [Hb] (p < 0.05). PV, RCV and [Hb] remained unchanged in the CON group. [Epo] remained unchanged during HDT (12.2 +/- 3.2; 10.8 +/- 3.8; 11.2 +/- 3.1; 11.2 +/- 2.6 mU.ml-1 for HDT days 1, 2, 8 and 16, respectively). There was no difference between CON and HDT groups in [Epo] before or during HDT. It was concluded that the insignificant change (-12%) in RCV observed during HDT was insufficient to stimulate an increase in [Epo], probably because the content of oxygen in arterial blood remained unaffected. The observation that [Epo] remained unchanged despite this loss of RCV during HDT also suggests a possible decrease in the responsiveness of the erythropoietic system to [Epo].

Adult↗
PubMed2004

Gender differences in organ density in a rat simulated microgravity model.

Research investigating the physiological effects of microgravity on the human body has demonstrated a shift of body fluids in actual spaceflight and in simulated Earth-based microgravity models in both males and females, possibly causing many deleterious physiological effects. Twenty-five anatomically normal female (NF) and 20 ovariectomized (OE) Fischer 344 rats were randomly selected to be in an experimental (1 h of 45 degrees head-down tilt, 45HDT) or control (1 h of prone position) group. At the end of the hour experimental period, the density of the brain, lungs, heart, liver, and left and right kidneys were measured using spiral computed tomography (SCT) while the rats remained in their experimental positions. A sub-group of OE rats (N=6) was administered estrogen replacement therapy on a daily basis (5 micrograms/kg body weight, s.c.) for 4 days and then underwent 1 h of 45HDT and SCT analysis at one day, 2 days, and 5 days to determine if estrogen replacement therapy would alter organ densities. Our data demonstrate that 1 h of 45HDT produced significant increases (p<0.05) in the organ densities of the brain, liver, left kidney, and lung of the OE female group compared to their prone controls. However, only the brain density was significantly increased in the NF group. Estrogen replacement therapy caused a significant decrease in brain organ density at the 5 day time point compared to the 24 h time point. We conclude that estrogen plays a role in fluid distribution in a rat 45HDT model.

Adaptation, Physiological↗
PubMed2001

Use of thigh pressure cuffs to modulate simulated microgravity-induced changes in the skin measured with high-resolution B-scan ultrasound.

OBJECTIVE: The aim of the present study was to evaluate the fluid shift in a simulated microgravity experiment and to test the use of thigh cuffs to help alleviate the problem. METHODS: The change in skin thickness was assessed by a 20 MHz B-scan ultrasound device. This was performed on eight volunteers who underwent two successive 7-day periods of -6 degrees anti-orthostatic bed-rest, with or without the daytime use of thigh cuffs. The thigh cuffs were used to counteract the development of facial oedema. RESULTS: In the control group (without thigh cuffs), the results showed a steady increase in skin thickness of the combined dermis and hypodermis of the forehead and a reduction of the thickness of this tissue on the tibia. For the countermeasure group, although thigh cuffs were only employed during the daytime - being removed at night - their use reduced the amplitude and kinetics of the fluid shift, resulting in greater beneficial effects at the end of the day than early in the morning. CONCLUSION: These results of objective measurements of skin made using a non-invasive high frequency ultrasonography method confirm reports by cosmonauts of a reduction in facial oedema and a more 'comfortable' adaptation to microgravity by the use of thigh cuffs during space flight. This system is potentially promising for investigating fluid shifts in the skin and may prove useful in the evaluation of some oedematous skin diseases, as well as their therapy.

Adult↗
PubMedDate not supplied

Clinical effects of thigh cuffs during a 7-day 6 degrees head-down bed rest.

Thigh cuffs are used by Russian cosmonauts to limit the fluid shift induced by space flight. A ground simulation using the head-down bed rest (HDBR) model was performed to assess the effects of thigh cuffs on clinical tolerance and orthostatic adaptation. 8 male healthy volunteers (32.4 +/- 1.9 years) participated twice in a 7-day HDBR--one time with thigh cuffs (worn daily from 9 am to 7 pm) (TC) and one time without (WTC). Orthostatic tolerance was assessed by a 10 minute stand test and by a LBNP test (5 min at -15, -30, -45 mmHg) before (BDC-1) and at the end of the HDBR period (R+1). Plasma volume was measured before and at the end of HDBR by the Evans blue dye dilution technique. Thigh cuffs limits headache due to fluid shift, as well as the loss in plasma volume (TC: -5.85 +/- 0.95%; WTC: -9.09 +/- 0.82%, p<0.05). The mean duration of the stand test (R+1) did not differ in the two group (TC 7.1 +/- 1.3 min; WTC 7.0 +/- 1.0 min). The increase in HR and decrease in diastolic blood pressure were slightly but significantly larger without thigh cuffs. Duration of the LBNP tests did not differ with thigh cuffs. Thigh cuffs limit the symptoms due to fluid shift and the loss in plasma volume. They partly reduced the increase in HR during orthostatic stress but had no effect on duration of orthostatic stress tests.

