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PubMed1996

Lactate uptake by skeletal muscle sarcolemmal vesicles decreases after 4 wk of hindlimb unweighting in rats.

We investigated the effects of 4 wk of hypodynamia on the rate of lactate transport in skeletal muscle sarcolemmal vesicles from control and hindlimb-suspended rats. Characterization of the sarcolemmal preparations was achieved with a marker enzyme (K+-p-nitrophenylphosphatase) and measurement of 1 mM [U-14C]lactate transport activity under zero-trans conditions with or without a pH gradient or the transport inhibitor alpha-hydroxycinnamate. Preparations from the two groups were not significantly different concerning yield and purification. Based on these results, we used this model to analyze the lactate transport activity after hypodynamia by tail suspension. Hindlimb suspension caused a shift from slow to fast myosin heavy chain isoforms in soleus muscles with a 40% decrease in the citrate synthase activity (from 35.3 +/- 3.7 to 21.4 +/- 2.1 mu mol x g-1 x min-1; P < 0.05). Lactate (1 mM) uptake in vesicles from the two groups was a function of time, and the rate after hindlimb suspension was significantly decreased in the suspended compared with the control group (2.25 +/- 0.44 and 3.50 +/- 0.26 nmol x min-1 x mg protein-1, respectively; P < 0.05). These differences were not observed for a higher lactate concentration (50 mM). These results suggest that the level of physical activity plays a role in the regulation of sarcolemmal lactate transport activity implicated in the exchanges of lactate between producing and utilizing cells, organs, and tissues, which are major ways of carbohydrate energy distribution in humans and others species.

4-Nitrophenylphosphatase↗
PubMed1996

Effect of acute head-down tilt on skeletal muscle cross-sectional area and proton transverse relaxation time.

This study investigated changes in skeletal muscle cross-sectional area (CSA) evoked by fluid shifts that accompany short-term 6 degrees head-down tilt (HDT) or horizontal bed rest, the time course of the resolution of these changes after resumption of upright posture, and the effect of altered muscle CSA, in the absence of increased contractile activity, on proton transverse relaxation time (T2). Average muscle (CSA and T2 were determined by standard spin-echo magnetic resonance imaging. Analyses were performed on contiguous transaxial images of the neck and calf. After a day of normal activity, 24 h of HDT increased neck muscle CSA 19 +/- 4(SE)% (P < 0.05) while calf muscle CSA decreased 14 +/- 3% (P < 0.05). The horizontal posture (12 h) induced about one-half of these responses: an 11 +/- 2% (P < 0.05) in the neck muscle CSA and an 8 +/- 2% decrease (P < 0.05) in the calf. Within 2 h after resumption of upright posture, neck and calf muscle CSA returned to within 0.5% (P > 0.05) of the values assessed after a day of normal activity, with most of the change occurring within the first 30 min. No further change in muscle CSA was observed through 6 h of upright posture. Despite these large alterations in muscle CSA, T2 was not altered by more than 1.1 +/- 0.6% (P > 0.05) and did not relate to muscle size. These results suggest that postural manipulations and subsequent fluid shifts modeling micro-gravity elicit marked changes in muscle size. Because these responses were not associated with alterations in muscle T2, it does not appear that simple movement of water into muscle can explain the contrast shift observed after exercise.

Adult↗
PubMed1997

Pulmonary diffusing capacity and pulmonary capillary blood volume during parabolic flights.

Data from the Spacelab Life Sciences-1 (SLS-1) mission have shown sustained but moderate increase in pulmonary diffusing capacity (DL). Because of the occupational constraints of the mission, data were only obtained after 24 h of exposure to microgravity. Parabolic flights are often used to study some effects of microgravity, and we measured changes in DL occurring at the very onset of weightlessness. Measurements of DL, membrane diffusing capacity, and pulmonary capillary blood volume were made in 10 male subjects during the 20-s 0-G phases of parabolic flights performed by the "zero-G" Caravelle aircraft. Using the standardized single-breath technique, we measured DL for CO and nitric oxide simultaneously. We found significant increases in DL for CO (62%), in membrane diffusing capacity for CO (47%), in DL for nitric oxide (47%), and in pulmonary capillary blood volume (71%). We conclude that major changes in the alveolar membrane gas transfers and in the pulmonary capillary bed occur at the very onset of microgravity. Because these changes are much greater than those reported during sustained microgravity, the effects of rapid transition from hypergravity to microgravity during parabolic flights remain questionable.

