Beta-blockade does not improve orthostatic intolerance induced by 20 days bed rest

To assess if propranolol influences orthostatic intolerance induced by prolonged bed rest (BR), a lower body negative pressure test (LBNP) and left ventricular (LV) echocardiography before and during -40mmHg of LBNP were performed with and without intravenous propranolol administration (0.04mg/kg) in 9 healthy volunteers (mean age: 21 years) before and after 20 days BR. LBNP tolerance time (LBNP-T), endpoint heart rate(HR), and percentage changes from 0 to -40mmHg LBNP in HR, LV diastolic dimension(LVDd), stroke volume (SV), cardiac output (CO), and systemic vascular resistance(SVR) were measured. After BR, percentage changes in CO during LBNP was not altered by propranolol (-12+/-21% vs. -24+/-24%; with and without propranolol; p>0.05) because the effect on percentage changes in HR (18+/-11% vs. 26+/-12%; p<0.05) cancelled out the effects of percentage changes in LVDd (-9+/-6% vs. -15+/-10%; p<0.05) and percentage changes in SV (-26+/-16% vs. -39+/-22%; p<0.05). In addition, propranolol decreased end-point HR (85+/-15bpm vs. 119+/-l4bpm; p<0.05) and percentage changes in SVR (25+/-32% vs. 53+/-57%; p<0.05). As a result, LBNP-T after BR was unchanged by propranolol (8.8+/-3.3min vs. 10.8+/-5.0min; p>0.05). In conclusion, propranolol failed to change orthostatic intolerance induced by BR.     

Attenuated sympathetic nerve responses after 24 hours of bed rest

Bed rest reduces orthostatic tolerance. Despite decades of study, the cause of this phenomenon remains unclear. In this report we examined hemodynamic and sympathetic nerve responses to graded lower body negative pressure (LBNP) before and after 24 h of bed rest. LBNP allows for baroreceptor disengagement in a graded fashion. We measured heart rate (HR), cardiac output (HR x stroke volume obtained by echo Doppler), and muscle sympathetic nerve activity (MSNA) during a progressive and graded LBNP paradigm. Negative pressure was increased by 10 mmHg every 3 min until presyncope or completion of -60 mmHg. After bed rest, LBNP tolerance was reduced in 11 of 13 subjects (P <.023), HR was greater (P <.002), cardiac output was unchanged, and the ability to augment MSNA at high levels of LBNP was reduced (rate of rise for 30- to 60-mmHg LBNP before bed rest 0.073 bursts x min(-1) x mmHg(-1); after bed rest 0.035 bursts x min(-1) x mmHg(-1); P < 0.016). These findings suggest that 24 h of bed rest reduces sympathetic nerve responses to LBNP.     

Prolonged bed rest impairs response of the small arteries to cold pressor test

Cold pressor test (CPT) has been known to increase vascular resistance through adrenergic stimulation. To assess the effect of prolonged bed rest (BR) on sympathetic neural control, blood flow velocity of the proper palmar digital artery (resistance vessel) was measured in 10 healthy volunteers during a 90 seconds CPT by pulsed Doppler ultrasound using a 7.5 MHz linear transducer before and after 20 days BR. Blood flow velocity in the proper palmar digital artery decreased during the first half of the CPT both before and after BR, but decreases in peak flow velocity became less prominent (p<0.05) after BR (-48+/-20%) than before bed rest (-61+/-25%). The only subject whose lower body negative pressure tolerance time was prolonged after BR showed prominent decreases in peak flow velocity during the first half of the CPT after BR. Peak flow velocity returned to the pre-test value during the latter half of the CPT in 7 subjects before BR, but in only 2 subjects after BR (p<0.05). Thus, 20 days BR impairs the response of the small digital arteries to CPT, suggesting that a decrease in a adrenergic stimulation occurs after prolonged BR.     

