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.     

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。     

Leg crossing improves orthostatic tolerance in healthy subjects: a placebo-controlled crossover study

Vasovagal syncope is the most common cause of transient loss of consciousness, and recurrent vasovagal fainting has a profound impact on quality of life. Physical countermaneuvers are applied as a means of tertiary prevention but have so far only proven useful at the onset of a faint. This placebo-controlled crossover study tested the hypothesis that leg crossing increases orthostatic tolerance. Nine na?ve healthy subjects [6 females, median age 25 yr (range 20-41 yr), mean body mass index 23 (SD 2)] were subjected to passive head-up tilt combined with a graded lower body negative pressure challenge (20, 40, and 60 mmHg) determining orthostatic tolerance thrice, in randomized order: 1) control, 2) with leg crossing, and 3) with oral placebo. Blood pressure (Finometer), heart rate, and changes in thoracic blood volume (impedance), stroke volume, and cardiac output (Modelflow) were followed during orthostatic stress. Primary outcome was time to presyncope (systolic blood pressure /=140 beats/min). With leg crossing, orthostatic tolerance increased from 26 +/- 2 to 34 +/- 2 min (placebo 23 +/- 3 min, P < 0.001). During leg crossing, mean arterial pressure (81 vs. 81 mmHg) and cardiac output (95 vs. 94% supine) remained unchanged; heart rate increase was lower (13 vs. 18 beats/min, P < 0.05); stroke volume was higher (79 vs. 74% supine, P < 0.05); and there was a trend toward lower thoracic impedance. Leg crossing increases orthostatic tolerance in healthy human subjects. As a measure of prevention, it is a worthwhile addition to the management of vasovagal syncope.     

Cardiovascular and hormonal changes with different angles of head-up tilt in men

The purpose of this study was to assess the endocrine status, thoracic impedance, blood concentration, and hemodynamic dose-responses using different angles of passive head-up tilt (HUT) ranging from 12 degrees to 70 degrees in the same subjects. Measurements were performed during 20 min supine position (pre-HUT), 30 min upright (HUT12, HUT30, HUT53, or HUT70), and 20 min supine (post-HUT); subjects 70 min in the supine position only (HUT0) served as resting controls. Norepinephrine increased above resting control values by 19, 44, 80, and 102%; epinephrine by 30, 41, 64, and 68%; aldosterone by 29, 62, 139, and 165%; plasma renin activity n. s., 41, 91, and 89%; vasopressin n.s., 27, 47, and 59%; thoracic bioimpedance n. s., 8, 13, and 16%; heart rate n. s., 5, 26, and 45%, and mean arterial pressure n. s., 5, 7, and 10%; at min 27 of HUT12, HUT30, HUT53, and HUT70, respectively. Pulse pressure decreased with HUT53 and HUT70 by 4 and 10%. Hematocrit increased by 0.2, 1.7, 6.3, and 7.2%, respectively. Blood density increased by 2.3 and 3.0 g/l, plasma density by 1.7 and 1.8 g/l with HUT53 and HUT70. After finishing HUT, heart rate fell to values which stayed below pre-HUT, and also below resting control levels for > or = 5 min ("post-orthostatic bradycardia") even after the lowest orthostatic load (HUT12). Thoracic impedance and arterial pressure remained increased after terminating HUT30, HUT53, and HUT70. In conclusion, passive orthostatic loading of different extent produces specific dose-responses of different magnitude in the endocrine system, blood composition, thoracic impedance, and hemodynamic variables. The heart rate is depressed even after HUT12, while arterial blood pressure and thoracic impedance exceed pre-stimulus levels after greater head-up tilt, indicating altered cardiovascular response after passive orthostasis.     

