Short-term variability of blood pressure: effects of lower-body negative pressure and long-duration bed rest

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

Dynamic autoregulation of cutaneous circulation: differential control in glabrous versus nonglabrous skin

The purpose of this project was to test the hypothesis that, independent of neural control, glabrous and nonglabrous cutaneous vasculature is capable of autoregulating blood flow. In 10 subjects, spectral and transfer function analyses of arterial pressure and skin blood flow (laser-Doppler flowmetry) from glabrous (palm) and nonglabrous (forearm) regions were performed under three conditions: baseline, ganglionic blockade via intravenous trimethaphan administration, and trimethaphan plus oscillatory lower body negative pressure (LBNP; -5 to -10 mmHg) from 0.05 to 0.07 Hz. Oscillatory LBNP was applied to regenerate mean arterial pressure variability that was abolished by ganglionic blockade. Ganglionic blockade was verified by an absence of a heart rate response to a Valsalva maneuver. Spectral power and transfer function gain between blood pressure and skin blood flow were calculated in this oscillatory frequency range (0.05-0.07 Hz). Within this frequency range, ganglionic blockade significantly decreased spectral power of blood flow in both the forearm and palm, whereas regeneration of arterial blood pressure oscillations significantly increased spectral power of forearm blood flow but not palm blood flow. During oscillatory LBNP, transfer function gain between blood pressure and skin blood flow was significantly elevated at the forearm (0.28 +/- 0.03 to 0.53 +/- 0.02 flux units/mmHg; P < 0.05) but was reduced at the palm (4.7 +/- 0.5 to 1.2 +/- 0.1 flux units/mmHg; P < 0.05). These data show that independent of neural control of blood flow, glabrous skin has the ability to buffer blood pressure oscillations and demonstrates a degree of dynamic autoregulation. Conversely, these data suggest that nonglabrous skin has diminished dynamic autoregulatory capabilities.     

Sex differences in hemodynamic and sympathetic neural firing patterns during orthostatic challenge in humans

Recent evidence suggests that young men and women may have different strategies for regulating arterial blood pressure, and the purpose of the present study was to determine if sex differences exist in diastolic arterial pressure (DAP) and muscle sympathetic nerve activity (MSNA) relations during simulated orthostatic stress. We hypothesized that young men would demonstrate stronger DAP-MSNA coherence and a greater percentage of "consecutive integrated bursts" during orthostatic stress. Fourteen men and 14 women (age 23 ± 1 yr) were examined at rest and during progressive lower body negative pressure (LBNP; -5 to -40 mmHg). Progressive LBNP did not alter mean arterial pressure (MAP) in either sex. Heart rate increased and stroke volume decreased to a greater extent during LBNP in women (interactions, P < 0.05). DAP-MSNA coherence was strong (i.e., r ≥ 0.5) at rest and increased throughout all LBNP stages in men. In contrast, DAP-MSNA coherence was lower in women, and responses to progressive LBNP were attenuated compared with men (time × sex, P = 0.029). Men demonstrated a higher percentage of consecutive bursts during all stages of LBNP (sex, P < 0.05), although the percentage of consecutive bursts increased similarly during progressive LBNP between sexes. In conclusion, men and women demonstrate different firing patterns of integrated MSNA during LBNP that appear to be related to differences in DAP oscillatory patterns. Men tend to have more consecutive bursts, which likely contribute to a stronger DAP-MSNA coherence. These findings may help explain why young women are more prone to orthostatic intolerance.     

Vagal cardiac function and arterial blood pressure stability

This study was designed to investigate the importance of vagal cardiac modulation in arterial blood pressure (ABP) stability before and after glycopyrrolate or atropine treatment. Changes in R-R interval (RRI) and ABP were assessed in 10 healthy young (age, 22 +/- 1.8 yr) volunteers during graded lower body negative pressure (LBNP) before and after muscarinic cholinergic (MC) blockade. Transient hypertension was induced by phenylephrine (1 microg/kg body wt), whereas systemic hypotension was induced by bilateral thigh cuff deflation after a 3-min suprasystolic occlusion. Power spectral densities of systolic [systolic blood pressure (SBP)] and diastolic ABP variability were examined. Both antimuscarinic agents elicited tachycardia similarly without significantly affecting baseline ABP. The increase in SBP after phenylephrine injection (+14 +/- 2 mmHg) was significantly augmented with atropine (+26 +/- 2 mmHg) or glycopyrrolate (+27 +/- 3 mmHg) and associated with a diminished reflex bradycardia. The decrease in SBP after cuff deflation (-9.2 +/- 1.2 mmHg) was significantly greater after atropine (-15 +/- 1 mmHg) or glycopyrrolate (-14 +/- 1 mmHg), with abolished reflex tachycardia. LBNP significantly decreased both SBP and RRI. However, after antimuscarinic agents, the reduction in SBP was greater (P < 0.05) and was associated with less tachycardia. Antimuscarinic agents reduced (P < 0.05) the low-frequency (LF; 0.04-0.12 Hz) power of ABP variability at rest. The LF SBP oscillation was significantly augmented during LBNP, which was accentuated (P < 0.05) after antimuscarinic agents and was correlated (r = -0.79) with the decrease in SBP. We conclude that antimuscarinic agents compromised ABP stability by diminishing baroreflex sensitivity, reflecting the importance of vagal cardiac function in hemodynamic homeostasis. The difference between atropine and glycopyrrolate was not significant.     