Exercise plus volume loading prevents orthostatic intolerance but not reduction in cerebral blood flow velocity after bed rest

This study tested the hypothesis that reduction in cerebral blood flow (CBF) during orthostatic stress after bed rest can be ameliorated with volume loading, exercise, or both. Transcranial Doppler was used to measure changes in CBF velocity during lower body negative pressure (LBNP) before and after an 18-day bed rest in 33 healthy subjects. Subjects were assigned into four groups with similar age and sex: 1) supine cycling during bed rest (Exercise group; n = 7), 2) volume loading with Dextran infusion after bed rest to restore reduced left ventricular filling pressure (Dextran group; n = 7), 3) exercise combined with volume loading to prevent orthostatic intolerance (Ex-Dex group; n = 7), and 4) a control group (n = 12). LBNP tolerance was measured using a cumulative stress index (CSI). After bed rest, CBF velocity was reduced at a lower level of LBNP in the Control group, and the magnitude of reduction was greater in the Ex-Dex group. However, reduction in orthostatic tolerance was prevented in the Ex-Dex group. Notably, volume loading alone prevented greater reductions in CBF velocity after bed rest, but CSI was reduced still by 25%. Finally, decreases in CBF velocity during LBNP were correlated with reduction in cardiac output under all conditions (r(2) = 0.86; P = < 0.001). Taken together, these findings demonstrate that volume loading alone can ameliorate reductions in CBF during LBNP. However, the lack of associations between changes in CBF velocity and orthostatic tolerance suggests that reductions in CBF during LBNP under steady-state conditions by itself are unlikely to be a primary factor leading to orthostatic intolerance.     

Lower body negative pressure exercise plus brief postexercise lower body negative pressure improve post-bed rest orthostatic tolerance.

Orthostatic intolerance follows actual weightlessness and weightlessness simulated by bed rest. Orthostasis immediately after acute exercise imposes greater cardiovascular stress than orthostasis without prior exercise. We hypothesized that 5 min/day of simulated orthostasis [supine lower body negative pressure (LBNP)] immediately following LBNP exercise maintains orthostatic tolerance during bed rest. Identical twins (14 women, 16 men) underwent 30 days of 6 degrees head-down tilt bed rest. One of each pair was randomly selected as a control, and their sibling performed 40 min/day of treadmill exercise while supine in 53 mmHg (SD 4) [7.05 kPa (SD 0.50)] LBNP. LBNP continued for 5 min after exercise stopped. Head-up tilt at 60 degrees plus graded LBNP assessed orthostatic tolerance before and after bed rest. Hemodynamic measurements accompanied these tests. Bed rest decreased orthostatic tolerance time to a greater extent in control [34% (SD 10)] than in countermeasure subjects [13% (SD 20); P < 0.004]. Controls exhibited cardiac stroke volume reduction and relative cardioacceleration typically seen after bed rest, yet no such changes occurred in the countermeasure group. These findings demonstrate that 40 min/day of supine LBNP treadmill exercise followed immediately by 5 min of resting LBNP attenuates, but does not fully prevent, the orthostatic intolerance associated with 30 days of bed rest. We speculate that longer postexercise LBNP may improve results. Together with our earlier related studies, these ground-based results support spaceflight evaluation of postexercise orthostatic stress as a time-efficient countermeasure against postflight orthostatic intolerance.     

Effect of lower body negative pressure on orthostatic tolerance and cardiac function during 21 days head-down tilt bed rest