Phenotypical evidence for a gender difference in cardiac norepinephrine transporter function

Norepinephrine transporter (NET) function has a central role in the regulation of synaptic norepinephrine concentrations. Clinical observations in orthostatic intolerance patients suggest a gender difference in NET function. We compared the cardiovascular response to selective NET inhibition with reboxetine between 12 healthy men and 12 age-matched women. Finger blood pressure, brachial blood pressure, and heart rate were measured. The subjects underwent cardiovascular autonomic reflex testing and a graded head-up tilt test. In a separate study, we applied incremental concentrations of tyramine and isoproterenol through subcutaneous microdialysis catheters in eight men and in eight women. NET inhibition elicited a threefold greater increase in supine blood pressure in men than women (P < 0.05). The pressor response was driven by an increased cardiac output. The orthostatic heart rate increase during NET inhibition was greater in men than women (56 +/- 5 beats/min in men, 42 +/- 4 beats/min in women, P < 0.001). In contrast, NET inhibition resulted in a similar suppression in the cold pressor and handgrip response, low-frequency blood pressure oscillations, and venous norepinephrine in the supine position. Men and women were similarly sensitive to the lipolytic effect of isoproterenol and tyramine. We conclude that NET inhibition results in more pronounced changes in cardiac regulation in men than women. Our observations suggest that the NET contribution to cardiac norepinephrine turnover may be decreased in women. The gender difference in NET function may not be expressed in tissues that are less NET dependent than the heart.     

Effects of Individualized Centrifugation Training on Orthostatic Tolerance in Men and Women

AimsExposure to artificial gravity (AG) at different G loads and durations on human centrifuges has been shown to improve orthostatic tolerance in men. However, the effects on women and of an individual-specific AG training protocol on tolerance are not known.MethodsWe examined the effects of 90 minutes of AG vs. 90 minutes of supine rest on the orthostatic tolerance limit (OTL), using head up tilt and lower body negative pressure until presyncope of 7 men and 5 women. Subjects were placed in the centrifuge nacelle while instrumented and after one-hour they underwent either: 1) AG exposure (90 minutes) in supine position [protocol 1, artificial gravity exposure], or 2) lay supine on the centrifuge for 90 minutes in supine position without AG exposure [protocol 2, control]. The AG training protocol was individualized, by first determining each subject’s maximum tolerable G load, and then exposing them to 45 minutes of ramp training at sub-presyncopal levels.ResultsBoth sexes had improved OTL (14 minutes vs 11 minutes, p < 0.0019) following AG exposure. When cardiovascular (CV) variables at presyncope in the control test were compared with the CV variables at the same tilt-test time (isotime) during post-centrifuge, higher blood pressure, stroke volume and cardiac output and similar heart rates and peripheral resistance were found post-centrifuge.ConclusionsThese data suggest a better-maintained central circulating blood volume post-centrifugation across gender and provide an integrated insight into mechanisms of blood pressure regulation and the possible implementation of in-flight AG countermeasure profiles during spaceflights.     

Nitric oxide synthase inhibition does not affect regulation of muscle sympathetic nerve activity during head-up tilt

To test the hypothesis that systemic inhibition of nitric oxide (NO) synthase does not alter the regulation of sympathetic outflow during head-up tilt in humans, in eight healthy subjects NO synthase was blocked by intravenous infusion of NG-monomethyl-L-arginine (L-NMMA). Blood pressure, heart rate, cardiac output, total peripheral resistance (TPR), and muscle sympathetic nerve activity (MSNA) were recorded in the supine position and during 60 degrees head-up tilt. In the supine position, infusion of L-NMMA increased blood pressure, via increased TPR, and inhibited MSNA. However, the increase in MSNA evoked by head-up tilt during L-NMMA infusion (change in burst rate: 24 +/- 4 bursts/min; change in total activity: 209 +/- 36 U/min) was similar to that during head-up tilt without L-NMMA (change in burst rate: 23 +/- 4 bursts/min; change in total activity: 251 +/- 52 U/min, n = 6, all P > 0.05). Moreover, changes in TPR and heart rate during head-up tilt were virtually identical between the two conditions. These results suggest that systemic inhibition of NO synthase with L-NMMA does not affect the regulation of sympathetic outflow and vascular resistance during head-up tilt in humans.     