Acceleration↗
PubMed1997

Atrial distension in humans during microgravity induced by parabolic flights.

The hypothesis was tested that human cardiac filling pressures increase and the left atrium is distended during 20-s periods of microgravity (microG) created by parabolic flights, compared with values of the 1-G supine position. Left atrial diameter (n = 8, echocardiography) increased significantly during microG from 26.8 +/- 1.2 to 30.4 +/- 0.7 mm (P < 0.05). Simultaneously, central venous pressure (CVP; n = 6, transducer-tipped catheter) decreased from 5.8 +/- 1.5 to 4.5 +/- 1.1 mmHg (P < 0.05), and esophageal pressure (EP; n = 6) decreased from 1.5 +/- 1.6 to -4.1 +/- 1.7 mmHg (P < 0.05). Thus transmural CVP (TCVP = CVP - EP; n = 4) increased during microG from 6.1 +/- 3. 2 to 10.4 +/- 2.7 mmHg (P < 0.05). It is concluded that short periods of microG during parabolic flights induce an increase in TCVP and left atrial diameter in humans, compared with the results obtained in the 1-G horizontal supine position, despite a decrease in CVP.

Adult↗
PubMed1998

Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution.

Because resistance exercise (REx) and bed-rest unloading (BRU) are associated with opposing adaptations, our purpose was to test the efficacy of REx against the effects of 14 days of BRU on the knee-extensor muscle group. Sixteen healthy men were randomly assigned to no exercise (NoEx; n = 8) or REx (n = 8). REx performed five sets of leg press exercise with 80-85% of one repetition maximum (1 RM) every other day during BRU. Muscle samples were removed from the vastus lateralis muscle by percutaneous needle biopsy. Myofiber distribution was determined immunohistochemically with three monoclonal antibodies against myosin heavy chain (MHC) isoforms (I, IIa, IIx). MHC distribution was further assessed by quantitative gel electrophoresis. Dynamic 1-RM leg press and unilateral maximum voluntary isometric contraction (MVC) were determined. Maximal neural activation (root mean squared electromyogram) and rate of torque development (RTD) were measured during MVC. Reductions (P < 0.05) in type I (15%) and type II (17%) myofiber cross-sectional areas were found in NoEx but not in REx. Electrophoresis revealed no changes in MHC isoform distribution. The percentage of type IIx myofibers decreased (P < 0.05) in REx from 9 to 2% and did not change in NoEx. 1 RM was reduced (P < 0.05) by 9% in NoEx but was unchanged in REx. MVC fell by 15 and 13% in NoEx and REx, respectively. The agonist-to-antagonist root mean squared electromyogram ratio decreased (P < 0.05) 19% in REx. RTD slowed (P < 0.05) by 54% in NoEx only. Results indicate that REx prevented BRU-induced myofiber atrophy and also maintained training-specific strength. Unlike spaceflight, BRU did not induce shifts in myosin phenotype. The reported benefits of REx may prove useful in prescribing exercise for astronauts in microgravity.

Adult↗
PubMed1998

Choroidal readaptation to gravity in rats after spaceflight and head-down tilt.

To determine when choroidal structures were restored after readaptation to Earth gravity or orthostatic position, fine structure and protein distribution were studied in rat choroid plexus dissected either 6 h [Space Life Sciences-2 (SLS-2) experiments] or 2 days [National Institutes of Health-Rodent 1 (NIH-R1) experiments] after a spaceflight, or 6 h after head-down tilt (HDT) experiments. Apical alterations were noted in choroidal cells from SLS-2 and HDT animals, confirming that weightlessness impaired choroidal structures and functions. However, the presence of small apical microvilli and kinocilia and the absence of vesicle accumulations showed that the apical organization began to be restored rapidly after landing. Very enlarged apical microvilli appeared after 2 days on Earth, suggesting increased choroidal activity. However, as distributions of ezrin and carbonic anhydrase II remained altered in both flight and suspended animals after readaptation to Earth gravity, it was concluded that choroidal structures and functions were not completely restored, even after 2 days in Earth's gravity.