The purpose of the present study was to investigate the changes of orthostatic tolerance and cardiac function during 21 d head-down tilt (HDT) bed rest and effect of lower body negative pressure in the first and the last week in humans. Twelve healthy male volunteers were exposed to -6 degrees HDT bed rest for 21 d. Six subjects received -30 mmHg LBNP sessions for 1 h per day from the 1st to the 7th day and from the 15th to the 21st day of the HDT, and six others served as control. Orthostatic tolerance was assessed by means of standard tilt test. Stroke volume (SV), cardiac output (CO), preejection period (PEP) and left ventricular ejection time (LVET) were measured before and during HDT. Before HDT, all the subjects in the two groups completed the tilt tests. After 10 d and 21 d of HDT, all the subjects of the control group and one subject of the LBNP group could not complete the tilt test due to presyncopal or syncopal symptoms. The mean upright time in the control group (15.0 +/- 3.2 min) was significantly shorter than those in the LBNP group (19.7 +/- 0.9 min). SV and CO decreased significantly in the control group on days 3 and 10 of HDT, but remained unchanged throughout HDT in the LBNP group. A significant increase in PEP/LVET was observed on days 3 and 14 of HDT in both groups. The PEP/LVET in the LBNP group was significantly lower on day 3 of HDT, while LVET in the LBNP group was significantly higher on days 3, 7 and 14 of HDT than those in the control group. The results of this study suggest that brief daily LBNP sessions used in the first and the last weeks of 21 d HDT bed rest were effective in diminished the effect of head-down tilt on orthostatic tolerance, and LBNP might partially improve cardiac pumping function and cardiac systole function.     

卧床前后压力感受性反射机能变化的研究

许多数据表明长期失重以后立位耐力降低可能与压力感受性反射功能的改变有关。本文比较了两组被试者15天低动力卧床前后的立位耐力。以血压调节模型为基础分析了两种不同方式卧床前后单纯立位和下身负压加立位时压力感受性反射功能的改变,并用颈部加压及下身负压对中枢调节功能改变进行了观察。结果表明严格的头低位卧床后,立位耐力下降及压力感受性反射功能改变明显大于半日平卧半日倚坐者。而压力感受性反射功能的改变,特别是中枢神经系统调节功能的紊乱,是卧床后立位耐力降低的主要原因。从这种考虑为基础,作者提出了改变失重或模拟失重状态下的血液分布,调整对压力感受器的刺激,可能是预防心血管失调的有效方法。     

Central volume expansion is pivotal for sustained decrease in heart rate during seated to supine posture change

During prolonged, static carotid baroreceptor stimulation by neck suction (NS) in seated humans, heart rate (HR) decreases acutely and thereafter gradually increases. This increase has been explained by carotid baroreceptor adaptation and/or buffering by aortic reflexes. During a posture change from seated to supine (Sup) with similar carotid stimulation, however, the decrease in HR is sustained. To investigate whether this discrepancy is caused by changes in central blood volume, we compared (n = 10 subjects) the effects of 10 min of seated NS (adjusted to simulate carotid stimulation of a posture change), a posture change from seated to Sup, and the same posture change with left atrial (LA) diameter maintained unchanged by lower body negative pressure (Sup + LBNP). During Sup, the prompt decreases in HR and mean arterial pressure (MAP) were sustained. HR decreased similarly within 30 s of NS (65 +/- 2 to 59 +/- 2 beats/min) and Sup + LBNP (65 +/- 2 to 58 +/- 2 beats/min) and thereafter gradually increased to values of seated. MAP decreased similarly within 5 min during Sup + LBNP and NS (by 7 +/- 1 to 9 +/- 1 mmHg) and thereafter tended to increase toward values of seated subjects. Arterial pulse pressure was increased the most by Sup, less so by Sup + LBNP, and was unchanged by NS. LA diameter was only increased by Sup. In conclusion, static carotid baroreceptor stimulation per se causes the acute (<30 s) decrease in HR during a posture change from seated to Sup, whereas the central volume expansion (increased LA diameter and/or arterial pulse pressure) is pivotal to sustain this decrease. Thus the effects of central volume expansion override adaptation of the carotid baroreceptors and/or buffering of aortic reflexes.     