Effects of gender and hypovolemia on sympathetic neural responses to orthostatic stress

We tested the hypothesis that women have blunted sympathetic neural responses to orthostatic stress compared with men, which may be elicited under hypovolemic conditions. Muscle sympathetic nerve activity (MSNA) and hemodynamics were measured in eight healthy young women and seven men in supine position and during 6 min of 60 degrees head-up tilt (HUT) under normovolemic and hypovolemic conditions (randomly), with approximately 4-wk interval. Acute hypovolemia was produced by diuretic (furosemide) administration approximately 2 h before testing. Orthostatic tolerance was determined by progressive lower body negative pressure to presyncope. We found that furosemide produced an approximately 13% reduction in plasma volume, causing a similar increase in supine MSNA in men and women (mean +/- SD of 5 +/- 7 vs. 6 +/- 5 bursts/min; P = 0.895). MSNA increased during HUT and was greater in the hypovolemic than in the normovolemic condition (32 +/- 6 bursts/min in normovolemia vs. 44 +/- 15 bursts/min in hypovolemia in men, P = 0.055; 35 +/- 9 vs. 45 +/- 8 bursts/min in women, P < 0.001); these responses were not different between the genders (gender effect: P = 0.832 and 0.814 in normovolemia and hypovolemia, respectively). Total peripheral resistance increased proportionately with increases in MSNA during HUT; these responses were similar between the genders. However, systolic blood pressure was lower, whereas diastolic blood pressure was similar in women compared with men during HUT, which was associated with a smaller stroke volume or stroke index. Orthostatic tolerance was lower in women, especially under hypovolemic conditions. These results indicate that men and women have comparable sympathetic neural responses during orthostatic stress under normovolemic and hypovolemic conditions. The lower orthostatic tolerance in women is predominantly because of a smaller stroke volume, presumably due to less cardiac filling during orthostasis, especially under hypovolemic conditions, which may overwhelm the vasomotor reserve available for vasoconstriction or precipitate neurally mediated sympathetic withdrawal and syncope.     

Effects of body weight-supported treadmill training on heart rate variability and blood pressure variability in individuals with spinal cord injury.

Individuals with spinal cord injury are prone to cardiovascular dysfunction and an increased risk of cardiovascular disease. Body weight-supported treadmill training (BWSTT) may enhance ambulation in individuals with incomplete spinal cord injury; however, its effects on cardiovascular regulation have not been investigated. The purpose of this study was to examine the effects of 6-mo of BWSTT on the autonomic regulation of heart rate (HR) and blood pressure (BP) in individuals with incomplete tetraplegia. Eight individuals [age 27.6 yr (SD 5.2)] with spinal cord injury [C4-C5; American Spinal Injury Association B-C; 9.6 yr (SD 7.5) postinjury] participated. Ten-minute HR and finger arterial pressure (Finapres) recordings were collected during 1) supine rest and 2) an orthostatic stress (60 degrees head-up tilt) before and after 6 mo of BWSTT. Frequency domain measures of HR variability [low-frequency (LF) power, high-frequency (HF) power, and LF-to-HF ratio] and BP variability (systolic and diastolic LF power) were used as clinically valuable indexes of neurocardiac and neurovascular control, respectively. There was a significant reduction in HR [61.9 (SD 6.9) vs. 55.7 beats/min (SD 7.7); P=0.05] and LF-to-HF ratio [1.23 (SD 0.47) vs. 0.99 (SD 0.40); P < 0.05] after BWSTT. There was a significant reduction in LF systolic BP [183.1 (SD 46.8) vs. 158.4 mmHg2 (SD 45.2); P < 0.01] but no change in BP. There were no significant effects of training on HR variability or BP variability during 60 degrees head-up tilt. In conclusion, individuals with incomplete tetraplegia retain the ability to make positive changes in cardiovascular autonomic regulation with BWSTT without worsening orthostatic intolerance.     

