Leg vasoconstriction during head-up tilt in patients with autonomic failure is not abolished

Maintaining blood pressure during orthostatic challenges is primarily achieved by baroreceptor-mediated activation of the sympathetic nervous system, which can be divided into preganglionic and postganglionic parts. Despite their preganglionic autonomic failure, spinal cord-injured individuals demonstrate a preserved peripheral vasoconstriction during orthostatic challenges. Whether this also applies to patients with postganglionic autonomic failure is unknown. Therefore, we assessed leg vasoconstriction during 60° head-up tilt in five patients with pure autonomic failure (PAF) and two patients with autonomic failure due to dopamine-β-hydroxylase (DBH) deficiency. Ten healthy subjects served as controls. Leg blood flow was measured using duplex ultrasound in the right superficial femoral artery. Leg vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow. DBH-deficient patients were tested off and on the norepinephrine pro-drug l-threo-dihydroxyphenylserine (l-DOPS). During 60° head-up tilt, leg vascular resistance increased significantly in PAF patients [0.40 ± 0.38 (+30%) mmHg·ml(-1)·min(-1)]. The increase in leg vascular resistance was not significantly different from controls [0.88 ± 1.04 (+72%) mmHg·ml(-1)·min(-1)]. In DBH-deficient patients, leg vascular resistance increased by 0.49 ± 0.01 (+153%) and 1.52 ± 1.47 (+234%) mmHg·ml(-1)·min(-1) off and on l-DOPS, respectively. Despite the increase in leg vascular resistance, orthostatic hypotension was present in PAF and DBH-deficient patients. Our results demonstrate that leg vasoconstriction during orthostatic challenges in patients with PAF or DBH deficiency is not abolished. This indicates that the sympathetic nervous system is not the sole or pivotal mechanism inducing leg vasoconstriction during orthostatic challenges. Additional vasoconstrictor mechanisms may compensate for the loss in sympathetic nervous system control.     

Reflex vascular defects in the orthostatic tachycardia syndrome of adolescents.

Dependent pooling occurs in postural orthostatic tachycardia syndrome (POTS) related to defective vasoconstriction. Increased venous pressure (Pv) >20 mmHg occurs in some patients (high Pv) but not others (normal Pv). We compared 22 patients, aged 12-18 yr, with 13 normal controls. Continuous blood pressure and strain-gauge plethysmography were used to measure supine forearm and calf blood flow, resistance, venous compliance, and microvascular filtration, and blood flow and swelling during 70 degrees head-up tilt. Supine, high Pv had normal resistance in arms (26 +/- 2 mmHg x ml(-1) x 100 ml x min) and legs (34 +/- 3 mmHg x ml(-1) x 100 ml x min) but low leg blood flow (1.5 +/- 0.4 ml x 100 ml(-1) x min(-1)). Supine leg Pv (30 +/- 2 vs. 13 +/- 1 mmHg in control) exceeded the threshold for edema (isovolumetric pressure = 19 +/- 3 mmHg). Supine, normal Pv had high blood flow in arms (4.1 +/- 0.2 vs. 3.5 +/- 0.2 ml x 100 ml(-1) x min(-1) in control) and legs (3.8 +/- 0.4 vs. 2.7 +/- 0.3 ml x 100 ml(-1) x min(-1) in control) with low resistance. With tilt, calf blood flow increased steadily in POTS with high Pv and transiently increased in normal Pv. Calf volume increased in all POTS patients. Arm blood flow increased in normal Pv only with forearm maintained at heart level. These data suggest that there are (at least) two subgroups of POTS characterized by high Pv and low flow or normal Pv and high flow. These may correspond to abnormalities in local or baroreceptor-mediated vasoconstriction, respectively.     

Venous hydrostatic indifference point as a marker of postnatal adaptation to orthostasis in swine.

The postulate that venous adaptation assists postural baroreflex regulation by shifting the hydrostatic indifference point (HIP) toward the heart was investigated in eight midazolam-sedated newborn piglets. Whole body head-up (+15, +30, and +45 degrees ) and head-down (-15 and -30 degrees ) tilt provided a physiological range of orthostatic strain. HIP for all positive tilts shifted toward the heart (P < 0.05), +45 degrees HIP shifted most [6.7 +/- 0.3, 5.9 +/- 0.5, and 3.6 +/- 0.3 (SE) cm caudal to right atrium on days 1, 3, and 6, respectively]. HIP for negative tilts (3.0 +/- 0.2 cm caudal to right atrium) did not shift with postnatal age. Euthanasia on day 6 caused 2.1 +/- 0.3-cm caudal displacement of HIP for positive and negative tilts (P < 0.05). HIP proximity to right atrium was not altered by alpha-, beta-adrenoceptor and cholinoceptor blockade on day 5. It is concluded that early HIP migration reflects enhancement of venous pressure control to head-up orthostatic strain. The effect is independent of baroreflex-mediated adrenoceptor and cholinoceptor mechanisms.     