Regulation of muscle sympathetic nerve activity after bed rest deconditioning

Cardiovascular deconditioning reduces orthostatic tolerance. To determine whether changes in autonomic function might produce this effect, we developed stimulus-response curves relating limb vascular resistance, muscle sympathetic nerve activity (MSNA), and pulmonary capillary wedge pressure (PCWP) with seven subjects before and after 18 days of -6 degrees head-down bed rest. Both lower body negative pressure (LBNP; -15 and -30 mmHg) and rapid saline infusion (15 and 30 ml/kg body wt) were used to produce a wide variation in PCWP. Orthostatic tolerance was assessed with graded LBNP to presyncope. Bed rest reduced LBNP tolerance from 23.9 +/- 2.1 to 21.2 +/- 1.5 min, respectively (means +/- SE, P = 0.02). The MSNA-PCWP relationship was unchanged after bed rest, though at any stage of the LBNP protocol PCWP was lower, and MSNA was greater. Thus bed rest deconditioning produced hypovolemia, causing a shift in operating point on the stimulus-response curve. The relationship between limb vascular resistance and MSNA was not significantly altered after bed rest. We conclude that bed rest deconditioning does not alter reflex control of MSNA, but may produce orthostatic intolerance through a combination of hypovolemia and cardiac atrophy.     

Regional changes in muscle mass and strength following 20 days of bed rest, and the effects on orthostatic tolerance capacity in young subjects

To this day, many studies have suggested that prolonged bed rest (BR) affects on muscle mass and strength not only in gravity muscles but also in ungravity muscles. However, it is still unclear whether the decrease in regional muscle strength after BR is due to the alterations in the corresponding muscle mass, or not. On the other hand, if BR decreases the mass of antigravity muscles (UGM) as well as muscle strength and then increases tissue compliance of the antigravity muscles, orthostatic tolerance capacity will be decreased by the reduction in cardiac output (CO) in spite of the increase in myocardial contractility because the more decrease in venous return due to the more increase in blood pooling within the compliant tissues of the lower body. However, this is also unclear. To make these questions clear, the present study investigated the regional muscle mass and strength and orthostatic tolerance capacity before and after 20 days of bed rest in young subjects.     

Insufficient flow reduction during LBNP in both splanchnic and lower limb areas is associated with orthostatic intolerance after bedrest

We quantified the impact of a 60-day head-down tilt bed rest (HDBR) with countermeasures on the arterial response to supine lower body negative pressure (LBNP). Twenty-four women [8 control (Con), 8 exercise + LBNP (Ex-LBNP), and 8 nutrition (Nut) subjects] were studied during LBNP (0 to -45 mmHg) before (pre) and on HDBR day 55 (HDBR-55). Left ventricle diastolic volume (LVDV) and mass, flow velocities in the middle cerebral artery (MCA flow) and femoral artery (femoral flow), portal vein cross-sectional area (portal flow), and lower limb resistance (femoral resistance index) were measured. Muscle sympathetic nerve activity (MSNA) was measured in the fibular nerve. Subjects were identified as finishers or nonfinishers of the 10-min post-HDBR tilt test. At HDBR-55, LVDV, mass, and portal flow were decreased from pre-HDBR (P < 0.05) in the Con and Nut groups only. During LBNP at HDBR-55, femoral and portal flow decreased less, whereas leg MSNA increased similarly, compared with pre-HDBR in the Con, Nut, and NF groups; 11 of 13 nonfinishers showed smaller LBNP-induced reductions in both femoral and portal flow (less vasoconstriction), whereas 10 of 11 finishers maintained vasoconstriction in either one or both regions. The relative distribution of blood flow in the cerebral versus portal and femoral beds during LBNP [MCA flow/(femoral + portal flow)] increased or reduced < 15% from pre-HDBR in 10 of 11 finishers but decreased > 15% from pre-HDBR in 11 of 13 nonfinishers. Abnormal vasoconstriction in both the portal and femoral vascular areas was associated with orthostatic intolerance. The vascular deconditioning was partially prevented by Ex-LBNP.     

Cardiovascular adaptations following detraining

We have recently summarized our data concerning endurance exercise training and its effect on blood pressure regulation during lower body negative pressure (LBNP). We found that endurance trained (ET) subjects were less tolerant to LBNP than their untrained (UT) counterparts. This decreased tolerance to LBNP was linked to a fitness related adaptation in cardiac compliance, an attenuated cardiopulmonary reflex regulation of peripheral vasoconstriction and an attenuated aortic-cardiac reflex. More recently we have found that 15 days of bed rest deconditioning (a severe form of detraining) in UT subjects resulted in a more responsive aortic-cardiac reflex. In severe detraining investigations, spaceflight and bed rest deconditioning a reduction in total blood and plasma volume were the manifest physiological changes. Therefore, we postulate that the increased aortic-reflex responsiveness was a compensation for the blood and plasma volume losses associated with detraining. Subsequently, we hypothesized that a generalized reduction of the normal daily aerobic activities of a healthy, young adult population would produce a moderate reduction in total blood and plasma volume and an up-regulation of the reflex blood pressure regulatory mechanisms.     