Physiological responses of aged men to head-up tilt during heat exposure

The effects of age on cardiovascular and thermoregulatory responses to passive tilting were investigated using six old (61-73 yr) and 10 young (21-39 yr) unacclimatized men. Experiments were carried out at 26 degrees C and after exposure to 40 degrees C and 40% relative humidity for 105 min. Continuous measurements of esophageal (Tes) and mean skin (Tsk) temperatures and heart rate (HR) were recorded. Other variables studied included blood pressure (BP), forearm blood flow (FBF), and cardiac output (CO), which were measured at 4- to 5-min intervals. Measurements were made in the supine position and after 70 degrees head-up tilt for 15 min. Cardioacceleration during the tilt test was greater in the young men than in the old. Other cardiovascular responses of the old men to orthostatism were qualitatively similar to that of the young except for FBF and forearm vascular conductance. The old men did not show significant changes in FBF during tilting, suggesting a deterioration in the sympathetic nervous reflex in the aged. However, other circulatory adaptations seemed to overcome this deficiency resulting in orthostatic tolerance similar to that of the young. During head-up tilt at 26 and 40 degrees C, Tes of both age groups increased. This may reflect a decrease in conductive heat transfer presumably due to diminished blood flow to the periphery.     

Coagulation Changes during Presyncope and Recovery

Orthostatic stress activates the coagulation system. The extent of coagulation activation with full orthostatic load leading to presyncope is unknown. We examined in 7 healthy males whether presyncope, using a combination of head up tilt (HUT) and lower body negative pressure (LBNP), leads to coagulation changes as well as in the return to baseline during recovery. Coagulation responses (whole blood thrombelastometry, whole blood platelet aggregation, endogenous thrombin potential, markers of endothelial activation and thrombin generation), blood cell counts and plasma mass density (for volume changes) were measured before, during, and 20 min after the orthostatic stress. Maximum orthostatic load led to a 25% plasma volume loss. Blood cell counts, prothrombin levels, thrombin peak, endogenous thrombin potential, and tissue factor pathway inhibitor levels increased during the protocol, commensurable with hemoconcentration. The markers of endothelial activation (tissue factor, tissue plasminogen activator), and thrombin generation (F1+2, prothrombin fragments 1 and 2, and TAT, thrombin-antithrombin complex) increased to an extent far beyond the hemoconcentration effect. During recovery, the markers of endothelial activation returned to initial supine values, but F1+2 and TAT remained elevated, suggestive of increased coagulability. Our findings of increased coagulability at 20 min of recovery from presyncope may have greater clinical significance than short-term procoagulant changes observed during standing. While our experiments were conducted in healthy subjects, the observed hypercoagulability during graded orthostatic challenge, at presyncope and in recovery may be an important risk factor particularly for patients already at high risk for thromboembolic events (e.g. those with coronary heart disease, atherosclerosis or hypertensives).     

Reduced orthostatic tolerance following 4 h head-down tilt

The cardiovascular responses to a 10-min 1.22 rad (70 degrees) head-up tilt orthostatic tolerance test (OST) was observed in eight healthy men following each of a 5-min supine baseline (control), 4 h of 0.1 rad (6 degrees) head-down tilt (HDT), or 4 h 0.52 rad (30 degrees) head-up tilt (HUT). An important clinical observation was presyncopal symptoms in six of eight subjects following 4 h HDT, but in no subjects following 4 h HUT. Immediately prior to the OST, there were no differences in heart rate, stroke volume, cardiac output, mean arterial pressure and total peripheral resistance for HDT and HUT. However, stroke volume and cardiac output were greater for the control group. Mean arterial pressure for the control group was less than HDT but not HUT. Over the full 10-min period of OST, the mean arterial pressure was not different between groups. Heart rate increased to the same level for all three treatments. Stroke volume decreased across the full time period for control and HDT, but only at 3 and 9 min for HUT. There was a higher total peripheral resistance in the HDT group than control or HUT. The pre-ejection period to left ventricular ejection time ratio was less in HDT than for control or HUT groups. These data indicate a rapid adaptation of the cardiovascular system to 4 h HDT that appears to be inappropriate on reapplication of a head to foot gravity vector. We speculate that the cause of the impaired orthostatic tolerance is decreased tone in venous capacitance vessels so that venous return is inadequate.     

