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To understand the impact of physical deconditioning with head-down tilt bed rest (HDBR) on the malleability of sympathetic discharge patterns, we studied 1) baseline integrated muscle sympathetic nerve activity (MSNA; microneurography) from 13 female participants in the WISE-2005 60-day HDBR study (retrospective analysis), 2) integrated MSNA and multiunit action potential (AP) analysis in 13 male participants performed on data collected at baseline and during physiological stress imposed by end-inspiratory apnea in a new 60-day HDBR study, and 3) a repeatability study (control; n = 6, retrospective analysis, 4 wk between tests). Neither baseline integrated burst frequency nor incidence were altered with HDBR (both P > 0.35). However, baseline integrated burst latency increased in both HDBR studies (male: 1.35 ± 0.02 to 1.39 ± 0.02 s, P < 0.01; female: 1.23 ± 0.02 to 1.29 ± 0.02 s, P < 0.01), whereas controls exhibited no change across two visits (1.25 ± 0.02 to 1.25 ± 0.02 s, group-by-time interaction, P = 0.02). With the exception of increased AP latency ( P = 0.03), male baseline AP data did not change with HDBR (all P > 0.19). The change in AP frequency on going from baseline to apnea (∆94 ± 25 to ∆317 ± 55 AP/min, P < 0.01) and the number of active sympathetic clusters per burst (∆0 ± 0.2 to ∆1 ± 0.2 clusters/burst, P = 0.02) were greater post- compared with pre-HDBR. The change in total clusters with apnea was ∆0 ± 0.5 clusters pre- and ∆2 ± 0.7 clusters post-HDBR ( P = 0.07). These data indicate that 60-day HDBR modified discharge characteristics in baseline burst latency and sympathetic neural recruitment during apneic stress. NEW & NOTEWORTHY Long-duration bed rest did not modify baseline sympathetic burst frequency in male and female participants, but examination of additional features of the multiunit signal provided novel evidence to suggest augmented synaptic delays or processing times at baseline for all sympathetic action potentials. Furthermore, long-duration bed rest increased reflex-sympathetic arousal to apneic stress in male participants primarily by mechanisms involving an augmented firing rate of action potential clusters active at baseline.

Purpose: The objective of the study was to evaluate the effect of short-term, head-down bed rest (HDBR), with and without artificial gravity countermeasures, on splanchnic and lower limb vein properties., Methods: Data were collected from 12 men before and after 5 d of continuous -6° HDBR without countermeasures (CON) and with two artificial gravity countermeasure protocols: 30-min continuous centrifugation (AG1), and 30-min intermittent centrifugation (AG2). Portal (PV), tibial (TibV), and gastrocnemius (GastV) veins were investigated by echography supine and after 30 min of head-up tilt., Results: After HDBR, there was no change in PV, TibV, or GastV cross-sectional area at rest in any of the three conditions. In response to tilt, GastV and TibV area increased (168±141% and 192±124%, respectively) with no change in this response post-HDBR in any of the experimental conditions (P>0.05). PV area decreased with tilt (-33±13%) and was not different pre- to post-HDBR in the CON or AG1 conditions. However, there was a greater reduction in PV area in the AG2 group post-HDBR (-32±10% pre, -49±9% post-HDBR, P=0.003)., Conclusions: Calf veins were not significantly affected by 5 d of HDBR and did not appear to be negatively impacted by the artificial gravity countermeasures over this time period. In addition, the intermittent protocol resulted in better splanchnic vasoconstriction in response to head-up tilt, which may have contributed to a better maintenance of orthostatic tolerance post-HDBR.