Cerebral vasoreactivity during hypercapnia is reset by augmented sympathetic influence

Sympathetic nerve activity influences cerebral blood flow, but it is unknown whether augmented sympathetic nerve activity resets cerebral vasoreactivity to hypercapnia. This study tested the hypothesis that cerebral vasodilation during hypercapnia is restrained by lower-body negative pressure (LBNP)-stimulated sympathoexcitation. Cerebral hemodynamic responses were assessed in nine healthy volunteers [age 25 yr (SD 3)] during rebreathing-induced increases in partial pressure of end-tidal CO(2) (Pet(CO(2))) at rest and during LBNP. Cerebral hemodynamic responses were determined by changes in flow velocity of middle cerebral artery (MCAV) using transcranial Doppler sonography and in regional cerebral tissue oxygenation (ScO(2)) using near-infrared spectroscopy. Pet(CO(2)) values during rebreathing were similarly increased from 41.9 to 56.5 mmHg at rest and from 40.7 to 56.0 mmHg during LBNP of -15 Torr. However, the rates of increases in MCAV and in ScO(2) per unit increase in Pet(CO(2)) (i.e., the slopes of MCAV/Pet(CO(2)) and ScO(2)/Pet(CO(2))) were significantly (P ≤0.05) decreased from 2.62 ± 0.16 cm·s(-1)·mmHg(-1) and 0.89 ± 0.10%/mmHg at rest to 1.68 ± 0.18 cm·s(-1)·mmHg(-1) and 0.63 ± 0.07%/mmHg during LBNP. In conclusion, the sensitivity of cerebral vasoreactivity to hypercapnia, in terms of the rate of increases in MCAV and in ScO(2), is diminished by LBNP-stimulated sympathoexcitation.     

Effects of pericardial constraint and ventricular interaction on left ventricular hemodynamics in the unloaded heart

Pericardial constraint and ventricular interaction influence left ventricular (LV) performance when preload is high. However, it is unclear if these constraining forces modulate LV filling when the heart is unloaded, such as during upright posture, in humans. Fifty healthy individuals underwent right heart catheterization to measure pulmonary capillary wedge (PCWP) and right atrial pressure (RAP). To evaluate the effects of pericardial constraint on hemodynamics, transmural filling pressure (LVTMP) was defined as PCWP-RAP. Beat-to-beat blood pressure (BP) waveforms were recorded, and stroke volume (SV) was derived from the Modelflow method. After measurements at -30 mmHg lower body negative pressure (LBNP), which approximates the upright position, LBNP was released, and beat-to-beat measurements were performed for 15 heartbeats. At -30 mmHg LBNP, RAP and PCWP were significantly decreased. During the first six beats of LBNP release, heart rate (HR) was unchanged, while BP increased from the fourth beat. RAP increased faster than PCWP resulting in an acute decrease in LVTMP from the fourth beat. A corresponding drop in SV by 3% was observed with no change in pulse pressure. From the 7th to 15th beats, LVTMP and SV increased steadily, followed by a decreased HR due to the baroreflex. A decreased TMP, but not PCWP, caused a transient drop in SV with no changes in HR or pulse pressure during LBNP release. These results suggest that the pericardium constrains LV filling during LBNP release, enough to cause a small but significant drop of SV, even at low cardiac filling pressure in healthy humans.     

Cardiac atrophy after bed rest and spaceflight.

Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity of cardiac muscle under different loading conditions.     