Adaptation, Physiological↗
PubMed1998

Chest wall mechanics in sustained microgravity.

We assessed the effects of sustained weightlessness on chest wall mechanics in five astronauts who were studied before, during, and after the 10-day Spacelab D-2 mission (n = 3) and the 180-day Euromir-95 mission (n = 2). We measured flow and pressure at the mouth and rib cage and abdominal volumes during resting breathing and during a relaxation maneuver from midinspiratory capacity to functional residual capacity. Microgravity produced marked and consistent changes (Delta) in the contribution of the abdomen to tidal volume [DeltaVab/(DeltaVab + DeltaVrc), where Vab is abdominal volume and Vrc is rib cage volume], which increased from 30.7 +/- 3. 5 (SE)% at 1 G head-to-foot acceleration to 58.3 +/- 5.7% at 0 G head-to-foot acceleration (P < 0.005). Values of DeltaVab/(DeltaVab + DeltaVrc) did not change significantly during the 180 days of the Euromir mission, but in the two subjects DeltaVab/(DeltaVab + DeltaVrc) was greater on postflight day 1 than on subsequent postflight days or preflight. In the two subjects who produced satisfactory relaxation maneuvers, the slope of the Konno-Mead plot decreased in microgravity; this decrease was entirely accounted for by an increase in abdominal compliance because rib cage compliance did not change. These alterations are similar to those previously reported during short periods of weightlessness inside aircrafts flying parabolic trajectories. They are also qualitatively similar to those observed on going from upright to supine posture; however, in contrast to microgravity, such postural change reduces rib cage compliance.

Abdomen↗
PubMed1998

Sarcomere lesion damage occurs mainly in slow fibers of reloaded rat adductor longus muscles.

Sarcomere lesions were previously observed with reloading of rat adductor longus muscles after spaceflight and hindlimb unloading (HU). Spaceflown rats displayed more lesioned fibers in the "slow-fiber" region, suggesting a damage-susceptible fiber type. Unloading induces fast myosin expression in some slow fibers, generating hybrid fibers. We examined whether lesion damage differed among slow-, hybrid-, and fast-fiber types in HU-reloaded adductor longus muscles. Temporal HU for 5, 8, 11, 14, and 17 days revealed that hybrid fiber percent, detected by antimyosin immunostaining, peaked at 29 +/- 12% by 14 days. A 14-day HU followed by 12-14 h of voluntary reloading was performed to induce lesions. chi2 analysis showed that slow fibers were preferentially damaged, accounting for 92 +/- 5% of lesioned fibers; hybrid and fast fibers accounted for 7 +/- 4 and <0.5%, respectively. Atrophy did not explain differential lesion damage across fiber types, as slow and hybrid fibers atrophied to a similar extent. Because active myofiber contractions are requisite for lesion formation, selective recruitment of slow fibers most likely explains their damage susceptibility.

Animals↗
PubMed1998

Deposition and dispersion of 1-micrometer aerosol boluses in the human lung: effect of micro- and hypergravity.

We performed bolus inhalations of 1-micrometer particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (microG) and in approximately 1.6 G. Boluses of approximately 70 ml were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 200 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The deposition, dispersion, and position of the bolus in the expired gas were calculated from these data. For Vp >/=400 ml, both deposition and dispersion increased with Vp and were strongly gravity dependent, with the greatest deposition and dispersion occurring for the largest G level. At Vp = 800 ml, deposition and dispersion increased from 33.9% and 319 ml in microG to 56.9% and 573 ml at approximately 1.6 G, respectively (P < 0.05). At each G level, the bolus was expired at a smaller volume than Vp, and this volume became smaller with increasing Vp. Although dispersion was lower in microG than in 1 G and approximately 1.6 G, it still increased steadily with increasing Vp, showing that nongravitational ventilatory inhomogeneity is partly responsible for dispersion in the human lung.