This study tested the hypothesis that cardiovascular effects of sublingual nitroglycerin (NG) would be exaggerated after 56 days of 6° head-down bed rest (HDBR) in women, and that an aerobic and resistive exercise countermeasure (EX, n = 8) would reduce the effect compared with HDBR without exercise (CON, n = 7). Middle cerebral artery maximal blood flow velocity (CBFV), cardiac stroke volume (SV), and superficial femoral artery blood flow (Doppler ultrasound) were recorded at baseline rest and for 5 min following 0.3 mg sublingual NG. Post-HDBR, NG caused greater increases in heart rate (HR) in CON compared with EX (+24.9 ± 7.7 and +18.8 ± 6.6 beats/min, respectively, P < 0.0001). The increase in HR combined with reductions in SV to maintain cardiac output. Systolic, mean, and pulse pressures were reduced 5-10 mmHg by NG, but total peripheral resistance was only slightly reduced at 3 min after NG. Reductions in CBFV of -12.5 ± 3.8 cm/s were seen after NG, but a reduction in the Doppler resistance index suggested dilation of the middle cerebral artery with no differences after HDBR. The femoral artery dilated with NG and blood flow was reduced ∼50% with the appearance of large negative waves suggesting a marked increase in downstream resistance, but there were no effects of HDBR. In general, responses of women to NG were not altered by HDBR; the greater increase in HR in CON but not EX was probably a consequence of cardiovascular deconditioning. These results contrast with the hypothesis and a previous investigation of men after HDBR by revealing no change in cardiovascular responses to exogenous nitric oxide.

Mild lower-body negative pressure (LBNP) has been utilized to selectively unload cardiopulmonary baroreceptors, but there is evidence that arterial baroreceptors can be transiently unloaded after the onset of mild LBNP. In this paper, a black box mathematical model for the prediction of diastolic blood pressure (DBP) variability from multiple inputs (systolic blood pressure, R-R interval duration, and central venous pressure) was applied to interpret the dynamics of blood pressure maintenance under the challenge of LBNP and in long-duration, head-down bed rest (HDBR). Hemodynamic recordings from seven participants in the WISE (Women's International Space Simulation for Exploration) Study collected during an experiment of incremental LBNP (-10 mmHg, -20 mmHg, -30 mmHg) were analyzed before and on day 50 of a 60-day-long HDBR campaign. Autoregressive spectral analysis focused on low-frequency (LF, ~0.1 Hz) oscillations of DBP, which are related to fluctuations in vascular resistance due to sympathetic and baroreflex regulation of vasomotor tone. The arterial baroreflex-related component explained 49 ± 13% of LF variability of DBP in spontaneous conditions, and 89 ± 9% (P < 0.05) on day 50 of HDBR, while the cardiopulmonary baroreflex component explained 17 ± 9% and 12 ± 4%, respectively. The arterial baroreflex-related variability was significantly increased in bed rest also for LBNP equal to -20 and -30 mmHg. The proposed technique provided a model interpretation of the proportional effect of arterial baroreflex vs. cardiopulmonary baroreflex-mediated components of blood pressure control and showed that arterial baroreflex was the main player in the mediation of DBP variability. Data during bed rest suggested that cardiopulmonary baroreflex-related effects are blunted and that blood pressure maintenance in the presence of an orthostatic stimulus relies mostly on arterial control.

The objective of this study is to assess by echography and Doppler the Cerebral (Vmca), Aortic (Vao) and Femoral (Vfem) arterial flow velocity and calf vein (Tibial, Gastrocnemius) section (Tib, Gast) during orthostatic intolerance (OI) test after a 60-day, head down tilt bed rest (HDBR). Twenty-four women (25-40 years) underwent a 60-day HDBR at -6°: eight as control (Con), eight with exercise against lower body negative pressure (Ex-Lb) and eight with nutrition supplement (Nut). Before and after (R0) HDBR, all subjects underwent a 10-min, 80° tilt followed by progressive LBNP until presyncope. After the post-HDBR Tilt + LBNP test, two groups were identified: finishers (F, n = 11) who completed the Tilt and non-finishers (NF, n = 13). A higher percentage decrease in Vao flow, higher percentage distension of Tib vein and a lack of increase in Vmca/Vfem ratio during the post-HDBR Tilt + LBNP compared to pre-HDBR were correlated to OI, but not all of these abnormal responses were present in each of the NF subjects. Abnormal responses were more frequent in Con and Nut than in Ex-Lb subjects. (1) HDBR did not affect the cardiac, arterial and venous responses to the orthostatic test to the same extent in each subject. (2) Exercise within LBNP partially preserved the cardiovascular response to Tilt, while Nutrition supplementation had no efficacy. (3) Cerebral/femoral flow ratio and aortic flow were the parameters most closely related to OI. (4) Reduction in aortic flow was not the major hemodynamic change preceding syncope.