Muscle sympathetic nerve activity during lower body negative pressure is accentuated in heat-stressed humans.

The purpose of this project was to test the hypothesis that increases in muscle sympathetic nerve activity (MSNA) during an orthostatic challenge is attenuated in heat-stressed individuals. To accomplish this objective, MSNA was measured during graded lower body negative pressure (LBNP) in nine subjects under normothermic and heat-stressed conditions. Progressive LBNP was applied at -3, -6, -9, -12, -15, -18, -21, and -40 mmHg for 2 min per stage. Whole body heating caused significant increases in sublingual temperature, skin blood flow, sweat rate, heart rate, and MSNA (all P < 0.05) but not in mean arterial blood pressure (P > 0.05). Progressive LBNP induced significant increases in MSNA in both thermal conditions. However, during the heat stress trial, increases in MSNA at LBNP levels higher than -9 mmHg were greater compared with during the same LBNP levels in normothermia (all P < 0.05). These data suggest that the increase in MSNA to orthostatic stress is not attenuated but rather accentuated in heat-stressed humans.     

Effects of lower body negative pressure on cardiac and vascular responses to carotid baroreflex stimulation

The aim of this study was to assess carotid baroreflex responses during graded lower body negative pressure (LBNP). In 12 healthy subjects (age 29+/-4 years) we applied sinusoidal neck suction (0 to -30 mmHg) at 0.1 Hz to examine the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Responses to neck suction were determined as the change in spectral power of RR-interval and blood pressure from baseline values. Measurements were carried out during progressive applications (0 to -50 mmHg) of LBNP. Responses to 0.1 and 0.2 Hz carotid baroreceptor stimulations during low levels of LBNP (-10 mmHg) were not significantly different from those measured during baseline. At higher levels of LBNP, blood pressure responses to 0.1 Hz neck suction were significantly enhanced, but with no significant change in the RR-interval response. LBNP at all levels had no effect on the RR-interval response to 0.2 Hz neck suction. The unchanged responses of RR-interval and blood pressure to neck suction during low level LBNP at -10 mmHg suggest no effect of cardiopulmonary receptor unloading on the carotid arterial baroreflex, since this LBNP level is considered to stimulate cardiopulmonary but not arterial baroreflexes. Enhanced blood pressure responses to neck suction during higher levels of LBNP are not necessarily the result of a reflex interaction but may serve to protect the circulation from fluctuations in blood pressure while standing.     

Does nitric oxide buffer arterial blood pressure variability in humans?

Animal studies suggest that nitric oxide (NO) plays an important role in buffering short-term arterial pressure variability, but data from humans addressing this hypothesis are scarce. We evaluated the effects of NO synthase (NOS) inhibition on arterial blood pressure (BP) variability in eight healthy subjects in the supine position and during 60 degrees head-up tilt (HUT). Systemic NOS was blocked by intravenous infusion of N(G)-monomethyl-L-arginine (L-NMMA). Electrocardiogram and beat-by-beat BP in the finger (Finapres) were recorded continuously for 6 min, and brachial cuff BP was recorded before and after L-NMMA in each body position. BP and R-R variability and their transfer functions were quantified by power spectral analysis in the low-frequency (LF; 0.05-0.15 Hz) and high-frequency (HF; 0.15-0.35 Hz) ranges. L-NMMA infusion increased supine BP (systolic, 109 +/- 4 vs. 122 +/- 3 mmHg, P = 0.03; diastolic, 68 +/- 2 vs. 78 +/- 3 mmHg, P = 0.002), but it did not affect supine R-R interval or BP variability. Before L-NMMA, HUT decreased HF R-R variability (P = 0.03), decreased transfer function gain (LF, 12 +/- 2 vs. 5 +/- 1 ms/mmHg, P = 0.007; HF, 18 +/- 3 vs. 3 +/- 1 ms/mmHg, P = 0.002), and increased LF BP variability (P < 0.0001). After L-NMMA, HUT resulted in similar changes in BP and R-R variability compared with tilt without L-NMMA. Increased supine BP after L-NMMA with no effect on BP variability during HUT suggests that tonic release of NO is important for systemic vascular tone and thus steady-state arterial pressure, but NO does not buffer dynamic BP oscillations in humans.     