WISE 2005: altered cerebrovascular autoregulation after 60 day head-down bed rest

We tested the hypothesis that 60 days of head-down bed rest (HDBR) would affect cerebrovascular autoregulation and that this change would be correlated with changes in tolerance to the upright posture. Twenty-four healthy women (32 +/- 4 yrs) participated in a 60-d bed rest study at the MEDES Clinic in Toulouse, France. End tidal CO2 (ETCO2), continuous blood pressure (BP), middle cerebral artery (MCA) velocity and time to presyncope (endpoint) were measured during an orthostatic tolerance test conducted before/after bed rest. Given the large range of change in tolerance even within assigned countermeasure groups, we separated subjects for this analysis on the basis of the change in endpoint (Delta endpoint) pre- to post-bed rest. Autoregulation and CO2 responsiveness were evaluated on a different day from a two-breath test with intermittent hypercapnic exposure. Autoregressive moving average (ARMA) modeled the two confounding inputs, BP and CO2, on cerebrovascular blood flow. The cerebrovascular resistance index (CVRi) was expected to decrease following a decrease in BP at the MCA to assist in maintenance of cerebral blood flow. Subjects with the smallest Delta endpoint after bed rest had a 78% increase in the gain of the BP --> CVRi response. Meanwhile, the groups with greater decline in orthostatic tolerance post-HDBR had no change in the gain of this response. ETCO2 was lower overall following HDBR, decreasing from 41.8 +/- 3.4 to 40.2 +/- 3.0 in supine rest, 37.9 +/- 3.4 to 33.3 +/- 4.0 in early tilt, and 29.5 +/- 4.4 to 27.1 +/- 5.1 at pre-syncope. There was however, higher MCA velocity at any ETCO2 for post- compared to pre-HDBR. In summary, changes in autoregulation were found only in those subjects who had the smallest change from pre- to post-HDBR orthostatic tolerance. The changes may assist in buffering changes in cerebral blood flow during orthostatic hypotension post-HDBR. The reduction in ETCO2 after bed rest might be due to a change in chemoreceptor response to blood CO2, but the cerebrovascular system seems to have completely compensated.     

Supine lower body negative pressure exercise during bed rest maintains upright exercise capacity.

Bed rest and spaceflight reduce exercise fitness. Supine lower body negative pressure (LBNP) treadmill exercise provides integrated cardiovascular and musculoskeletal stimulation similar to that imposed by upright exercise in Earth gravity. We hypothesized that 40 min of supine exercise per day in a LBNP chamber at 1.0-1.2 body wt (58 +/- 2 mmHg LBNP) maintains aerobic fitness and sprint speed during 15 days of 6 degrees head-down bed rest (simulated microgravity). Seven male subjects underwent two such bed-rest studies in random order: one as a control study (no exercise) and one with daily supine LBNP treadmill exercise. After controlled bed-rest, time to exhaustion during an upright treadmill exercise test decreased 10%, peak oxygen consumption during the test decreased 14%, and sprint speed decreased 16% (all P < 0.05). Supine LBNP exercise during bed rest maintained all the above variables at pre-bed-rest levels. Our findings support further evaluation of LBNP exercise as a countermeasure against long-term microgravity-induced deconditioning.     

Effect of 6-week endurance training on hemodynamic and neurohormonal responses to lower body negative pressure (LBNP) in healthy young men.

Endurance training is considered as a factor impairing orthostatic tolerance although an improvement and lack of effect have been also reported. The mechanisms of the changes and their relation to initial tolerance of orthostasis are not clear. In the present study, effect of moderate running training on hemodynamic and neurohormonal changes during LBNP, a laboratory test simulating orthostasis, was investigated in subjects with high (HT) and low (LT) tolerance of LBNP. Twenty four male, healthy subjects were submitted to graded LBNP (-15, -30 and -50 mmHg) before and after training. During each test heart rate (HR), stroke volume (SV) and blood pressure, plasma catecholamines, ACTH, adrenomedullin, atrial natriuretic peptide, and renin activity were determined. Basing on initial test, 13 subjects who withstood LBNP at -50 mmHg for 10 min were allocated into HT group and 11 subjects who earlier showed presyncopal symptoms to LT group. Training improved LBNP tolerance in six LT subjects. This was associated with attenuated rate of HR increase and SV decline (before training, at -30 mmHg deltaHR was 21 +/- 4 beats/min and deltaSV - -36+/- 8 ml while after training the respective values were 8 +/- 4 beats/min and -11+/- 6 ml). No differences in hemodynamic response were found in HT subjects and those from LT group whose LBNP tolerance was unchanged. In neither group training affected neurohormonal changes except inhibition of plasma ACTH rise in subjects with improvement of LBNP tolerance. It is concluded that some subjects with low orthostatic tolerance may benefit from moderate training due to improvement of cardiac function regulation.     

