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PubMed2006

Objective evaluation of changes in left ventricular and atrial volumes during parabolic flight using real-time three-dimensional echocardiography.

We tested the feasibility of real-time three-dimensional (3D) echocardiographic (RT3DE) imaging to measure left heart volumes at different gravity during parabolic flight and studied the effects of lower body negative pressure (LBNP) as a countermeasure. Weightlessness-related changes in cardiac function have been previously studied during spaceflights using both 2D and 3D echocardiography. Several technical factors, such as inability to provide real-time analysis and the need for laborious endocardial definition, have limited its usefulness. RT3DE imaging overcomes these limitations by acquiring real-time pyramidal data sets encompassing the entire ventricle. RT3DE data sets were obtained (Philips 7500, X3) during breath hold in 16 unmedicated normal subjects in upright standing position at different gravity phases during parabolic flight (normogravity, 1 Gz; hypergravity, 1.8 Gz; microgravity, 0 Gz), with LBNP applied (-50 mmHg) at 0 Gz in selected parabolas. RT3DE imaging during parabolic flight was feasible in 14 of 16 subjects. Data were analyzed (Tomtec) to quantify left ventricular (LV) and atrial (LA) volumes at end diastole and end systole, which significantly decreased at 1.8 Gz and increased at 0 Gz. While ejection fraction did not change with gravity, stroke volume was reduced by 16% at 1.8 Gz and increased by 20% at 0 Gz, but it was not significantly different from 1 Gz values with LBNP. RT3DE during parabolic flight is feasible and provides the basis for accurate quantification of LV and LA volume changes with gravity. As LBNP counteracted the increase of LV and LA volumes caused by changes in venous return, it may be effectively used for preventing cardiac dilatation during 0 Gz.

Adult↗
PubMed2003

Attenuated thermoregulatory sweating and cutaneous vasodilation after 14-day bed rest in humans.

We investigated the effect of head-down bed rest (HDBR) for 14 days on thermoregulatory sweating and cutaneous vasodilation in humans. Fluid intake was ad libitum during HDBR. We induced whole body heating by increasing skin temperature for 1 h with a water-perfused blanket through which hot water (42 degrees C) was circulated. The experimental room was air-conditioned (27 degrees C, 30-40% relative humidity). We measured skin blood flow (chest and forearm), skin temperatures (chest, upper arm, forearm, thigh, and calf), and tympanic temperature. We also measured sweat rate by the ventilated capsule method in which the skin area for measurement was drained by dry air conditioned at 27 degrees C under similar skin temperatures in both trials. We calculated cutaneous vascular conductance (CVC) from the ratio of skin blood flow to mean blood pressure. From tympanic temperature-sweat rate and -CVC relationships, we assessed the threshold temperature and sensitivity as the slope response of variables to a given change in tympanic temperature. HDBR increased the threshold temperature for sweating by 0.31 degrees C at the chest and 0.32 degrees C at the forearm, whereas it reduced sensitivity by 40% at the chest and 31% at the forearm. HDBR increased the threshold temperature for cutaneous vasodilation, whereas it decreased sensitivity. HDBR reduced plasma volume by 11%, whereas it did not change plasma osmolarity. The increase in the threshold temperature for sweating correlated with that for cutaneous vasodilation. In conclusion, HDBR attenuated thermoregulatory sweating and cutaneous vasodilation by increasing the threshold temperature and decreasing sensitivity. HDBR increased the threshold temperature for sweating and cutaneous vasodilation by similar magnitudes, whereas it decreased their sensitivity by different magnitudes.

Adolescent↗
PubMed2003

Exercise throughout 6 degrees head-down tilt bed rest preserves thermoregulatory responses.