Detection of low- and high-frequency rhythms in the variability of skin sympathetic nerve activity

Spectral analysis of skin blood flow has demonstrated low-frequency (LF, 0.03-0.15 Hz) and high-frequency (HF, 0.15-0.40 Hz) oscillations, similar to oscillations in R-R interval, systolic pressure, and muscle sympathetic nerve activity (MSNA). It is not known whether the oscillatory profile of skin blood flow is secondary to oscillations in arterial pressure or to oscillations in skin sympathetic nerve activity (SSNA). MSNA and SSNA differ markedly with regard to control mechanisms and morphology. MSNA contains vasoconstrictor fibers directed to muscle vasculature, closely regulated by baroreceptors. SSNA contains both vasomotor and sudomotor fibers, differentially responding to arousals and thermal stimuli. Nevertheless, MSNA and SSNA share certain common characteristics. We tested the hypothesis that LF and HF oscillatory components are evident in SSNA, similar to the oscillatory components present in MSNA. We studied 18 healthy normal subjects and obtained sequential measurements of MSNA and SSNA from the peroneal nerve during supine rest. Measurements were also obtained of the electrocardiogram, beat-by-beat blood pressure (Finapres), and respiration. Spectral analysis showed LF and HF oscillations in MSNA, coherent with similar oscillations in both R-R interval and systolic pressure. The HF oscillation of MSNA was coherent with respiration. Similarly, LF and HF spectral components were evident in SSNA variability, coherent with corresponding variability components of R-R interval and systolic pressure. HF oscillations of SSNA were coherent with respiration. Thus our data suggest that these oscillations may be fundamental characteristics shared by MSNA and SSNA, possibly reflecting common central mechanisms regulating sympathetic outflows subserving different regions and functions.     

Tolerance to central hypovolemia: the influence of oscillations in arterial pressure and cerebral blood velocity

Higher oscillations of cerebral blood velocity and arterial pressure (AP) induced by breathing with inspiratory resistance are associated with delayed onset of symptoms and increased tolerance to central hypovolemia. We tested the hypothesis that subjects with high tolerance (HT) to central hypovolemia would display higher endogenous oscillations of cerebral blood velocity and AP at presyncope compared with subjects with low tolerance (LT). One-hundred thirty-five subjects were exposed to progressive lower body negative pressure (LBNP) until the presence of presyncopal symptoms. Subjects were classified as HT if they completed at least the -60-mmHg level of LBNP (93 subjects; LBNP time, 1,880 ± 259 s) and LT if they did not complete this level (42 subjects; LBNP time, 1,277 ± 199 s). Middle cerebral artery velocity (MCAv) was measured by transcranial Doppler, and AP was measured at the finger by photoplethysmography. Mean MCAv and mean arterial pressure (MAP) decreased progressively from baseline to presyncope for both LT and HT subjects (P < 0.001). However, low frequency (0.04-0.15 Hz) oscillations of mean MCAv and MAP were higher at presyncope in HT subjects compared with LT subjects (MCAv: HT, 7.2 ± 0.7 vs. LT, 5.3 ± 0.6 (cm/s)(2), P = 0.075; MAP: HT, 15.3 ± 1.4 vs. 7.9 ± 1.2 mmHg(2), P < 0.001). Consistent with our previous findings using inspiratory resistance, high oscillations of mean MCAv and MAP are associated with HT to central hypovolemia.     