Unlabelled: We quantified the impact of 60-day head-down bed rest (HDBR) with countermeasures on arterial and venous response to tilt., Methods: Twenty-one males: 7 control (Con), 7 resistive vibration exercise (RVE) and 7 Chinese herb (Herb) were assessed. Subjects were identified as finisher (F) or non-finishers (NF) at the post-HDBR 20-min tilt test. The cerebral (MCA), femoral (FEM) arterial flow velocity and leg vascular resistance (FRI), the portal vein section (PV), the flow redistribution ratios (MCA/FEM; MCA/PV), the tibial (Tib), gastrocnemius (Gast), and saphenous (Saph) vein sections were measured by echography and Doppler ultrasonography. Arterial and venous parameters were measured at 3-min pre-tilt in the supine position, and at 1 min before the end of the tilt., Results: At post-HDBR tilt, MCA decreased more compared with pre-HDBR tilt in the Con, RVE, and Herb groups, the MCA/FEM tended to decrease in the Con and Herb groups (not significant) but remained stable in the RVE gr. FRI dropped in the Con gr, but remained stable in the Herb gr and increased in the RVE gr. PV decreased less in the Con and Herb groups but remained unchanged in the RVE gr. MCA/PV decreased in the Con and Herb groups, but increased to a similar extent in the RVE gr. Gast section significantly increased more in the Con gr only, whereas Tib section increased more in the Con and Herb groups but not in the RVE gr. The percent change in Saph section was similar at pre- and post-HDBR tilt., Conclusion: In the Con gr, vasoconstriction was reduced in leg and splanchnic areas. RVE and Herb contributed to prevent the loss of vasoconstriction in both areas, but the effect of RVE was higher. RVE and Herb contributed to limit Gast distension whereas only RVE had a protective effect on the Tib.

Whole body vibration with resistive exercise is a promising countermeasure against some weightlessness-induced dysfunctions. Our objective was to study whether the combination of low-magnitude whole body vibration with a resistive exercise can prevent the cardiovascular deconditioning induced by a nonstrict 60-day head-down bed rest (Earth Star International Bed Rest Experiment Project). Fourteen healthy men participated in this study. We recorded electrocardiograms and blood pressure waves by means of a noninvasive beat-by-beat measurement system (Cardiospace, integrated by Centre National d'Etudes Spatiales and Astronaut Center of China) during an orthostatic test (20 min of 75-degree head-up tilt test) before and immediately after bed rest. We estimated heart rate, blood pressure, cardiac output, stroke volume, total peripheral resistance, baroreflex sensitivity, and heart rate variability. Low-magnitude whole body vibration with resistive exercise prevented an increase of the sympathetic index (reflecting the sympathovagal balance of cardiac autonomic control) and limited the decrease of the spontaneous baroreflex sensitivity induced by 60 days of head-down bed rest. However, this countermeasure had very little effect on cardiac hemodynamics and did not improve the orthostatic tolerance. This combined countermeasure did not efficiently prevent orthostatic intolerance but prevents changes in the autonomic nervous system associated with cardiovascular deconditioning. The underlying mechanisms remain hypothetical but might involve cutaneous and muscular mechanoreceptors.

Objective: Check if the Temporal flow response to Tilt could provide early hemodynamic pattern in the minutes preceding a syncope during the Tilt test performed after a 60-d head down bedrest (HDBR)., Method: Twenty-one men divided into 3 groups [Control (Con), Resistive Vibration (RVE) and Chinese Herb (Herb)] underwent a 60 day HDBR. Pre and Post HDBR a 20 min Tilt identified Finishers (F) and Non Finishers (NF). Cerebral (MCA), Temporal (TEMP), Femoral (FEM) flow velocity, were measured by Doppler during the Tilt. Blood pressure (BP) was measured by arm cuff and cardiopress., Results and Discussion: Four of the 21 subjects were NF at the post HDBR Tilt test (Con gr:2, RVE gr: 1, Herb gr: 1). At 1 min and 10 s before end of Tilt in NF gr, FEM flow decreased less and MCA decreased more at post HDBR Tilt compared to pre (p<0.05), while in the F gr they changed similarly as pre. In NF gr: TEMP flow decreased more at post HDBR Tilt compared to pre, but only at 10 s before the end of Tilt (P<0.05). During the last 10 s a negative TEMP diastolic component appeared which induced a drop in mean velocity until Tilt arrest., Conclusion: The sudden drop in TEMP flow with onset of a negative diastolic flow preceding the decrease in MCA flow confirm that the TEMP vascular resistance respond more directly than the cerebral one to the cardiac output redistribution and that this response occur several seconds before syncope.

