Skin surface cooling improves orthostatic tolerance following prolonged head-down bed rest

Prolonged exposure to microgravity, as well as its ground-based analog, head-down bed rest (HDBR), reduces orthostatic tolerance in humans. While skin surface cooling improves orthostatic tolerance, it remains unknown whether this could be an effective countermeasure to preserve orthostatic tolerance following HDBR. We therefore tested the hypothesis that skin surface cooling improves orthostatic tolerance after prolonged HDBR. Eight subjects (six men and two women) participated in the investigation. Orthostatic tolerance was determined using a progressive lower-body negative pressure (LBNP) tolerance test before HDBR during normothermic conditions and on day 16 or day 18 of 6° HDBR during normothermic and skin surface cooling conditions (randomized order post-HDBR). The thermal conditions were achieved by perfusing water (normothermia ～34°C and skin surface cooling ～12-15°C) through a tube-lined suit worn by each subject. Tolerance tests were performed after ～30 min of the respective thermal stimulus. A cumulative stress index (CSI; mmHg LBNP·min) was determined for each LBNP protocol by summing the product of the applied negative pressure and the duration of LBNP at each stage. HDBR reduced normothermic orthostatic tolerance as indexed by a reduction in the CSI from 1,037 ± 96 mmHg·min to 574 ± 63 mmHg·min (P < 0.05). After HDBR, skin surface cooling increased orthostatic tolerance (797 ± 77 mmHg·min) compared with normothermia (P < 0.05). While the reduction in orthostatic tolerance following prolonged HDBR was not completely reversed by acute skin surface cooling, the identified improvements may serve as an important and effective countermeasure for individuals exposed to microgravity, as well as immobilized and bed-stricken individuals.     

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.     

Pathophysiology of orthostatic hypotension after bed rest: paradoxical sympathetic withdrawal

Although orthostatic hypotension is a common clinical syndrome after spaceflight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR), the pathophysiology remains unclear. The authors' hypothesis that a decrease in sympathetic nerve activity is the major pathophysiology underlying orthostatic hypotension after HDBR was tested in a study involving 14-day HDBR in 22 healthy subjects who showed no orthostatic hypotension during 15-min 60 degrees head-up tilt test (HUT) at baseline. After HDBR, 10 of 22 subjects demonstrated orthostatic hypotension during 60 degrees HUT. In subjects with orthostatic hypotension, total activity of muscle sympathetic nerve activity (MSNA) increased less during the first minute of 60 degrees HUT after HDBR (314% of resting supine activity) than before HDBR (523% of resting supine activity, P < 0.05) despite HDBR-induced reduction in plasma volume (13% of plasma volume before HDBR). The postural increase in total MSNA continued during several more minutes of 60 degrees HUT while arterial pressure was maintained. Thereafter, however, total MSNA was paradoxically suppressed by 104% of the resting supine level at the last minute of HUT (P < 0.05 vs. earlier 60 degrees HUT periods). The suppression of total MSNA was accompanied by a 22 +/- 4-mmHg decrease in mean blood pressure (systolic blood pressure <80 mmHg). In contrast, orthostatic activation of total MSNA was preserved throughout 60 degrees HUT in subjects who did not develop orthostatic hypotension. These data support the hypothesis that a decrease in sympathetic nerve activity is the major pathophysiological factor underlying orthostatic hypotension after HDBR. It appears that the diminished sympathetic activity, in combination with other factors associated with HDBR (e.g., hypovolemia), may predispose some individuals to postural hypotension.     

Arterial baroreflex control of sympathetic vasoconstrictor traffic and orthostatic intolerance after head-down bed rest

The purpose of the present study is to examine the changes in the arterial baroreflex control of muscle sympathetic nerve activity (MSNA) after head-down bed rest (HDBR), in relation to orthostatic hypotension after HDBR. Therefore, we performed 60 degrees head-up tilt (HUT) tests before and after 14 days of HDBR, with monitoring MSNA, heart rate and blood pressure. We calculated the gain of the arterial baroreflex control of MSNA, and compared the gains between the subjects who did (defined as the fainters) and those who did not (defined as the nonfainters) become presyncopal in HUT tests after HDBR.     