Administration, Inhalation↗
PubMed1999

Influence of brief daily tendon vibration on rat soleus muscle in non-weight-bearing situation.

The purpose of this study was to investigate whether tendon vibration could prevent soleus muscle atrophy during hindlimb unloading (HU). Mechanical vibrations with a constant low amplitude (0.3 mm) were applied (192 s/day) with constant frequency (120 Hz) to the Achilles tendon of the unloaded muscle during the 14-day HU period. Significant reductions in muscle mass (-41%), fiber size, maximal twitch (-54%), and tetanic tensions (-73%) as well as changes in fiber type and electrophoretic profiles and twitch-time parameters (-31% in the contraction time and -30% in the half relaxation time) were found after 14 days of HU when compared with the control soleus. Tendon vibration applied during HU significantly attenuated, but did not prevent, 1) the loss of muscle mass (17 vs. 41%); 2) the decrease in the fiber cross-sectional area of type IIA (-28 vs. -50%) and type IIC (-29 vs. -56%) fibers; and 3) the decrease in maximal twitch (-3 vs. -54%) and maximal tetanic tensions (-29 vs. -73%) and the half relaxation time (1 vs. -30%). Changes in the contraction time and in histological and electrophoretical parameters associated with HU were not counteracted. These findings suggest that tendon vibration can be used as a paradigm to counteract the atrophic process observed after HU.

Animals↗
PubMed1999

Intracellular Ca2+ transients in mouse soleus muscle after hindlimb unloading and reloading.

The objective of this study was to determine whether altered intracellular Ca(2+) handling contributes to the specific force loss in the soleus muscle after unloading and/or subsequent reloading of mouse hindlimbs. Three groups of female ICR mice were studied: 1) unloaded mice (n = 11) that were hindlimb suspended for 14 days, 2) reloaded mice (n = 10) that were returned to their cages for 1 day after 14 days of hindlimb suspension, and 3) control mice (n = 10) that had normal cage activity. Maximum isometric tetanic force (P(o)) was determined in the soleus muscle from the left hindlimb, and resting free cytosolic Ca(2+) concentration ([Ca(2+)](i)), tetanic [Ca(2+)](i), and 4-chloro-m-cresol-induced [Ca(2+)](i) were measured in the contralateral soleus muscle by confocal laser scanning microscopy. Unloading and reloading increased resting [Ca(2+)](i) above control by 36% and 24%, respectively. Although unloading reduced P(o) and specific force by 58% and 24%, respectively, compared with control mice, there was no difference in tetanic [Ca(2+)](i). P(o), specific force, and tetanic [Ca(2+)](i) were reduced by 58%, 23%, and 23%, respectively, in the reloaded animals compared with control mice; however, tetanic [Ca(2+)](i) was not different between unloaded and reloaded mice. These data indicate that although hindlimb suspension results in disturbed intracellular Ca(2+) homeostasis, changes in tetanic [Ca(2+)](i) do not contribute to force deficits. Compared with unloading, 24 h of physiological reloading in the mouse do not result in further changes in maximal strength or tetanic [Ca(2+)](i).

Animals↗
PubMed1999

Surfactant effects in model airway closure experiments.

The capillary instability that occurs on an annular film lining a tube is studied as a model of airway closure. Small waves in the film can amplify and form a plug across the tube. This dynamical behavior is studied using theoretical models and bench-top experiments. Our model predicts the initial growth rate of the instability and its dependence on surfactant effects. In experiments, an annular film is formed by infusion of water into an initially oil-filled glass capillary tube. The thickness of the oil film varies with the infusion flow rate. The instability growth rate and closure time are measured for a range of film thicknesses. Our theory predicts that a thinner film and higher surfactant activity enhance stability; surfactant can decrease the growth rate to 25% of its surfactant-free value. In experiments, we find that surfactant can decrease the growth rate to 20% and increase the closure time by a factor of 3.8. Functional values of a critical film thickness for closure support the theory that it increases in the presence of surfactant.