Respiratory modulation of human autonomic rhythms

We studied the influence of three types of breathing [spontaneous, frequency controlled (0.25 Hz), and hyperventilation with 100% oxygen] and apnea on R-R interval, photoplethysmographic arterial pressure, and muscle sympathetic rhythms in nine healthy young adults. We integrated fast Fourier transform power spectra over low (0.05-0.15 Hz) and respiratory (0.15-0.3 Hz) frequencies; estimated vagal baroreceptor-cardiac reflex gain at low frequencies with cross-spectral techniques; and used partial coherence analysis to remove the influence of breathing from the R-R interval, systolic pressure, and muscle sympathetic nerve spectra. Coherence among signals varied as functions of both frequency and time. Partialization abolished the coherence among these signals at respiratory but not at low frequencies. The mode of breathing did not influence low-frequency oscillations, and they persisted during apnea. Our study documents the independence of low-frequency rhythms from respiratory activity and suggests that the close correlations that may exist among arterial pressures, R-R intervals, and muscle sympathetic nerve activity at respiratory frequencies result from the influence of respiration on these measures rather than from arterial baroreflex physiology. Most importantly, our results indicate that correlations among autonomic and hemodynamic rhythms vary over time and frequency, and, thus, are facultative rather than fixed.     

Reflex control of the cutaneous circulation during passive body core heating in humans.

The impact of body core heating on the interaction between the cutaneous and central circulation during blood pressure challenges was examined in eight adults. Subjects were exposed to -10 to -90 mmHg lower body negative pressure (LBNP) in thermoneutral conditions and -10 to -60 mmHg LBNP during heat stress. We measured forearm vascular conductance (FVC; ml. min(-1). 100 ml(-1). mmHg(-1)) by plethysmography; cutaneous vascular conductance (CVC) by laser-Doppler techniques; and central venous pressure, arterial blood pressure, and cardiac output by impedance cardiography. Heat stress increased FVC from 5.7 +/- 0.9 to 18.8 +/- 1.3 conductance units (CU) and CVC from 0.21 +/- 0.07 to 1.02 +/- 0.20 CU. The FVC-CVP relationship was linear over the entire range of LBNP and was shifted upward during heat stress with a slope increase from 0. 46 +/- 0.10 to 1.57 +/- 0.3 CU/mmHg CVP (P < 0.05). Resting CVP was lower during heat stress (6.3 +/- 0.6 vs. 7.7 +/- 0.6 mmHg; P < 0. 05) but fell to similar levels during LBNP as in normothermic conditions. Data analysis indicates an increased capacity, but not sensitivity, of peripheral baroreflex responses during heat stress. Laser-Doppler techniques detected thermoregulatory responses in the skin, but no significant change in CVC occurred during mild-to-moderate LBNP. Interestingly, very high levels of LBNP produced cutaneous vasodilation in some subjects.     

Influence of acute alcohol ingestion on sympathetic neural responses to orthostatic stress in humans

Acute alcohol consumption is reported to decrease mean arterial pressure (MAP) during orthostatic challenge, a response that may contribute to alcohol-mediated syncope. Muscle sympathetic nerve activity (MSNA) increases during orthostatic stress to help maintain MAP, yet the effects of alcohol on MSNA responses during orthostatic stress have not been determined. We hypothesized that alcohol ingestion would blunt arterial blood pressure and MSNA responses to lower body negative pressure (LBNP). MAP, MSNA, and heart rate (HR) were recorded during progressive LBNP (-5, -10, -15, -20, -30, and -40 mmHg; 3 min/stage) in 30 subjects (age 24 ± 1 yr). After an initial progressive LBNP (pretreatment), subjects consumed either alcohol (0.8 g ethanol/kg body mass; n = 15) or placebo (n = 15), and progressive LBNP was repeated (posttreatment). Alcohol increased resting HR (59 ± 2 to 65 ± 2 beats/min, P < 0.05), MSNA (13 ± 3 to 19 ± 4 bursts/min, P < 0.05), and MSNA burst latency (1,313 ± 16 to 1,350 ± 17 ms, P < 0.05) compared with placebo (group × treatment interactions, P < 0.05). During progressive LBNP, a pronounced decrease in MAP was observed after alcohol but not placebo (group × time × treatment, P < 0.05). In contrast, MSNA and HR increased during all LBNP protocols, but there were no differences between trials or groups. However, alcohol altered MSNA burst latency response to progressive LBNP. In conclusion, the lack of MSNA adjustment to a larger drop in arterial blood pressure during progressive LBNP, coupled with altered sympathetic burst latency responses, suggests that alcohol blunts MSNA responses to orthostatic stress.     

Heart rate variability and spontaneous baroreflex sequences in supine healthy volunteers subjected to nasal positive airway pressure.