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。     

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.     

Effect of head-down bed rest on the neuroendocrine response to orthostatic stress in physically fit men

The role of neuroendocrine responsiveness in the development of orthostatic intolerance after bed rest was studied in physically fit subjects. Head-down bed-rest (HDBR, -6 degrees, 4 days) was performed in 15 men after 6 weeks of aerobic training. The standing test was performed before, after training and on day 4 of the HDBR. Orthostatic intolerance was observed in one subject before and after training. The blood pressure response after training was enhanced (mean BP increments 18+/-2 vs. 13+/- 2 mm Hg, p<0.05, means +/- S.E.M.), although noradrenaline response was diminished (1.38+/-0.18 vs. 2.76+/-0.25 mol.l(-1), p<0.01). Orthostatic intolerance after HDBR was observed in 10 subjects, the BP response was blunted, and noradrenaline as well as plasma renin activity (PRA) responses were augmented (NA 3.10+/-0.33 mol.l(-1), p<0.001; PRA 2.98+/-1.12 vs. 0.85+/-0.15 ng.ml(-1), p<0.05). Plasma noradrenaline, adrenaline and aldosterone responses in orthostatic intolerant subjects were similar to the tolerant group. We conclude that six weeks of training attenuated the sympathetic response to standing and had no effect on the orthostatic tolerance. In orthostatic intolerance the BP response induced by subsequent HDBR was absent despite an enhanced sympathetic response.     

Baroreflex control of muscle sympathetic nerve activity after 120 days of 6 degrees head-down bed rest

To examine how long-lasting microgravity simulated by 6 degrees head-down bed rest (HDBR) induces changes in the baroreflex control of muscle sympathetic nerve activity (MSNA) at rest and changes in responses of MSNA to orthostasis, six healthy male volunteers (range 26-42 yr) participated in Valsalva maneuver and head-up tilt (HUT) tests before and after 120 days of HDBR. MSNA was measured directly using a microneurographic technique. After long-term HDBR, resting supine MSNA and heart rate were augmented. The baroreflex slopes for MSNA during Valsalva maneuver (in supine position) and during 60 degrees HUT test, determined by least-squares linear regression analysis, were significantly steeper after than before HDBR, whereas the baroreflex slopes for R-R interval were significantly flatter after HDBR. The increase in MSNA from supine to 60 degrees HUT was not different between before and after HDBR, but mean blood pressure decreased in 60 degrees HUT after HDBR. In conclusion, the baroreflex control of MSNA was augmented, whereas the same reflex control of R-R interval was attenuated after 120 days of HDBR.     

Effect of sleep restriction on orthostatic cardiovascular control in humans.

We hypothesized that sleep restriction (4 consecutive nights, 4 h sleep/night) attenuates orthostatic tolerance. The effect of sleep restriction on cardiovascular responses to simulated orthostasis, arterial baroreflex gain, and heart rate variability was evaluated in 10 healthy volunteers. Arterial baroreflex gain was determined from heart rate responses to nitroprusside-phenylephrine injections, and orthostatic tolerance was tested via lower body negative pressure (LBNP). A Finapres device measured finger arterial pressure. No difference in baroreflex function, heart rate variability, or LBNP tolerance was observed with sleep restriction (P > 0.3). Systolic pressure was greater at -60 mmHg LBNP after sleep restriction than before sleep restriction (110 +/- 6 and 124 +/- 3 mmHg before and after sleep restriction, respectively, P = 0.038), whereas heart rate decreased (108 +/- 8 and 99 +/- 8 beats/min before and after sleep restriction, respectively, P = 0.028). These data demonstrate that sleep restriction produces subtle changes in cardiovascular responses to simulated orthostasis, but these changes do not compromise orthostatic tolerance.     