Effect of hydration on some orthostatic and haematological responses to head-up tilt

Experiments were undertaken to determine the effects of hydration status on a) orthostatic responses, and on b), relative changes in intravascular volume and protein content, during 70 degrees head-up tilt (HUT). Six men underwent 45 min of HUT, preceded by 45 min supine, first dehydrated, and again 105 min later after rehydration with water. Heart rate was consistently lower following rehydration (p less than 0.01), while supine diastolic pressure was higher (p less than 0.02). Systolic pressure fell during dehydrated HUT (p less than 0.01), but not during rehydrated HUT. Postural haemoconcentration, which was reduced after rehydration (p less than 0.001), was accompanied by a decrease in intravascular albumin content (p less than 0.05). Two subjects experienced severe presyncopal symptoms during dehydrated HUT, but not during rehydrated HUT. Thus, it appears that rehydration after fluid restriction improves orthostatic tolerance. Furthermore, extravascular hydration status may be more important than intravascular hydration status in determining orthostatic tolerance.     

Cardiovascular response to functional electrical stimulation and dynamic tilt table therapy to improve orthostatic tolerance

Orthostatic hypotension is a common condition for individuals with stroke or spinal cord injury. The inability to regulate the central nervous system will result in pooling of blood in the lower extremities leading to orthostatic intolerance. This study compared the use of functional electrical stimulation (FES) and passive leg movements to improve orthostatic tolerance during head-up tilt. Four trial conditions were assessed during head-up tilt: (1) rest, (2) isometric FES of the hamstring, gastrocnemius and quadriceps muscle group, (3) passive mobilization using the Erigo dynamic tilt table; and (4) dynamic FES (combined 2 and 3). Ten healthy male subjects experienced 70 degrees head-up tilt for 15 min under each trial condition. Heart rate, blood pressure and abdominal echograms of the inferior vena cava were recorded for each trial. Passive mobilization and dynamic FES resulted in an increase in intravascular blood volume, while isometric FES only resulted in elevating heart rate. No significant differences in blood pressure were observed under each condition. We conclude that FES combined with passive stepping movements may be an effective modality to increase circulating blood volume and thereby tolerance to postural hypotension in healthy subjects.     

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.     

Vascular perturbations in the chronic orthostatic intolerance of the postural orthostatic tachycardia syndrome.

Chronic orthostatic intolerance is often related to the postural orthostatic tachycardia syndrome (POTS). POTS is characterized by upright tachycardia. Understanding of its pathophysiology remains incomplete, but edema and acrocyanosis of the lower extremities occur frequently. To determine how arterial and venous vascular properties account for these findings, we compared 13 patients aged 13-18 yr with 10 normal controls. Heart rate and blood pressure were continuously recorded, and strain-gauge plethysmography was used to measure forearm and calf blood flow, venous compliance, and microvascular filtration while the subject was supine and to measure calf blood flow and calf size change during head-up tilt. Resting venous pressure was higher in POTS compared with control (16 vs. 10 mmHg), which gave the appearance of decreased compliance in these patients. The threshold for edema formation decreased in POTS patients compared with controls (8.3 vs. 16.3 mmHg). With tilt, early calf blood flow increased in POTS patients (from 3.4 +/- 0.9 to 12.6 +/- 2.3 ml. 100 ml(-1). min(-1)) but did not increase in controls. Calf volume increased twice as much in POTS patients compared with controls over a shorter time of orthostasis. The data suggest that resting venous pressure is higher and the threshold for edema is lower in POTS patients compared with controls. Such findings make the POTS patients particularly vulnerable for edema fluid collection. This may signify a redistribution of blood to the lower extremities even while supine, accounting for tachycardia through vagal withdrawal.     