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.     

Myogenic origin of the hypotension induced by rapid changes in posture in awake dogs following autonomic blockade

The "push-pull" effect denotes the reduced tolerance to +G(z) (hypergravity) when +G(z) stress is preceded by exposure to hypogravity, i.e., fractional, zero, or negative G(z). The purpose of this study was to test the hypothesis that an exaggerated, myogenically mediated rise in leg vascular conductance contributes to the push-pull effect, using heart level arterial blood pressure as a measure of G tolerance. The approach was to impose control (30 s of 30 degrees head-up tilt) and push-pull (30 s of 30 degrees head-up tilt immediately preceded by 10 s of -15 degrees head-down tilt) gravitational stress after administration of hexamethonium (5 mg/kg) to inhibit autonomic ganglionic neurotransmission in seven dogs. Cardiac output or thigh level arterial pressure (myogenic stimulus) was maintained constant by computer-controlled ventricular pacing. The animals were sedated with acepromazine and lightly restrained in lateral recumbency on a tilt table. Following the onset of head-up tilt, the magnitude of the fall in heart level arterial pressure from baseline was -11.6 +/- 2.9 and -17.1 +/- 2.2 mmHg for the control and push-pull trials, respectively (P < 0.05), when cardiac output was maintained constant. Over 40% of the exaggerated fall in heart level arterial pressure was attributable to an exaggerated rise in hindlimb vascular conductance (P < 0.05). Maintaining thigh level arterial pressure constant abolished the exaggerated rise in hindlimb blood flow. Thus a push-pull effect largely attributable to a myogenically induced rise in leg vascular conductance occurs when autonomic function is inhibited.     

Lower vascular tone and larger plasma volume in Parkinson's disease with orthostatic hypotension

The pathophysiology of orthostatic hypotension in Parkinson's disease (PD) is incompletely understood. The primary focus has thus far been on failure of the baroreflex, a central mediated vasoconstrictor mechanism. Here, we test the role of two other possible factors: 1) a reduced peripheral vasoconstriction (which may contribute because PD includes a generalized sympathetic denervation); and 2) an inadequate plasma volume (which may explain why plasma volume expansion can manage orthostatic hypotension in PD). We included 11 PD patients with orthostatic hypotension (PD + OH), 14 PD patients without orthostatic hypotension (PD - OH), and 15 age-matched healthy controls. Leg blood flow was examined using duplex ultrasound during 60° head-up tilt. Leg vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow. In a subset of 9 PD + OH, 9 PD - OH, and 8 controls, plasma volume was determined by indicator dilution method with radiolabeled albumin ((125)I-HSA). The basal leg vascular resistance was significantly lower in PD + OH (0.7 ± 0.3 mmHg·ml(-1)·min) compared with PD - OH (1.3 ± 0.6 mmHg·ml(-1)·min, P < 0.01) and controls (1.3 ± 0.5 mmHg·ml(-1)·min, P < 0.01). Leg vascular resistance increased significantly during 60° head-up tilt with no significant difference between the groups. Plasma volume was significantly larger in PD + OH (3,869 ± 265 ml) compared with PD - OH (3,123 ± 377 ml, P < 0.01) and controls (3,204 ± 537 ml, P < 0.01). These results indicate that PD + OH have a lower basal leg vascular resistance in combination with a larger plasma volume compared with PD - OH and controls. Despite the increase in leg vascular resistance during 60° head-up tilt, PD + OH are unable to maintain their blood pressure.     

Regional difference of blood flow in anesthetized rats during reduced gravity induced by parabolic flight.