Spaceflight and its bed rest analog [6 degrees head-down tilt (HDT)] decrease plasma and blood volume and aerobic capacity. These responses may be associated with impaired thermoregulatory responses observed during exercise and passive heating after HDT exposure. This project tested the hypothesis that dynamic exercise during 13 days of HDT bed rest preserves thermoregulatory responses. Throughout HDT bed rest, 10 subjects exercised for 90 min/day (75% of pre-HDT maximum heart rate; supine). Before and after HDT bed rest, each subject exercised in the supine position at the same workload in a 28 degrees C room. The internal temperature (Tcore) threshold for the onset of sweating and cutaneous vasodilation, as well as the slope of the relationship between the elevation in Tcore relative to the elevation in sweat rate (SR) and cutaneous vascular conductance (CVC; normalized to local heating maximum), were quantified pre- and post-HDT. Tcore thresholds for the onset of cutaneous vasodilation on the chest and forearm (chest: 36.79 +/- 0.12 to 36.94 +/- 0.13 degrees C, P = 0.28; forearm: 36.76 +/- 0.12 to 36.91 +/- 0.11 degrees C, P = 0.16) and slope of the elevation in CVC relative to Tcore (chest: 77.9 +/- 14.2 to 80.6 +/- 17.2%max/ degrees C; P = 0.75; forearm: 76.3 +/- 11.8 to 67.5 +/- 14.3%max/ degrees C, P = 0.39) were preserved post-HDT. Moreover, the Tcore threshold for the onset of SR (36.66 +/- 0.12 to 36.74 +/- 0.10 degrees C; P = 0.36) and the slope of the relationship between the elevation in SR and the elevation in Tcore (1.23 +/- 0.19 to 1.01 +/- 0.14 mg x cm(-2) x min(-1) x degrees C(-1); P = 0.16) were also maintained. Finally, after HDT bed rest, peak oxygen uptake and plasma and blood volumes were not different relative to pre-HDT bed rest values. These data suggest that dynamic exercise during this short period of HDT bed rest preserves thermoregulatory responses.

Adult↗
PubMed2005

Intensive exercise training suppresses testosterone during bed rest.

Spaceflight and prolonged bed rest (BR) alter plasma hormone levels inconsistently. This may be due, in part, to prescription of heavy exercise as a countermeasure for ameliorating the adverse effects of disuse. The initial project was to assess exercise programs to maintain aerobic performance and leg strength during BR. The present study evaluates the effect of BR and the performance of the prescribed exercise countermeasures on plasma steroid levels. In a 30-day BR study of male subjects, the efficacy of isotonic (ITE, n = 7) or isokinetic exercise (IKE, n = 7) training was evaluated in contrast to no exercise (n = 5). These exercise countermeasures protected aerobic performance and leg strength successfully. BR alone (no-exercise group) did not change steroidogenesis, as assessed by the plasma concentrations of cortisol, progesterone, aldosterone, and free (FT) and total testosterone (TT). In the exercise groups, both FT and TT were decreased (P < 0.05): FT during IKE from 24 +/- 1.7 to 18 +/- 2.0 pg/ml and during ITE from 21 +/- 1.5 to 18 +/- 1 pg/ml, and TT during IKE from 748 +/- 68 to 534 +/- 46 ng/dl and during ITE from 565 +/- 36 to 496 +/- 38 ng/dl. The effect of intensive exercise countermeasures on plasma testosterone was not associated with indexes of overtraining. The reduction in plasma testosterone associated with both the IKE and ITE countermeasures during BR supports our hypothesis that intensive exercise countermeasures may, in part, contribute to changes in plasma steroid concentrations during spaceflight.

Adaptation, Physiological↗
PubMed2005

Regional difference of blood flow in anesthetized rats during reduced gravity induced by parabolic flight.

To examine a hypothesis that change in regional blood flow due to decreased hydrostatic pressure gradient and redistribution of blood during reduced gravity (rG) is different between organs, changes in cerebrocortical blood flow (CBF) and blood flow in the temporal muscle (MBF) with exposure to rG were measured in anesthetized rats in head-up tilt and flat positions during parabolic flight. Carotid arterial pressure (CAP), jugular venous pressure (JVP), and abdominal aortic pressure were also measured simultaneously. In the head-up tilt group, CBF increased by 15 +/- 3% within 3 s of entry into rG and rapidly recovered during rG. MBF also increased, but the change was significantly greater than that of CBF. JVP increased by 1.8 +/- 0.5 mmHg, probably due to loss of hydrostatic pressure gradient, since the measuring point of JVP was 2-3 cm above the hydrostatic indifference point. CAP and abdominal aortic pressure increased by 16.7 +/- 2 and 7.7 +/- 2 mmHg, respectively, compared with the 1-G condition. Muscle vascular resistance [(CAP-JVP)/MBF] decreased on entry into rG, but no significant change was observed in cerebrocortical vascular resistance [(CAP-JVP)/CBF]. In the flat group, no significant change was observed in all the variables. The results indicate that arteriolar vasodilatation occurs in the temporal muscle but not in the cerebral cortex. Thus the blood flow control mechanism at the onset of rG is different between intra- and extracranial organs.