WISE 2005: vascular responses to 60-day bed rest in women

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.     

Effects of 18 days of bed rest on leg and arm venous properties.

Venous function may be altered by bed rest deconditioning. Yet the contribution of altered venous compliance to the orthostatic intolerance observed after bed rest is uncertain. The purpose of this study was to assess the effect of 18 days of bed rest on leg and arm (respectively large and small change in gravitational gradients and use patterns) venous properties. We hypothesized that the magnitude of these venous changes would be related to orthostatic intolerance. Eleven healthy subjects (10 men, 1 woman) participated in the study. Before (pre) and after (post) 18 days of 6 degrees head-down tilt bed rest, strain gauge venous occlusion plethysmography was used to assess limb venous vascular characteristics. Leg venous compliance was significantly decreased after bed rest (pre: 0.048 +/- 0.007 ml x 100 ml(-1) x mmHg(-1), post: 0.033 +/- 0.007 ml x 100 ml(-1) x mmHg(-1); P < 0.01), whereas arm compliance did not change. Leg venous flow resistance increased significantly after bed rest (pre: 1.73 +/- 1.08 mmHg x ml(-1) x 100 ml x min, post: 3.10 +/- 1.00 mmHg x ml(-1) x 100 ml x min; P < 0.05). Maximal lower body negative pressure tolerance, which was expressed as cumulative stress index (pressure x time), decreased in all subjects after bed rest (pre: 932 mmHg x min, post: 747 mmHg x min). The decrease in orthostatic tolerance was not related to changes in leg venous compliance. In conclusion, this study demonstrates that after bed rest, leg venous compliance is reduced and leg venous outflow resistance is enhanced. However, these changes are not related to measures of orthostatic tolerance; therefore, alterations in venous compliance do not to play a major role in orthostatic intolerance after 18 days of head-down tilt bed rest.     

Effects of 14 days of head-down tilt bed rest on cutaneous vasoconstrictor responses in humans.

This study tested the hypothesis that head-down tilt bed rest (HDBR) reduces adrenergic and nonadrenergic cutaneous vasoconstrictor responsiveness. Additionally, an exercise countermeasure group was included to identify whether exercise during bed rest might counteract any vasoconstrictor deficits that arose during HDBR. Twenty-two subjects underwent 14 days of strict 6 degrees HDBR. Eight of these 22 subjects did not exercise during HDBR, while 14 of these subjects exercised on a supine cycle ergometer for 90 min a day at 75% of pre-bed rest heart rate maximum. To assess alpha-adrenergic vasoconstrictor responsiveness, intradermal microdialysis was used to locally administer norepinephrine (NE), while forearm skin blood flow (SkBF; laser-Doppler flowmetry) was monitored over microdialysis membranes. Nonlinear regression modeling was used to identify the effective drug concentration that caused 50% of the cutaneous vasoconstrictor response (EC(50)) and minimum values from the SkBF-NE dose-response curves. In addition, the effects of HDBR on nonadrenergic cutaneous vasoconstriction were assessed via the venoarteriolar response of the forearm and leg. HDBR did not alter EC(50) or the magnitude of cutaneous vasoconstriction to exogenous NE administration regardless of whether the subjects exercised during HDBR. Moreover, HDBR did not alter the forearm venoarteriolar response in either the control or exercise groups during HDBR. However, HDBR significantly reduced the magnitude of cutaneous vasoconstriction due to the venoarteriolar response in the leg, and this response was similarly reduced in the exercise group. These data suggest that HDBR does not alter cutaneous vasoconstrictor responses to exogenous NE administration, whereas cutaneous vasoconstriction of the leg due to the venoarteriolar response is reduced after HDBR. It remains unclear whether attenuated venoarteriolar responses in the lower limbs contribute to reduced orthostatic tolerance after bed rest and spaceflight.     

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.     