Gender affects sympathetic neurovascular control during postural stress

Sympathetic outflow increases during head-up tilt (HUT) to stabilize blood pressure in the presence of decreases in venous return and stroke volume (SV). Otherwise, orthostatic hypotension would develop. Gender differences in orthostatic tolerance have been noted but the mechanisms are still uncertain. More recently, Waters et al. reported in a limited sample, greater susceptibility of women to demonstrate orthostatic intolerance following space flight. Therefore, it is important to understand gender differences in reflex blood pressure regulation. Recently, we reported smaller increments in muscle sympathetic nerve activity (MSNA) in healthy women during graded HUT and a non-baroreflex cold pressor test. The purpose of this report is to examine the hypothesis that gender differences in blood pressure control during HUT are related to important variations in MSNA discharge patterns.     

Effect of acute exposure to 3660 m altitude on orthostatic responses and tolerance.

Orthostatic reflexes were examined at 375 m and after 60 min of exposure in a hypobaric chamber at 3660 m using a 20-min 70 degrees head-up tilt (HUT) test. Mean arterial blood pressure, R wave-R wave interval (RRI), and mean cerebral blood flow velocity (MFV) were examined with coarse-graining spectral analysis. Of 14 subjects, 7 at 375 m and 12 at 3660 m were presyncopal. Immediately on arrival to high altitude, breathing frequency and MFV increased, and endtidal PCO2, RRI, RRI complexity, and the parasympathetic nervous system indicator decreased. MFV was similar in HUT at both altitudes. The sympathetic nervous system indicator increased with tilt at 3660 m, whereas parasympathetic nervous system indicator decreased with tilt at both altitudes. Multiple regression analysis of supine variables from either 375 or 3660 m and the time to presyncope at 3660 m indicated that, after 1 h of exposure, increased presyncope at altitude was the result of 1). ineffective peripheral vasoconstriction, despite increased cardiac sympathetic nervous system activity with HUT, and 2). insufficient cerebral perfusion owing to cerebral vasoconstriction as the result of hypoxic hyperventilation-induced hypocapnia.     

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.     

The effect of time-of-day and sympathetic α1-blockade on orthostatic tolerance

Tolerance time to a standardized orthostatic stressor is markedly reduced in normotensive individuals in the morning. However, the physiological mechanisms that underpin this phenomenon are unknown. The purpose of this study was to examine the role of α(1)-adrenergic activity on orthostatic tolerance and associated cardiorespiratory and cerebrovascular responses, and to determine whether its endogenous modulation is important in the diurnal variation of orthostatic tolerance. In a four-trial, randomized placebo-controlled crossover experiment, 12 normotensive volunteers (aged 25 ± 1 yrs; mean ± SE) completed a 60° head-upward tilt (HUT; 15 min or until onset of presyncope) at 06:00 and 16:00 h, 90 min after the administration of either α(1)-blockade (prazosin, 1 mg/20 kg body weight) or placebo. Continuous beat-to-beat measurements of middle cerebral blood flow velocity (transcranial Doppler), blood pressure (Finometer), heart rate, stroke volume, cardiac output, and end-tidal carbon dioxide were obtained. Independent of time-of-day, α(1)-blockade markedly reduced the ability to tolerate a 15-min 60° HUT; tolerance time was 229% shorter compared with the placebo condition (p ≤ .0001). Moreover, a marked diurnal variation in orthostatic tolerance was evident following α(1)-adrenergic blockade; e.g., tolerance time in the morning (176 ± 30 s) was lower than in the afternoon (354 ± 75 s; p =?.04). These findings highlight an important role of α(1)-sympathetic vasoconstrictor activity in acutely regulating blood pressure and offsetting syncope, especially in the early morning.