Adaptation, Physiological↗
PubMed2003

Skeletal muscle unweighting: spaceflight and ground-based models.

Long-term manned spaceflight requires that flight crews be exposed to extended periods of unweighting of antigravity skeletal muscles. This exposure will result in adaptations in these muscles that have the potential to debilitate crew members on return to increased gravity environments. Therefore, the development of countermeasures to prevent these unwanted adaptations is an important requirement. The limited access to microgravity environments for the purpose of studying muscle adaptation and evaluating countermeasure programs has necessitated the use of ground-based models to conduct both basic and applied muscle physiology research. In this review, the published results from ground-based models of muscle unweighting are presented and compared with the results from related spaceflight research. The models of skeletal muscle unweighting with a sufficient body of literature included bed rest, cast immobilization, and unilateral lower limb suspension. Comparisons of changes in muscle strength and size between these models in the context of the limited results available from spaceflight suggest that each model may be useful for the investigation of certain aspects of the skeletal muscle unweighting that occur in microgravity.

Animals↗
PubMed2005

Dynamic culture in a rotating-wall vessel bioreactor differentially inhibits murine T-lymphocyte activation by mitogenic stimuli upon return to static conditions in a time-dependent manner.

Depressed immune function is a well-documented effect of spaceflight. Both in-flight studies and ground-based studies using microgravity analogs, such as rotating wall vessel (RWV) bioreactors, have demonstrated that mitogen-stimulated T lymphocytes exhibit decreased proliferation, IL-2 secretion, and activation marker expression in true microgravity and the dynamic RWV-culture environment. This study investigates the kinetics of RWV-induced T lymphocyte inhibition by monitoring the ability of Balb/c mouse splenocytes to become activated under static culture conditions after concanavalin A (Con A) stimulation in an RWV. Splenocytes were stimulated with Con A and cultured for up to 24 h in the RWV before being allowed to "recover" under static culture conditions in the continued presence of Con A. The T-lymphocyte fraction of splenocytes was assayed during the recovery period for IL-2 secretion, expansion of the T-lymphocyte population, and expression of the activation marker CD25. Our results indicate that CD25 expression was not affected by any duration of RWV exposure. In contrast, proliferation and IL-2 secretion were inhibited by >8 and 12 h of exposure, respectively. Culture in the RWV for 24 h resulted in a near-complete loss of cellular viability during the recovery period, which was not seen in cells maintained in the RWV for 16 h or less. Taken together, these results indicate that for up to 8 h of RWV culture activation is not significantly impaired upon return to static conditions; longer duration RWV culture results in a gradual loss of activation during the recovery period most likely because of decreased T-cell viability and/or IL-2 production.

Animals↗
PubMed2003

Enhanced sympathoinhibitory response to volume expansion in conscious hindlimb-unloaded rats.

Prolonged exposure to microgravity or bed rest produces cardiovascular deconditioning, which is characterized by reductions in plasma volume, alterations in autonomic function, and a predisposition toward orthostatic intolerance. Although the precise mechanisms have not been fully elucidated, it is possible that augmented cardiopulmonary reflexes contribute to some of these effects. The purpose of the present study was to test the hypothesis that sympathoinhibitory responses to volume expansion are enhanced in the hindlimb-unloaded (HU) rat, a model of cardiovascular deconditioning. Mean arterial blood pressure, heart rate, and renal sympathetic nerve activity (RSNA) responses to isotonic volume expansion (0.9% saline iv, 15% of plasma volume over 5 min) were examined in conscious HU (14 days) and control animals. Volume expansion produced decreases in RSNA in both groups; however, this effect was significantly greater in HU rats (-46 +/- 7 vs. -25 +/- 4% in controls). Animals instrumented for central venous pressure (CVP) did not exhibit differences in CVP responses to volume expansion. These data suggest that enhanced cardiopulmonary reflexes may be involved in the maintenance of reduced plasma volume and contribute to attenuated baroreflex-mediated sympathoexcitation after spaceflight or bed rest.

Animals↗
PubMed2002

Nonuniform changes in arteriolar myogenic tone within skeletal muscle following hindlimb unweighting.