The objective of this study was to determine the accuracy of an echographic method for measuring the change in leg muscle volume against the gold standard, magnetic resonance imaging (MRI). Leg muscle volume was measured using an echographic scanner, which consisted of two metallic rails on which a probe holder moved via an electric engine. Ten to 20 transverse muscle views were collected along the area scanned, and the muscle cross-sectional area (CSA, cm2) was measured on each of them. The integration of all the CSAs along the scanned area provided the muscle volume (cm3). Echographic results were compared with MRI data on 24 subjects undergoing 60 d of bed rest (8 control "Con," 8 with exercise countermeasures "Ex" and 8 with nutrition countermeasures "Nut"). The vastus intermedius (VI) and the vastus medialis (VM) volumes decreased significantly and similarly in both Con and Nut (VI, -17%; VM, -21%; p < 0.02). In the Ex group, the VI and VM did not change significantly. The correlation coefficient between the muscle volume change measured with the echographic and MRI methods was 0.78. The present study confirms that the echographic scanner is sufficiently accurate for assessing muscle volume changes and detects the effect of exercise countermeasures on muscle volume during long-term bed rest.

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.

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.

This study tested the hypothesis that cardiovascular and hormonal responses to lower body negative pressure (LBNP) would be altered by 4-h head down bed rest (HDBR) in 11 healthy young men. In post-HDBR testing, three subjects failed to finish the protocol due to presyncopal symptoms, heart rate was increased during LBNP compared with pre-HDBR, mean arterial blood pressure was elevated at 0, -10, and -20 mmHg and reduced at -40 mmHg, central venous pressure (CVP) and cardiac stroke volume were reduced at all levels of LBNP. Plasma concentrations of renin, angiotensin II, and aldosterone were significantly lower after HDBR. Renin and angiotensin II increased in response to LBNP only post-HDBR. There was no effect of HDBR or LBNP on norepinephrine while epinephrine tended to increase at -40 mmHg post-HDBR (P = 0.07). Total blood volume was not significantly reduced. Splanchnic blood flow taken from ultrasound measurement of the portal vein was higher at each level of LBNP post-compared with pre-HDBR. The gain of the cardiopulmonary baroreflex relating changes in total peripheral resistance to CVP was increased after HDBR, but splanchnic vascular resistance was actually reduced. These results are consistent with our hypothesis and suggest that cardiovascular instability following only 4-h HDBR might be related to altered hormonal and/or neural control of regional vascular resistance. Impaired ability to distribute blood away from the splanchnic region was associated with reduced stroke volume, elevated heart rate, and the inability to protect mean arterial pressure.

We tested the hypotheses that women completing 56 days, 6 degrees head-down bed-rest (HDBR) would have changes in sensitivity of cardiovascular responses to adrenergic receptor stimulation and that frequent aerobic and resistive exercise would prevent these changes. Twenty-four women, eight controls, eight exercisers (lower body negative pressure treadmill and flywheel resistance exercise), and eight receiving nutritional supplement but no exercise were studied in baseline and during administration of the beta-agonist isoproterenol (ISO) and the alpha- and beta-agonist norepinephrine (NOR). In the control and nutrition groups, HDBR increased heart rate (HR) and reduced stroke volume (SV), and there was a significantly greater increase in HR with ISO after HDBR. In contrast, the HR and SV of the exercise group were unchanged from pre-HDBR. After HDBR, leg vascular resistance (LVR) was greater than pre-HDBR in the exercise group but reduced in control and nutrition. LVR was reduced with ISO and increased with NOR. Changes in total peripheral resistance were similar to those of LVR but of smaller magnitude, perhaps because changes in cerebrovascular resistance index were directionally opposite to those of LVR. There were no changes in sensitivity of the vascular resistance responses to adrenergic stimulation. The HR response might reflect a change in sensitivity or a necessary response to the reduction in SV after HDBR in control and nutrition groups. The reduced peripheral vascular resistance after HDBR might help to explain orthostatic intolerance in women. Exercise was an effective countermeasure to the HDBR effects.