To determine the dynamic effects of short-term nasal positive airway pressure (nPAP) on cardiovascular autonomic control, continuous recordings of noninvasively obtained hemodynamic measurements and heart rate variability (HRV) were obtained in 10 healthy subjects during frequency-controlled breathing (between 0.20 and 0.24 Hz) in supine posture under different pressures of nPAP ranging from 3 to 20 cmH(2)O. HRV was assessed using spectral analysis of the R-R interval. The slope of the regression line between spontaneous systolic blood pressure and pulse interval changes was taken as an index of the sensitivity of arterial baroreflex modulation of heart rate (sequence method). Application of nPAP resulted in a pressure-dependent decrease of cardiac output and stroke volume (P < 0.05, ANOVA) and in an increase in total peripheral resistance (P < 0.03, ANOVA). Hemodynamic changes under increasing nPAP were accompanied by a decrease in total power of HRV despite mean R-R interval remaining unchanged. The overall decrease in HRV was accompanied by a reduction across all frequency bands when absolute units were used (P < 0.01). When the power of low frequency and high frequency was calculated in normalized units, a diminished high frequency and an increased low-to-high frequency ratio were observed (P < 0.05). Compared with low levels of nPAP, pressure levels of >10 cmH(2)O were associated with a significant decline in the mean slope of spontaneous baroreceptor sequences (P < 0.04). These findings indicate that short-term administration of nPAP in normal subjects exerts significant alterations in R-R interval variability and spontaneous baroreflex modulation of heart rate.     

Head-down bed rest impairs vagal baroreflex responses and provokes orthostatic hypotension

We studied vagally mediated carotid baroreceptor-cardiac reflexes in 11 healthy men before, during, and after 30 days of 6 degrees head-down bed rest to test the hypothesis that baroreflex malfunction contributes to orthostatic hypotension in this model of simulated microgravity. Sigmoidal baroreflex response relationships were provoked with ramped neck pressure-suction sequences comprising pressure elevations to 40 mmHg followed by serial R-wave-triggered 15-mmHg reductions to -65 mmHg. Each R-R interval was plotted as a function of systolic pressure minus the neck chamber pressure applied during the interval. Compared with control measurements, base-line R-R intervals and the minimum, maximum, range, and maximum slope of the R-R interval-carotid pressure relationships were reduced (P less than 0.05) from bed rest day 12 through recovery day 5. Baroreflex slopes were reduced more in four subjects who fainted during standing after bed rest than in six subjects who did not faint (-1.8 +/- 0.7 vs. -0.3 +/- 0.3 ms/mmHg, P less than 0.05). There was a significant linear correlation (r = 0.70, P less than 0.05) between changes of baroreflex slopes from before bed rest to bed rest day 25 and changes of systolic blood pressure during standing after bed rest. Although plasma volume declined by approximately 15% (P less than 0.05), there was no significant correlation between reductions of plasma volume and changes of baroreflex responses. There were no significant changes of before and after plasma norepinephrine or epinephrine levels before and after bed rest during supine rest or sitting.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.     

Intrapericardial denervation: radial artery blood flow and heart rate responses to LBNP

Eight rhesus monkeys were used to study responses of radial artery blood flow velocity (RABFV) and heart rate (HR) to low (0 to -20 mmHg) and high (0 to -60 mmHg) ramp exposures during supine lower body negative pressure (LBNP). These levels were chosen to separate peripheral vascular responses associated with stimulation of low- and high-pressure baroreceptors. Four monkeys had efferent and afferent cardiac denervation by use of the Randall procedure with pharmacological (phenylephrine and atropine) verification. Animals were studied 3 wk after surgery to avoid reinnervation. Findings were compared with those of four identically treated intact animals. Denervated animals showed no change in RABFV or HR during low-level LBNP; however, HR increased significantly (P less than 0.05) when LBNP reached -50 mmHg and blood flow velocity also fell (P less than 0.05) starting at -30 mmHg pressure. In contrast, intact animals showed steady decreases in RABFV during both high- and low-pressure protocols, with HR showing a 6-beat/min increase (P less than 0.05) starting at -20 mmHg pressure. As with denervated animals, intact animals showed a more pronounced increase in HR after reaching a level of -60 mmHg suction. Cardiac output (electromagnetic flowmeter, ascending aorta) fell significantly in both groups starting at -30 mmHg pressure. Left ventricular pressure (Konigsberg pressure cell) in three intact animals showed a progressive fall in systolic pressure starting at -10 mmHg suction, which became significant at -55 mmHg pressure. These results demonstrate that cardiac denervation by use of the Randall technique significantly affects RABFV and HR responses to LBNP in rhesus monkeys. The lack of RABFV change during LBNP in denervated animals suggests that these changes coupled with HR response can be used as an effective method to verify the completeness of denervation of low-pressure baroreceptors in animals that have undergone intrapericardial denervation.     