Hindlimb unweighting (HLU) has been shown to alter myogenic tone distinctly in arterioles isolated from skeletal muscles composed predominantly of fast-twitch (white gastrocnemius) compared with slow-twitch (soleus) fibers. Based on these findings, we hypothesized that HLU would alter myogenic tone differently in arterioles isolated from distinct fiber-type regions within a single skeletal muscle. We further hypothesized that alterations in myogenic tone would be associated with alterations in voltage-gated Ca(2+) channel current (VGCC) density of arteriolar smooth muscle. After 14 days of HLU or weight bearing (control), first-order arterioles were isolated from both fast-twitch and mixed fiber-type regions of the gastrocnemius muscle, cannulated, and pressurized at 90 cmH(2)O. Mixed gastrocnemius arterioles of HLU rats demonstrated increased spontaneous tone [43 +/- 5% (HLU) vs. 27 +/- 4% (control) of possible constriction] and an approximately twofold enhanced myogenic response when exposed to step changes in intraluminal pressure (10-130 cmH(2)O) compared with control rats. In contrast, fast-twitch gastrocnemius arterioles of HLU rats demonstrated similar levels of spontaneous tone [6 +/- 2% (HLU) vs. 6 +/- 2% (control)] and myogenic reactivity to control rats. Neither KCl-induced contractile responses (10-50 mM KCl) nor VGCC density was significantly different between mixed gastrocnemius arterioles of HLU and control rats. These results suggest that HLU produces diverse adaptations in myogenic reactivity of arterioles isolated from different fiber-type regions of a single skeletal muscle. Furthermore, alterations in myogenic responses were not attributable to altered VGCC density.

Adaptation, Physiological↗
PubMed2002

Effects of microgravity elicited by parabolic flight on abdominal aortic pressure and heart rate in rats.

Abdominal aortic pressure (AAP), heart rate (HR), and aortic nerve activity (ANA) during parabolic flight were measured by using a telemetry system to clarify the acute effect of microgravity (microG) on hemodynamics in rats. While the animals were conscious, AAP increased up to 119 +/- 3 mmHg on exposure to microG compared with the value at 1 G (95 +/- 3 mmHg; P < 0.001), whereas AAP decreased immediately on exposure to microG under urethane anesthesia (microG: 72 +/- 9 mmHg vs. 1 G: 78 +/- 8 mmHg; P < 0.05). HR also increased during microG in conscious animals (microG: 349 +/- 12 beats/min vs. 1 G: 324+9 beats/min; P < 0.01), although no change was observed under anesthesia. ANA, which was measured under anesthesia, decreased in response to acute microG exposure (microG: 33 +/- 7 counts/s vs. 1 G: 49 +/- 5 counts/s; P < 0.01). These results suggest that microG essentially induces a decrease of arterial pressure; however, emotional stress and body movements affect the responses of arterial pressure and HR during exposure to acute microG.

Aircraft↗
PubMed2002

Unilateral lower limb suspension does not mimic bed rest or spaceflight effects on human muscle fiber function.

We used Ca2+-activated skinned muscle fibers to test the hypothesis that unilateral lower leg suspension (ULLS) alters cross-bridge mechanisms of muscle contraction. Soleus and gastrocnemius biopsies were obtained from eight subjects before ULLS, immediately after 12 days of ULLS (post-0 h), and after 6 h of reambulation (post-6 h). Post-0 h soleus fibers expressing type I myosin heavy chain (MHC) showed significant reductions in diameter, absolute and specific peak Ca2+-activated force, unloaded shortening velocity, and absolute and normalized peak power. Fibers obtained from the gastrocnemius were less affected by ULLS, particularly fibers expressing fast MHC isoforms. Post-6 h soleus fibers produced less absolute and specific peak force than did post-0 h fibers, suggesting that reambulation after ULLS induced cell damage. Like bed rest and spaceflight, ULLS primarily affects soleus over gastrocnemius fibers. However, in contrast to these other models, slow soleus fibers obtained after ULLS showed a decrease in unloaded shortening velocity and a greater reduction in specific force.

Adult↗
PubMed2004

Modeled microgravity-induced protein kinase C isoform expression in human lymphocytes.