Adult↗
PubMedDate not supplied

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey.

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

Aerospace Medicine↗
PubMed2004

Role of individual predisposition in orthostatic intolerance before and after simulated microgravity.

Orthostatic intolerance (OI) is a major problem after spaceflight. Its etiology remains uncertain, but reports have pointed toward an individual susceptibility to OI. We hypothesized that individual predisposition plays an important role in post-bed rest OI. Twenty-four healthy male subjects were equilibrated on a constant diet, after which they underwent tilt-stand test (pre-TST). They then completed 14-16 days of head-down-tilt bed rest, and 14 of the subjects underwent repeat tilt-stand test (post-TST). During various phases, the following were performed: 24-h urine collections and hormonal measurements, plethysmography, and cardiovascular system identification (a noninvasive method to assess autonomic function and separately quantify parasympathetic and sympathetic responsiveness). Development of presyncope or syncope defined OI. During pre-TST, 11 subjects were intolerant and 13 were tolerant. At baseline, intolerant subjects had lower serum aldosterone (P < 0.01), higher excretion of potassium (P = 0.01), lower leg venous compliance (P = 0.03), higher supine parasympathetic responsiveness (P = 0.02), and lower standing sympathetic responsiveness (P = 0.048). Of the 14 subjects who completed post-TST, 9 were intolerant and 5 were tolerant. Intolerant subjects had lower baseline serum cortisol (P = 0.03) and a higher sodium level (P = 0.02) compared with tolerant subjects. Thus several physiological characteristics were associated with increased susceptibility to OI. We propose a new model for OI, whereby individuals with greater leg venous compliance recruit compensatory mechanisms (activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, and withdrawal of the parasympathetic nervous system) in the face of daily postural challenges, which places them at an advantage to face orthostatic stress. With head-down-tilt bed rest, the stimulus to recruit compensatory mechanisms disappears, and differences between the two subgroups attenuate.

Adaptation, Physiological↗
PubMed2005

Influence of 90-day simulated microgravity on human tendon mechanical properties and the effect of resistive countermeasures.

While microgravity exposure is known to cause deterioration of skeletal muscle performance, little is known regarding its effect on tendon structure and function. Hence, the aims of this study were to investigate the effects of simulated microgravity on the mechanical properties of human tendon and to assess the effectiveness of resistive countermeasures in preventing any detrimental effects. Eighteen men (aged 25-45 yr) underwent 90 days of bed rest: nine performed resistive exercise during this period (BREx group), and nine underwent bed rest only (BR group). Calf-raise and leg-press exercises were performed every third day using a gravity-independent flywheel device. Isometric plantar flexion contractions were performed by using a custom-built dynamometer, and ultrasound imaging was used to determine the tensile deformation of the gastrocnemius tendon during contraction. In the BR group, tendon stiffness estimated from the gradient of the tendon force-deformation relation decreased by 58% (preintervention: 124 +/- 67 N/mm; postintervention: 52 +/- 28 N/mm; P < 0.01), and the tendon Young's modulus decreased by 57% postintervention (P < 0.01). In the BREx group, tendon stiffness decreased by 37% (preintervention: 136 +/- 66 N/mm; postintervention: 86 +/- 47 N/mm; P < 0.01), and the tendon Young's modulus decreased by 38% postintervention (P < 0.01). The relative decline in tendon stiffness and Young's modulus was significantly (P < 0.01) greater in the BR group compared with the BREx group. Unloading decreased gastrocnemius tendon stiffness due to a change in tendon material properties, and, although the exercise countermeasures did attenuate these effects, they did not completely prevent them. It is suggested that the total loading volume was not sufficient to completely prevent alterations in tendon mechanical properties.

Adaptation, Physiological↗