Femoral to cerebral arterial blood flow redistribution and femoral vein distension during orthostatic tests after 4 days in the head-down tilt position or confinement

The first objective of this study was to confirm that 4 days of head-down tilt (HDT) were sufficient to induce orthostatic intolerance, and to check if 4 days of physical confinement may also induce orthostatic intolerance. Evidence of orthostatic intolerance during tilt-up tests was obtained from blood pressure and clinical criteria. The second objective was to quantify the arterial and venous changes associated with orthostatic intolerance and to check whether abnormal responses to the tilt test and lower body negative pressure (LBNP) may occur in the absence of blood pressure or clinical signs of orthostatic intolerance. The cerebral and lower limb arterial blood flow and vascular resistance, the flow redistribution between these two areas, and the femoral vein distension were assessed during tilt-up and LBNP by ultrasound. Eight subjects were given 4 days of HDT and, 1 month later, 4 days of physical confinement. Tilt and LBNP test were performed pre- and post-HDT and confinement. Orthostatic intolerance was significantly more frequent after HDT (63%) than after confinement (25%, P<0.001). Cerebral haemodynamic responses to tilt-up and LBNP tests were similar pre- and post-HDT or confinement. Conversely, during both tilt and LBNP tests the femoral vascular resistances increased less (P<0.002), and the femoral blood flow reduced less (P<0.001) after HDT than before HDT or after confinement. The cerebral to femoral blood flow ratio increased less after HDT than before (P<0.002) but remained unchanged before and after confinement. This ratio was significantly more disturbed in the subjects who did not complete the tilt test. The femoral superficial vein was more distended during post-HDT LBNP than pre-HDT or after confinement (P<0.01). In conclusion, 4 days of HDT were enough to alter the lower limb arterial vasoconstriction and venous distensibility during tilt-up and LBNP, which reduced the flow redistribution in favour of the brain in all HDT subjects. Confinement did not alter significantly the haemodynamic responses to orthostatic tests. The cerebral to femoral blood flow ratio measured during LBNP was the best predictor of orthostatic intolerance. Accepted: 12 December 1997     

WISE-2005: adrenergic responses of women following 56-days, 6 degrees head-down bed rest with or without exercise countermeasures

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.     

Altered hormonal regulation and blood flow distribution with cardiovascular deconditioning after short-duration head down bed rest.

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.     

Impaired Orthostatic Response in Patients With Type 2 Diabetes Mellitus After 48 Hours of Bed Rest

ObjectiveTo compare the effect of bed rest on orthostatic responses of patients with type 2 diabetes mellitus and nondiabetic control subjects.MethodsSix patients with type 2 diabetes and 6 nondiabetic control subjects underwent 48 hours of bed rest and 48 hours of ambulatory activity in randomized order. A 10-minute tilt test was conducted before and after each period of hospitalization, and cardiovascular responses to 80° head-up tilt were analyzed with use of a 2-factorial (study group and bed rest condition) analysis of variance design. We hypothesized that patients with diabetes would experience more severe changes in orthostatic response after bed rest.ResultsNo significant differences in orthostatic responses were observed before bed rest between control subjects and patients with diabetes. After bed rest, control subjects had a greater (P = .01) increase in heart rate during tilt in comparison with before bed rest (before versus after bed rest, 9 ± 4 versus 24 ± 7 beats/min) and maintained their blood pressure during tilt. After bed rest, patients with diabetes did not have a compensatory increase in heart rate and had a greater (P = .02) decline in systolic blood pressure during tilt in comparison with before bed rest (before versus after bed rest, -7 ± 10 versus -21 ± 11 mm Hg). Their arm and leg skin vasomotor responses (laser Doppler flowmetry) during tilt were not altered after bed rest and were similar to those in control subjects before and after bed rest.ConclusionCardiac neuropathy in patients with type 2 diabetes may prevent a compensatory heart rate response after bed rest deconditioning and result in a more severe orthostatic response. A greater decrease in blood pressure with upright tilt is evident after a relatively short period of bed rest. (Endocr Pract. 2009;15:104-110)     