In long-term space travel, the crew is exposed to microgravity and radiation that invoke potential hazards to the immune system. T cell activation is a critical step in the immune response. Receptor-mediated signaling is inhibited in both microgravity and modeled microgravity (MMG) as reflected by diminished DNA synthesis in peripheral blood lymphocytes and their locomotion through gelled type I collagen. Direct activation of protein kinase C (PKC) bypassing cell surface events using the phorbol ester PMA rescues MMG-inhibited lymphocyte activation and locomotion, whereas the calcium ionophore ionomycin had no rescue effect. Thus calcium-independent PKC isoforms may be affected in MMG-induced locomotion inhibition and rescue. Both calcium-dependent isoforms and calcium-independent PKC isoforms were investigated to assess their expression in lymphocytes in 1 g and MMG culture. Human lymphocytes were cultured and harvested at 24, 48, 72, and 96 h, and serial samples were assessed for locomotion by using type I collagen and expression of PKC isoforms. Expression of PKC-alpha, -delta, and -epsilon was assessed by RT-PCR, flow cytometry, and immunoblotting. Results indicated that PKC isoforms delta and epsilon were downregulated by >50% at the transcriptional and translational levels in MMG-cultured lymphocytes compared with 1-g controls. Events upstream of PKC, such as phosphorylation of phospholipase Cgamma in MMG, revealed accumulation of inactive enzyme. Depressed calcium-independent PKC isoforms may be a consequence of an upstream lesion in the signal transduction pathway. The differential response among calcium-dependent and calcium-independent isoforms may actually result from MMG intrusion events earlier than PKC, but after ligand-receptor interaction.

Cells, Cultured↗
PubMed2005

Residual heterogeneity of intra- and interregional pulmonary perfusion in short-term microgravity.

We hypothesized that the perfusion heterogeneity in the human, upright lung is determined by nongravitational more than gravitational factors. Twelve and six subjects were studied during two series of parabolic flights. We used cardiogenic oscillations of O(2)/SF(6) as an indirect estimate of intraregional perfusion heterogeneity (series 1) and phase IV amplitude (P(4)) as a indirect estimate of interregional perfusion heterogeneity (series 2). A rebreathing-breath holding-expiration maneuver was performed. In flight, breath holding and expiration were performed either in microgravity (0 G) or in hypergravity. Controls were performed at normal gravity (1 G). In series 1, expiration was performed at 0 G. Cardiogenic oscillations of O(2)/SF(6) were 19% lower when breath holding was performed at 0 G than when breath holding was performed at 1 G [means (SD): 1.7 (0.3) and 2.3 (0.6)% units] (P = 0.044). When breath holding was performed at 1.8 G, values did not differ from 1-G control [2.6 (0.8)% units, P = 0.15], but they were 17% larger at 1.8 G than at 1 G. In series 2, expiration was performed at 1.7 G. P(4) changed with gravity (P < 0.001). When breath holding was performed at 0 G, P(4) values were 45 (46)% of control. When breath holding was performed at 1.7 G, P(4) values were 183 (101)% of control. We conclude that more than one-half of indexes of perfusion heterogeneity at 1 G are caused by nongravitational mechanisms.

Adaptation, Physiological↗
PubMed1996

Is the regulation of the center of mass maintained during leg movement under microgravity conditions?

1. Investigations on stance regulation have already suggested that the body's center of mass is the variable controlled by the CNS to maintain equilibrium. The aim of this study was to determine how the center of mass of the body is regulated when leg movements are made under different gravitoinertial force conditions. 2. Kinematic and electromyographic (EMG) recordings were made during both straight-and-level flight (earth-normal gravity condition, nG) and periods of weightlessness in parabolic flight (microgravity condition, microG). The standing subjects were restrained to the floor (kept from floating away in microG) and were instructed to raise one leg laterally to an angle of 45 degrees as fast as possible. 3. Two modes of center of mass (CM) control were identified during leg movement in nG: a "shift mode" and a "stabilization mode." The shift mode served to transfer the CM toward the supporting side before the leg raising, and it preceded the phase of single limb support. The stabilization mode took place after the CM shift was completed and was aimed at stabilizing the CM during raising of the leg. In this phase, the movement of the raising leg is counterbalanced by a lateral inclination of the trunk in the opposite direction. As a consequence, CM position did not change with respect to the position reached before the leg raising, and its projection on the ground remained within the support area delineated by the stance foot. 4. Under microG, the CM position did not change before the leg raising. Moreover, gastrocnemius medialis activity observed in the moving leg under nG, preceding the initiation of the body weight transfer toward the supporting leg, was greatly reduced. While the leg is raising, the simultaneous and opposite lateral trunk movement was still present in microG. 5. Results suggest that the body weight transfer corresponding to the shift mode, might depend on the gravity constraints, whereas the stabilization mode, which remains unchanged in microG, might be a motor stereotype that does not depend on the gravity conditions.

Adult↗