Hemodynamics of orthostatic intolerance: implications for gender differences

Women have a greater incidence of orthostatic intolerance than men. We hypothesized that this difference is related to hemodynamic effects on regulation of cardiac filling rather than to reduced responsiveness of vascular resistance during orthostatic stress. We constructed Frank-Starling curves from pulmonary capillary wedge pressure (PCWP), stroke volume (SV), and stroke index (SI) during lower body negative pressure (LBNP) and saline infusion in 10 healthy young women and 13 men. Orthostatic tolerance was determined by progressive LBNP to presyncope. LBNP tolerance was significantly lower in women than in men (626.8 +/- 55.0 vs. 927.7 +/- 53.0 mmHg x min, P < 0.01). Women had steeper maximal slopes of Starling curves than men whether expressed as SV (12.5 +/- 2.0 vs. 7.1 +/- 1.5 ml/mmHg, P < 0.05) or normalized as SI (6.31 +/- 0.8 vs. 4.29 +/- 0.6 ml.m-2.mmHg-1, P < 0.05). During progressive LBNP, PCWP dropped quickly at low levels, and reached a plateau at high levels of LBNP near presyncope in all subjects. SV was 35% and SI was 29% lower in women at presyncope (both P < 0.05). Coincident with the smaller SV, women had higher heart rates but similar mean arterial pressures compared with men at presyncope. Vascular resistance and plasma norepinephrine concentration were similar between genders. We conclude that lower orthostatic tolerance in women is associated with decreased cardiac filling rather than reduced responsiveness of vascular resistance during orthostatic challenges. Thus cardiac mechanics and Frank-Starling relationship may be important mechanisms underlying the gender difference in orthostatic tolerance.     

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.     

Effect of skin surface cooling on central venous pressure during orthostatic challenge

Orthostatic stress leads to a reduction in central venous pressure (CVP), which is an index of cardiac preload. Skin surface cooling has been shown to improve orthostatic tolerance, although the mechanism resulting in this outcome is unclear. One possible mechanism may be that skin surface cooling attenuates the drop in CVP during an orthostatic challenge, thereby preserving cardiac filling. To test this hypothesis, CVP, arterial blood pressure, heart rate, and skin blood flow, as well as skin and sublingual temperatures, were recorded in nine healthy subjects during lower body negative pressure (LBNP) in both normothermic and skin surface cooling conditions. Cardiac output was also measured via acetylene rebreathing. Progressive LBNP was applied at -10, -15, -20, and -40 mmHg at 5 min/stage. Before LBNP, skin surface cooling lowered mean skin temperature, increased CVP, and increased mean arterial blood pressure (all P < 0.001) but did not change mean heart rate (P = 0.38). Compared with normothermic conditions, arterial blood pressure remained elevated throughout progressive LBNP. Although progressive LBNP decreased CVP under both thermal conditions, during cooling CVP at each stage of LBNP was significantly greater relative to normothermia. Moreover, at higher levels of LBNP with skin cooling, stroke volume was significantly greater relative to normothermic conditions. These data indicate that skin surface cooling induced an upward shift in CVP throughout LBNP, which may be a key factor for preserving preload, stroke volume, and blood pressure and improving orthostatic tolerance.     

Effects of lower body negative pressure on sympathetic discharge to leg muscles in humans

Recent studies indicate that nonhypotensive orthostatic stress in humans causes reflex vasoconstriction in the forearm but not in the calf. We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in conscious humans to determine if unloading of cardiac baroreceptors during nonhypotensive lower body negative pressure (LBNP) increases sympathetic discharge to the leg muscles. LBNP from -5 to -15 mmHg had no effect on arterial pressure or heart rate but caused graded decreases in central venous pressure and corresponding large increases in peroneal MSNA. Total MSNA (burst frequency X mean burst amplitude) increased by 61 +/- 22% (P less than 0.05 vs. control) during LBNP at only -5 mmHg and rose progressively to a value that was 149 +/- 29% greater than control during LBNP at -15 mmHg (P less than 0.05). The major new conclusion is that nonhypotensive LBNP is a potent stimulus to muscle sympathetic outflow in the leg as well as the arm. During orthostatic stress in humans, the cardiac baroreflex appears to trigger a mass sympathetic discharge to the skeletal muscles in all of the extremities.