This investigation set out to determine the effect of 56 days of head-down tilt bed rest (HDBR) and an exercise countermeasure on endothelial dependent and independent vascular function. 24women took part in this study. 8 subjects completed lower body resistance and aerobic exercise (EX, treadmill running 3-4 days per week for 40-min followed by 10-min of static LBNP, and resistive exercise on a flywheel device every 3rd day) and 16 subjects were considered as non-exercisers in a control group and a protein supplement group. FMD was induced by release of distal limb ischemia and NMD by sublingual administration of 0.3 mg of nitroglycerin before and after HDBR. Preliminary results of this study suggest that HDBR without EX results in a decreased resting diameter of the popliteal while EX increased the diameter. It is also suggested that FMD was elevated without exercise in both brachial and popliteal arteries, while pre-HDBR FMD was preserved by EX in the popliteal, but not the brachial artery. NMD appears to be elevated in the popliteal and femoral in the absence of exercise, but unchanged in the brachial artery or at any site for EX.

Unlabelled: The objective was to quantify calf vein cross section area (CSA) maximal enlargement and the percent change in response to LBNP (lower body negative pressure) after a 60 day bedrest., Method: The 24 healthy volunteers (25-40 y) of the WISE 60 day HDT(-6 degree) bedrest, were divided into 3 groups: Control (Co), Exercise countermeasure (Ex: treadmill under LBNP and flywheel), Nutrition (Nut: daily protein supplement). All were studied at -45mmHg LBNP pre and at HDT day 55. Posterior Tibial (Tib), and Gastrocnemian (Gast) vein were investigated by echography using an echographic probe fixed at the upper and posterior part of the calf. From the post HDT CSE test the subjects were identified as finisher or non finisher to the 10-min tilt tolerance test., Results: At LBNP-45mmHg, the maximal enlargement of the Tib and Gast veins remained constant pre, and at HDT day 55 in all group (Co, Ex, Nut, finisher, non finisher). For both veins there was a higher vein distension (percent change from supine rest to -45mmHg) in Co and Nut group compared to Ex group despite the maximal distension was similar in all groups. Also the vein distension was higher in non finisher than in finisher., Conclusion: The maximal distension of the vein were not affected nor by HDT nor by CM. The Ex counter-measure minimized the bed rest effect on leg vein distensibility (percent CSA change) while the Nut countermeasure had no effect. Higher leg vein distensibility was associated with reduced orthostatic tolerance.

Unlabelled: The objective was to quantify the Cerebral, and Femoral arterial hemodynamics as well as the calf vein section changes induced by a Tilt up test continuing with a Tilt plus LBNP after a 60 day HDT (WISE)., Method: 24 healthy volunteers (25-40 y) underwent a 60 day HDT (-6 degree) bedrest: 8 as Control (Co), 8 with Exercise (Ex: treadmill under LBNP and flywheel), 8 with Nutrition (Nut: daily protein supplement). At R+0 all of them underwent a 10 min 80 degree Tilt up test, to which several LBNP period of 3 min were added (from -10 to -50 mmHg by steps of 10 mmHg) until presyncopal stage. Cerebral and Femoral flow changes were assessed by Doppler. Posterior Tibial, and Gastrocnemian vein were investigated by echography., Results: At Post HDT 10 min Tilt: cerebral flow decreased similarly in the 3 groups, but more in the non finishers than in the finishers, while the femoral decreased similarly in all groups. Leg vascular resistance and cerebral/femoral flow ratio increased less in the Co and Nut gr than in the Ex gr, and also in the non finishers than in the finishers. Percent increase in Gastrocnemian and Tibial section was higher in Co and Nut gr than in Ex gr, and in non finishers than in finishers., Conclusion: Non exercise and non finisher subjects showed a lack of leg vasoconstriction, and a higher calf vein distensibility at post HDT Tilt test.

Twenty-four (24) healthy women from 25-40 years of age underwent orthostatic tolerance tests consisting of passive tilt and lower body negative pressure before and after completing 60-days of continuous -6 degree head down tilt bed rest (HDBR). Prior to HDBR, participants were assigned to one of three groups: control, exercise or nutrition. We aimed to identify any acute head up tilt changes in mean arterial pressure, pulse pressure, total peripheral resistance, cardiac output, stroke volume, or heart rate, which might predict tolerance or changes in tolerance with HDBR. Generally, these attempts were largely unsuccessful. The results indicate that the mechanisms of orthostatic failure are not strongly related to the way in which the body responds to the initial challenge. Additionally, the observation that some variables were predictive of tolerance before and not after tilt may indicate a change in the strategies used to maintain blood pressure, or differential adaptations to HDBR.