Animals↗
PubMed1999

Hindlimb unweighting decreases ecNOS gene expression and endothelium-dependent dilation in rat soleus feed arteries.

We tested the hypothesis that hindlimb unweighting (HLU) and the associated reduction in soleus muscle blood flow causes decreased expression of endothelial cell nitric oxide synthase (ecNOS) mRNA and protein and attenuated endothelium-dependent vasodilator responses in rat soleus feed arteries (SFA). Male Sprague-Dawley rats were exposed to HLU (n = 12) or cage control (Con; n = 12) conditions for 14 days. At the end of this period, SFA were isolated, removed, and cannulated with two glass micropipettes for examination of vasodilator responses or frozen for analysis of ecNOS mRNA and protein expression. RT-PCR of RNA from single SFA was used to measure ecNOS mRNA, and immunoblots on single SFAs were used to measure ecNOS protein content. Results revealed that both ecNOS mRNA and ecNOS protein expression were lower in SFA from HLU rats. Dilation to increased intraluminal flow was attenuated in SFA from HLU rats (Con: 88 +/- 8% vs. HLU: 53 +/- 8%) as was maximal vasodilation to acetylcholine (10(-9)-10(-4) M; Con: 88 +/- 5% vs. HLU: 73 +/- 5%). Sensitivity to the endothelium-independent vasodilator sodium nitroprusside (10(-10)-10(-4) M) was enhanced by HLU (EC(50): Con: 4.46 x 10(-7) M vs. HLU: 5.00 x 10(-8) M). Collectively, these data indicate that the chronic reduction in soleus blood flow associated with the reduced physical activity during HLU results in reduced expression of ecNOS mRNA and protein in SFA and attenuated endothelium-dependent vasodilation.

Animals↗
PubMed2001

Maximal instantaneous muscular power after prolonged bed rest in humans.

A reduction in lower limb cross-sectional area (CSA) occurs after bed rest (BR). This should lead to an equivalent reduction in maximal instantaneous muscular power (W(p)) if the body segments' lengths remain unchanged. W(p) was determined during maximal jumps off both feet on a force platform before and on days 2, 6, 10, 32, and 48 after a 42-day duration BR. CSA of thigh muscles was measured by magnetic resonance imaging before and on day 5 after BR. Before BR, W(p) was 3.63 +/- 0.43 kW or 48.6 +/- 3.3 W/kg. On days 2 and 6 after BR, W(p) was reduced by 23.7 +/- 6.9 and 22.7 +/- 5.4% (P < 0.01), respectively. Thigh extensors CSA (CSAEXT) was 16.7 +/- 4.7% (P < 0.01) lower than before. When normalized per CSAEXT, W(p) was reduced by only 4.8 +/- 4.5% (P < 0.05). By day 48 of recovery, W(p) had returned to baseline values. Therefore, if W(p) is appropriately normalized for CSA of the extensor muscles, the reduction in CSAEXT explains most of the decrease in W(p) decrease after BR. Other factors such as a deficit in neural activation or a decrease in fiber-specific tension may account for only 5% of the W(p) loss after BR.

Adult↗
PubMed2001

Expression and functional behavior of troponin C in soleus muscle fibers of rat after hindlimb unloading.

Troponin C (TnC) plays a key role in the regulation of muscle contraction, thereby modulating the Ca(2+)-activation characteristics of skinned muscle fibers. This study was performed to assess the effects of a 15-day hindlimb unloading (HU) period on TnC expression and its functional behavior in the slow postural muscles of the rat. We investigated the TnC isoform expression in whole soleus muscles and in single fibers. The latter were also checked for their Ca(2+) activation characteristics and sensitivity to bepridil, a Ca(2+) sensitizer molecule. This drug has been described as exerting a differential effect on slow and fast fibers, depending on the TnC isoform. With regard to TnC expression, three populations were found in control muscle fibers: slow, hybrid slow, and hybrid fast fibers, with the TnC fast being always coexpressed with TnC slow. In the whole muscle, TnC fast expression increased after HU because of the increase in the proportion of hybrid fast fibers. The HU hybrid fast fibers had properties similar to those of control hybrid fast fibers. The fibers that remained slow after HU exhibited similar bepridil and Sr(2+) properties as control slow fibers. Therefore, in these fibers, the changes could not be related to the TnC molecule.