To examine a hypothesis that change in regional blood flow due to decreased hydrostatic pressure gradient and redistribution of blood during reduced gravity (rG) is different between organs, changes in cerebrocortical blood flow (CBF) and blood flow in the temporal muscle (MBF) with exposure to rG were measured in anesthetized rats in head-up tilt and flat positions during parabolic flight. Carotid arterial pressure (CAP), jugular venous pressure (JVP), and abdominal aortic pressure were also measured simultaneously. In the head-up tilt group, CBF increased by 15 +/- 3% within 3 s of entry into rG and rapidly recovered during rG. MBF also increased, but the change was significantly greater than that of CBF. JVP increased by 1.8 +/- 0.5 mmHg, probably due to loss of hydrostatic pressure gradient, since the measuring point of JVP was 2-3 cm above the hydrostatic indifference point. CAP and abdominal aortic pressure increased by 16.7 +/- 2 and 7.7 +/- 2 mmHg, respectively, compared with the 1-G condition. Muscle vascular resistance [(CAP-JVP)/MBF] decreased on entry into rG, but no significant change was observed in cerebrocortical vascular resistance [(CAP-JVP)/CBF]. In the flat group, no significant change was observed in all the variables. The results indicate that arteriolar vasodilatation occurs in the temporal muscle but not in the cerebral cortex. Thus the blood flow control mechanism at the onset of rG is different between intra- and extracranial organs.     

Hemodynamic consequences of rapid changes in posture in humans.

Tolerance to +G(z) gravitational stress is reduced when +G(z) stress is preceded by exposure to hypogravity (fraction, 0, or negative G(z)). For example, there is an exaggerated fall in eye-level arterial pressure (ELAP) early on during +G(z) stress (head-up tilt; HUT) when this stress is immediately preceded by -G(z) stress (head-down tilt; HDT). The aims of the present study were to characterize the hemodynamic consequences of brief HDT on subsequent HUT and to test the hypothesis that an elevation in leg vascular conductance induced by -G(z) stress contributes to the exaggerated fall in ELAP. Young healthy subjects (n = 3 men and 4 women) were subjected to 30 s of 30 degrees HUT from a horizontal position and to 30 s of 30 degrees HUT when HUT was immediately preceded by 20 s of -15 degrees HDT. Four bouts of HDT-HUT were alternated between five bouts of HUT in a counterbalanced designed to minimize possible time effects of repeated exposure to gravitational stress. One minute was allowed for recovery between tilts. Brief exposure to HDT elicited an exaggerated fall in ELAP during the first seconds of the subsequent HUT (-17.9 +/- 1.4 mmHg) compared with HUT alone (-12.4 +/- 1.2 mmHg, P <0.05) despite a greater rise in stroke volume (Doppler ultrasound) and cardiac output over this brief time period in the HDT-HUT trials compared with the HUT trials (thereafter stroke volume fell under both conditions). The greater fall in ELAP was associated with an exaggerated increase in leg blood flow (femoral artery Doppler ultrasound) and was therefore largely (70%) attributable to an exaggerated rise in estimated leg vascular conductance, confirming our hypotheses. Thus brief exposure to -G(z) stress leads to an exaggerated fall in ELAP during subsequent HUT, owing to an exaggerated increase in estimated leg vascular conductance.     

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.     

Effect of lower-body positive pressure on postural fluid shifts in men

To quantify the effect of 60 mm Hg lower-body positive pressure (LBPP) on orthostatic blood-volume shifts, the mass densities (+/- 0.1 g.1-1) of antecubital venous blood and plasma were measured in five men (27-42 years) during combined tilt table/antigravity suit inflation and deflation experiments. The densities of erythrocytes, whole-body blood, and of the shifted fluid were computed and the magnitude of fluid and protein shifts were calculated during head-up tilt (60 degrees) with and without application of LBPP. During 30-min head-up tilt with LBPP, blood density (BD) and plasma density (PD) increased by 1.6 +/- 0.3 g.1-1, and by 0.8 +/- 0.2 g.1-1 (+/- SD) (N = 9), respectively. In the subsequent period of tilt without LBPP, BD and PD increased further to + 3.6 +/- 0.9 g.1-1, and to + 2.0 +/- 0.7 g.1-1 (N = 7), compared to supine control. The density increases in both periods were significant (p less than 0.05). Erythrocyte density remained unaltered with changes in body position and pressure suit inflation/deflation. Calculated shifted-fluid densities (FD) during tilt with LBPP (1006.0 +/- 1.1 g.1-1, N = 9), and for subsequent tilt after deflation (1002.8 +/- 4.1 g.1-1, N = 7) were different from each other (p less than 0.03). The plasma volume decreased by 6.0 +/- 1.2% in the tilt-LBPP period, and by an additional 6.4 +/- 2.7% of the supine control level in the subsequent postdeflation tilt period. The corresponding blood volume changes were 3.7 +/- 0.7% (p less than 0.01), and 3.5 +/- 2.1% (p less than 0.05), respectively. Thus, about half of the postural hemo-concentration occurring during passive head-up tilt was prevented by application of 60 mm Hg LBPP.     

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.     

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.     

Human calf microvascular compliance measured by near-infrared spectroscopy.