WISE-2005 studied 24 women during a 60-day head down bed rest (HDBR) who look part in an exercise countermeasure (LBNP-treadmill plus flywheel, EX) and no-exercise (No-EX). We conducted a series of experiments to explore changes in cardiovascular function and the ability of EX to prevent these changes. Resting arterial diameter in the arm was not affected but the leg arteries (femoral and popliteal) were significantly reduced in Np-EX, but was increased in EX. In this study we report on drug stimulated responses with sublingual nitroglycerin and infused isoproterenol. Heart rate increased in response to nitroglycerin with larger increases in No-EX after HDBR. Likewise during isoproterenol infusion the HR increase was greater after HDBR in the No-EX group. In all cases, the higher HR was associated with lower stroke volume in No-EX while stroke volume was protected in EX. These data do not support a change in sensitivity of beta-adrenergic receptors after HDBR. The leg vascular resistance decreased in response to isoproterenol and it decreased to a greater extent in No-EX than EX. These data were consistent with observations of lower leg vascular resistance during orthostatic challenge tests after HDBR. We conclude that consistent changes in cardiovascular function in the No-EX were detected by different methods that point to mechanisms contributing to orthostatic intolerance after HDBR.

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.

The objectives to determine both the contribution to orthostatic intolerance (OI) of calf venous volume during a stand-test, and the effects of a combined eccentric-concentric resistance exercise countermeasure on both vein response to orthostatic test and OI, after 90-day head-down tilt bed-rest (HDT). The subjects consisted of a control group (Co-gr, n = 9) and an exercise countermeasure group (CM-gr, n = 9). Calf volume and vein cross-sectional area (CSA) were assessed by plethysmography and echography during pre- and post-HDT stand-tests. From supine to standing (post-HDT), the tibial and gastrocnemius vein CSA increased significantly in intolerant subjects (tibial vein, +122% from pre-HDT; gastrocnemius veins, +145%; P < 0.05) whereas it did not in tolerant subjects. Intolerant subjects tended to have a higher increase in calf filling volume than tolerant subjects, in both sitting and standing positions. The countermeasure did not reduce OI. Absolute calf volume decreased similarly in both groups. Tibial and gastrocnemius vein CSA at rest did not change during HDT in either group. During the post-HDT stand-test, the calf filling volume increased more in the CM-gr than in the Co-gr both in the sitting (+1.3 +/- 5.1%, vs. -7.3 +/- 4.3%; P < 0.05) and the standing positions (+56.1 +/- 23.7% vs. +1.6 +/- 9.6%; P < 0.05). The volume ejected by the muscle venous pump increased only in the CM-gr (+38.3 +/- 21.8%). This study showed that intolerant subjects had a higher increase in vein CSA in the standing position and a tendency to present a higher calf filling volume in the sitting and standing positions. It also showed that a combined eccentric-concentric resistance exercise countermeasure had no effects on either post-HDT OI or on the venous parameters related to it.

Thigh cuffs, presently named "bracelets," consist of two straps fixed to the upper part of each thigh, applying a pressure of 30 mmHg. The objective was to evaluate the cardiac, arterial, and venous changes in a group of subjects in head-down tilt (HDT) for 7 days by using thigh cuffs during the daytime, and in a control group not using cuffs. The cardiovascular parameters were measured by echography and Doppler. Seven days in HDT reduced stroke volume in both groups (-10%; P < 0.05). Lower limb vascular resistance decreased more in the cuff group than in the control group (-29 vs. -4%; P < 0.05). Cerebral resistance increased in the control group only (+6%; P < 0.05). The jugular vein increased (+45%; P < 0.05) and femoral and popliteal veins decreased in cross-sectional area in both groups (-45 and -8%, respectively; P < 0.05). Carotid diameter tended to decrease (-5%; not significant) in both groups. Heart rate, blood pressure, cardiac output, and total resistance did not change significantly. After 8 h with thigh cuffs, the cardiac and arterial parameters had recovered their pre-HDT level except for blood pressure (+6%; P < 0.05). Jugular vein size decreased from the pre-HDT level (-21%; P < 0.05), and femoral and popliteal vein size increased (+110 and +136%, respectively; P < 0.05). The thigh cuffs had no effect on the development of orthostatic intolerance during the 7 days in HDT.