Animals↗
PubMed2001

Changes in microvascular fluid filtration capacity during 120 days of 6 degrees head-down tilt.

We used venous congestion strain gauge plethysmography (VCP) to measure the changes in fluid filtration capacity (K(f)), isovolumetric venous pressure (Pv(i)), and blood flow in six volunteers before, on the 118th day (D118) of head-down tilt (HDT), and 2 days after remobilization (Post). We hypothesized that 120 days of HDT cause significant micro- and macrovascular changes. We observed a significant increase in K(f) from 3.6 +/- 0.4 x 10(-3) to 5.7 +/- 0.9 x 10(-3) ml. min(-1). 100 ml(-1). mmHg(-1) (+51.4%; P < 0.003), which returned to pretilt values (4.0 + 0.4 x 10(-3) ml. min(-1). 100 ml(-1). mmHg(-1)) after remobilization. Similarly, Pv(i) increased from 13.4 +/- 2.1 mmHg to 28.9 +/- 2.8 mmHg (+105.8%; P < 0.001) at D118 and was not significantly different at Post (12.4 +/- 2.6 mmHg). Blood flow decreased significantly from 2.3 +/- 0.3 to 1.3 +/- 0.2 ml. min(-1). 100 ml tissue(-1) at D118 and was found elevated to 3.4 +/- 0.7 ml. min(-1). 100 ml tissue(-1) at Post. We believe that the increased K(f) is caused by a higher microvascular water permeability. Because this may result in edema formation, it could contribute to the alterations in fluid homeostasis after exposure to microgravity.

Adult↗
PubMed2002

Comparison of acute cardiovascular responses to water immersion and head-down tilt in humans.

The hypothesis was tested that acute water immersion to the neck (WI) compared with 6 degrees head-down tilt (HDT) induces a more pronounced distension of the heart and lower plasma levels of vasoconstrictor hormones. Ten healthy males underwent 30 min of HDT, WI, and a seated control (randomized). During WI, left atrial diameter and stroke volume increased to the same extent as during HDT. Cardiac output increased by 1 l/min more during WI than during HDT. (P < 0.05). Plasma atrial natriuretic peptide increased during WI (P < 0.05) but not during HDT, whereas plasma norepinephrine, vasopressin, and renin activity were suppressed similarly. Mean arterial pressure decreased by 9 mmHg (P < 0.05) during HDT and was unchanged during WI, and heart rate decreased more during HDT (P < 0.05). Arterial pulse pressure increased considerably more during HDT than during WI. In conclusion, the hypothesis was not confirmed because the cardiac atria were similarly distended by acute HDT and WI and the release of vasoconstrictor hormones were suppressed to the same extent.

Adult↗
PubMed2002

Lung function during and after prolonged head-down bed rest.

We determined the effects of prolonged head-down tilt bed rest (HDT) on lung mechanics and gas exchange. Six subjects were studied in supine and upright postures before (control), during [day 113 (D113)], and after (R + number of days of recovery) 120 days of HDT. Peak expiratory flow (PF) never differed between positions at any time and never differed from controls. Maximal midexpiratory flow (FEF(25-75%)) was lower in the supine than in the upright posture before HDT and was reduced in the supine posture by about 20% between baseline and D113, R + 0, and R + 3. The diffusing capacity for carbon monoxide corrected to a standardized alveolar volume (volume-corrected DL(CO)) was lower in the upright than in the supine posture and decreased in both postures by 20% between baseline and R + 0 and by 15% between baseline and R + 15. Pulmonary blood flow (Q(C)) increased from R + 0 to R + 3 by 20 (supine) and 35% (upright). As PF is mostly effort dependent, our data speak against major respiratory muscle deconditioning after 120 days of HDT. The decrease in FEF(25-75%) suggests a reduction in elastic recoil. Time courses of volume-corrected DL(CO) and Q(C) could be explained by a decrease in central blood volume during and immediately after HDT.

Adult↗