The purpose of this study is to develop a new method for the measurement in humans of the compliance of the microvascular superficial venous system of the lower limb by near-infrared spectroscopy (NIRS). This method is complementary to strain-gauge plethysmography, which does not allow compliance between deep and superficial venous or between venous and arterial compartments to be distinguished. In practice, hydrostatic pressure (P) changes were induced in a calf region of interest by head-up tilt of the subject from alpha = -10 to 75 degrees. For P < or = 24 mmHg, the measured compliance [0.086 +/- 0.005 (SD) ml. l(-1). mmHg(-1)] based on NIRS data of total, deoxygenated, and oxygenated hemoglobin, reflects essentially that of the superficial venous system. For P > or = 24 mmHg, no distinction can be made between arterial and venous volumes changes. However, by following the changes in oxy- and deoxyhemoglobin in the P range -16 to 100 mmHg, it appears to be possible to assess the characteristics of the vasomotor response of the arteriolar system.     

Hypotensive effect of push-pull gravitational stress occurs after autonomic blockade.

The "push-pull" effect denotes the reduced tolerance to +Gz (hypergravity) when +Gz stress is preceded by exposure to hypogravity, i.e., fractional, zero, or negative Gz. Previous studies have implicated autonomic reflexes as a mechanism contributing to the push-pull effect. The purpose of this study was to test the hypothesis that nonautonomic mechanisms can cause a push-pull effect, by using eye-level blood pressure as a measure of G tolerance. The approach was to impose control (30 s of 30 degrees head-up tilt) and push-pull (30 s of 30 degrees head-up tilt immediately preceded by 10 s of -15 degrees headdown tilt) gravitational stress after administration of hexamethonium (10 mg/kg) to inhibit autonomic ganglionic neurotransmission in four dogs. The animals were chronically instrumented with arterial and venous catheters, an ascending aortic blood flow transducer, ventricular pacing electrodes, and atrioventicular block. The animals were paced at 75 beats/min throughout the experiment. The animals were sedated with acepromazine and lightly restrained in lateral recumbency on a tilt table. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -27.6 +/- 2.3 and -37.9 +/- 2.7 mmHg for the control and push-pull trials, respectively (P < 0.05). Cardiac output fell similarly in both conditions. Thus a push-pull effect attributable to a rise in total vascular conductance occurs when autonomic function is inhibited.     

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.     

Bionic epidural stimulation restores arterial pressure regulation during orthostasis.

A bionic baroreflex system (BBS) is a computer-assisted intelligent feedback system to control arterial pressure (AP) for the treatment of baroreflex failure. To apply this system clinically, an appropriate efferent neural (sympathetic vasomotor) interface has to be explored. We examined whether the spinal cord is a candidate site for such interface. In six anesthetized and baroreflex-deafferentiated cats, a multielectrode catheter was inserted into the epidural space to deliver epidural spinal cord stimulation (ESCS). Stepwise changes in ESCS rate revealed a linear correlation between ESCS rate and AP for ESCS rates of 2 pulses/s and above (r2, 0.876-0.979; slope, 14.3 +/- 5.8 mmHg.pulses(-1).s; pressure axis intercept, 35.7 +/- 25.9 mmHg). Random changes in ESCS rate with a white noise sequence revealed dynamic transfer function of peripheral effectors. The transfer function resembled a second-order, low-pass filter with a lag time (gain, 16.7 +/- 8.3 mmHg.pulses(-1).s; natural frequency, 0.022 +/- 0.007 Hz; damping coefficient, 2.40 +/- 1.07; lag time, 1.06 +/- 0.41 s). On the basis of the transfer function, we designed an artificial vasomotor center to attenuate hypotension. We evaluated the performance of the BBS against hypotension induced by 60 degrees head-up tilt. In the cats with baroreflex failure, head-up tilt dropped AP by 37 +/- 5 mmHg in 5 s and 59 +/- 11 mmHg in 30 s. BBS with optimized feedback parameters attenuated hypotension to 21 +/- 2 mmHg in 5 s (P < 0.05) and 8 +/- 4 mmHg in 30 s (P < 0.05). These results indicate that ESCS-mediated BBS prevents orthostatic hypotension. Because epidural stimulation is a clinically feasible procedure, this BBS can be applied clinically to combat hypotension associated with various pathophysiologies.     

Preserved autonomic function in amenorrheic athletes.