WISE-2005: tibial and gastrocnemius vein and calf tissue response to LBNP after a 60-day bed rest with and without countermeasures.

The objective of this study was to quantify by echography the changes in the intramuscular [gastrocnemius (Gast)] and nonintramuscular [posterior tibial (Tib)] calf veins cross-sectional area (CSA) and the superficial tissue thickness (STth) in response to lower body negative pressure (LBNP) after 60-day head-down bed rest (HDBR). Twenty-four healthy women (25-40 yr) were divided into three groups: control (Con), treadmill-LBNP and flywheel (Ex-Lb), nutrition (Nut; protein supplement). All underwent a LBNP (0 and -45 mmHg) before and on day 55 of HDBR. Subjects were identified as finisher (F) or nonfinisher (NF) of a 10-min tilt test after 60 days of HDBR. There were no differences in resting CSA of the Tib and Gast veins on HDBR day 55 compared with pre-HDBR for the Ex-Lb, Con and Nut, or the F groups; however, for NF both the Tib and Gast vein CSA at rest were significantly smaller after HDBR. At -45 mmHg LBNP, Tib and Gast CSAs were not significantly different from before HDBR in all groups (Ex-Lb, Con, Nut, F, NF). However, percent change in CSA of both veins from rest to -45 mmHg LBNP was significantly greater in the Con and Nut groups compared with Ex-Lb, and also NF compared with F. Similarly, the percent increase in STth on going from rest to -45 mmHg was higher after HDBR in the Con and Nut groups compared with Ex-Lb, as well as NF compared with F. These results showed that the Ex-Lb countermeasure minimized the bed rest effect on leg vein capacitance (CSA percent change) and STth increase during LBNP, whereas Nut had no effect and that higher leg vein and superficial tissue capacitance were associated with reduced orthostatic tolerance.     

Seven days of bed rest decrease insulin action on glucose uptake in leg and whole body

Impaired glucose tolerance develops in normal humans after short-term bed rest. To elucidate the mechanism, insulin action on whole body glucose uptake rate (WBGUR) and leg glucose uptake rate (LGUR) was measured by sequential euglycemic clamp technique combined with femoral arterial and venous cannulation at insulin concentrations of 10 +/- 1, 18 +/- 1, 37 +/- 2, and 360 +/- 15 microU/ml. Studies were performed before (C) and after (BR) 7 days of strict bed rest. WBGUR was significantly lower after bed rest than before (5.5 +/- 0.4 and 7.2 +/- 0.8 mg.min-1.kg-1, respectively) when insulin was 37 microU/ml. LGUR was even more markedly depressed by bed rest, being 0.6 +/- 0.1, 0.9 +/- 0.2, and 2.8 +/- 0.4 mg.min-1.kg leg-1 (BR) compared with 0.9 +/- 0.1, 1.7 +/- 0.4, and 5.9 +/- 0.5 mg.min-1.kg leg-1 (C) (P less than 0.05) at the three lower insulin concentrations. At these insulin concentrations also, lactate release and glucose oxidation and glycogen storage estimated by indirect calorimetry were lower in the leg after bed rest. At the highest insulin dose WBGUR was similar on BR and C days, while LGUR was lower after bed rest. In conclusion, 7 days of bed rest decrease whole body insulin action, a fact that is explained by decreased insulin action in inactive muscle.