Heart rate variability during head down tilt and lower body negative pressure in the Russian Tschibis

The cardiovascular function in space seems to be normal. However, abnormalities of cardiovascular responses have been found during lower body negative pressure suction in space. The etiology of the cardiovascular deconditioning in space is still unknown. A previous study showed, that short periods of head down tilt (HDT-6 degrees) induce changes in the spectral pattern of heart rate variabilty (HRV) and an increase in the sympathethic activation caused by orthostatic stress. The aim of this study was to test following hypotheses: 1. The dynamic of heart rate variability is different in the head down tilt and supine positions. 2. The application of lower body negative pressure (LBNP) during head down tilt induces similar heart rate variability patterns like the standing position. 3. After short term head down tilt the cardiovascular response to lower body negative pressure stressor is altered.     

Menstrual cycle and sex affect hemodynamic responses to combined orthostatic and heat stress

Women have decreased orthostatic tolerance compared with men, and anecdotal evidence suggests women are more susceptible to orthostatic intolerance in warm environments. Because estrogen and progesterone affect numerous physiological variables that may alter orthostatic tolerance, the purpose of our study was to compare orthostatic tolerance across the menstrual cycle phases in women during combined orthostatic and heat stress and to compare these data with those of men. Eight normally menstruating women and eight males (22 +/- 4.0 and 23 +/- 3.5 yr, respectively) completed the protocol. Women were studied during their early follicular (EF), ovulatory (OV), and midluteal (ML) phases. Men were studied twice within 2-4 wk. Heart rate, cardiac output, blood pressure, core temperature (T(c)), and cutaneous vascular conductance (CVC) were measured during three head-up tilt tests, consisting of two tilts in the thermoneutral condition and one tilt after a 0.5 degrees C rise in T(c). There was no difference in orthostatic tolerance across the menstrual cycle phases, despite higher CVC in the ML phase after heating (EF, 42.3 +/- 4.8; OV, 40.1 +/- 3.7; ML, 57.5 +/- 4.5; P < 0.05). Orthostatic tolerance in the heat was greater in men than women (P < 0.05). These data suggest that although many physiological variables associated with blood pressure regulation fluctuate during the menstrual cycle, orthostatic tolerance in the heat remains unchanged. Additionally, our data support a clear sex difference in orthostatic tolerance and extend upon previous data to show that the sex difference in the heat is not attributable to fluctuating hormone profiles during the menstrual cycle.     

Role of splanchnic constriction in governing the hemodynamic responses to gravitational stress in conscious dogs

Octreotide is a somatostatin analog that constricts the splanchnic circulation, thereby improving orthostatic tolerance. We tested the hypotheses that octreotide improves orthostatic tolerance by 1)increasing cardiac filling (right atrial) pressure via reductions in vascular capacity; 2) by causing an upward (i.e., cranial) shift of the hydrostatic indifferent point; and 3) by increasing arterial pressure via a reduction in total vascular conductance. Studies were carried out in acepromazine-sedated, hexamethonium-treated atrioventricular-blocked conscious dogs lightly restrained in lateral recumbency. Beat-by-beat cardiac output was held constant via computer-controlled ventricular pacing at rest and during 30 s of 30° head-up tilt. Octreotide (1.5 μg/kg iv) raised right atrial pressure by 0.5 mmHg and raised mean arterial pressure by 11 mmHg by reducing total vascular conductance (all P < 0.05). Right atrial pressure fell by a similar amount in response to tilting before and after octreotide, thus there was no difference in location of the hydrostatic indifferent point. These data indicate that octreotide improves orthostatic tolerance by decreasing total vascular conductance and by increasing cardiac filling pressure via a reduction in unstressed vascular volume and not by eliciting a cranial shift of the location of the hydrostatic indifferent point.