Reproductive hormones such as estradiol and progesterone are known to influence autonomic cardiovascular regulation. The purpose of this study was to determine whether amenorrheic athletes (AA) have impaired autonomic cardiovascular regulation compared with eumenorrheic athletes (EA). Thirty-five athletes were tested: 13 AA (19 +/- 1 yr), 13 EA (21 +/- 1 yr), and 9 EA (23 +/- 1 yr) on oral contraceptives (EA-OC). Multiple indexes of autonomic cardiovascular regulation were assessed: respiratory sinus arrhythmia (RSA), cardiovagal baroreflex sensitivity (BRS) via phase IV and phase II of the Valsalva maneuver, a spontaneous index of BRS, and the heart rate and blood pressure responses to orthostatic stress (20-min 60 degrees head-up tilt). RSA was not different among the groups. There were no group differences in the spontaneous index of BRS (AA = 30 +/- 6, EA = 24 +/- 3, EA-OC = 29 +/- 5 ms/mmHg) or in phase II (AA = 8 +/- 2, EA = 7 +/- 1, EA-OC = 8 +/- 1 ms/mmHg) of the Valsalva. There was a difference in BRS during phase IV (AA = 21 +/- 3, EA = 15 +/- 1, EA-OC = 26 +/- 6 ms/mmHg; ANOVA P = 0.04). Tukey's post hoc test indicated that BRS was greater in the EA-OC group compared with the EA group (P = 0.04). There were no differences in cardiovascular responses to orthostatic stress among the groups. In conclusion, AA do not display signs of impaired autonomic function and orthostatic responses compared with EA or EA-OC during the follicular phase of the menstrual cycle.     

Effects of lower body positive pressure on muscle sympathetic nerve activity response to head-up tilt

The present study was performed to test the hypothesis that application of lower body positive pressure (LBPP) during orthostasis would reduce the baroreflex-mediated enhancement in sympathetic activity in humans. Eight healthy young men were exposed to a 70 degrees head-up tilt (HUT) on application of 30 mmHg LBPP. Muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve, along with hemodynamic variables. We found that in the supine position with LBPP, MSNA remained unchanged (13.4 +/- 3.3 vs. 11.8 +/- 2.3 bursts/min, without vs. with LBPP; P > 0.05), mean arterial pressure was elevated, but arterial pulse pressure and heart rate did not alter. At 70 degrees HUT with LBPP, the enhanced MSNA response was reduced (33.8 +/- 5.0 vs. 22.5 +/- 2.2 bursts/min, without vs. with LBPP; P < 0.05), mean arterial pressure was higher, the decreased pulse pressure was restored, and the increased heart rate was attenuated. We conclude that the baroreflex-mediated enhancement in sympathetic activity during HUT was reduced by LBPP. Application of LBPP in HUT induced an obvious cephalad fluid shift as well as a restoration of arterial pulse pressure, which reduced the inhibition of the baroreceptors. However, the activation of the intramuscular mechanoreflexes produced by 30 mmHg LBPP might counteract the effects of baroreflexes.     

Calf blood flow during prolonged tilt in idiopathic dilated cardiomyopathy and after cardiac transplantation

In severe congestive heart failure (CHF), abnormal reflex control of calf blood flow during brief head-up tilt that appears to normalize after transplantation (HTX) may be present during prolonged observation also. Therefore, we studied the effect of prolonged (30 min) 50 degrees head-up tilt on calf skeletal muscle blood flow measured by the local (133)Xe washout method in CHF and after HTX and in patients with the presence vs. absence of native right atrium (+PNA and -PNA, respectively). During brief head-up tilt, skeletal muscle blood flow increased 13 +/- 42% in 9 severe CHF patients in contrast to a -28 +/- 22% decrease (P < 0.01) in 11 control subjects, -24 +/- 30% decrease in 15 moderate CHF patients (P < 0.05), -25 +/- 14% decrease in 12 patients with recent HTX (P < 0.01), and -21 +/- 24% decrease in 8 patients with distant HTX (P = 0.06). However, during sustained tilt, blood flow declined to similar levels of that in the other groups in severe CHF. HTX -PNA vs. +PNA showed blunted skeletal muscle vasomotor control (P < 0.05) and a higher systolic blood pressure (139 +/- 14 vs. 125 +/- 15 mmHg, P < 0.05) and heart rate (92 +/- 10 vs. 83 +/- 8 beats/min, P < 0.05). Thus paradox vasodilatation of calf skeletal muscle in severe CHF is present only during brief but not prolonged tilt. This may be one explanation of the rare presence of orthostatic intolerance in CHF and implies only a minor possible role for the abnormality in edema pathogenesis. Removal of all right atrium in HTX has an important hemodynamic impact that may possibly affect later clinical outcome.     

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.