Beat-to-beat cardiovascular responses to rapid, low-level LBNP in humans

The hypothesis tested was that there are significant transient changes in the cardiovascular variables after rapid onset and release of mild lower body negative pressure (LBNP, -20 mmHg), even in experimental situations where there is no detectable change in steady-state values. Twelve subjects participated in the study. Heart rate, stroke volume (SV), cardiac output, mean arterial pressure (MAP), total peripheral resistance (TPR), acral and nonacral skin blood flow, and blood flow velocity in the brachial artery were continuously recorded during the pre-LBNP period (0-120 s), during LBNP (120-420 s), and during the post-LBNP period (420-600 s). The main finding was that MAP is transiently but strongly affected by rapid changes in LBNP as small as -20 mmHg. There was also a characteristic asymmetry in cardiovascular responses to the onset and release of LBNP, particularly in the responses in SV. The transient changes in MAP indicate that the neural responses that affect TPR are not fast enough to compensate for the rapid changes in LBNP. In this case, the arterial baroreceptors will be activated as well as the low-pressure baroreceptors that sense central venous pressure. This must be taken into consideration in future discussions of the results of LBNP protocols.     

Hemodynamic and neuroendocrine predictors of lower body negative pressure (LBNP) intolerance in healthy young men.

Exposure to LBNP results in body fluid shift to lower extremities similarly as under influence of orthostatic stress. In susceptible persons it leads to syncope. For better understanding why certain individuals are more susceptible to orthostatic challenges it seemed necessary to collect more data on hemodynamic and neuroendocrine adjustments occurring before onset of presyncopal symptoms Accordingly, in this study heart rate (HR), blood pressure (BP), stroke volume (SV), cardiac output (CO), hematocrit, plasma catecholamines, adrenomedullin, ACTH and plasma renin activity (PRA) were measured in 24 healthy men during graded LBNP (-15, -30 and -50 mmHg). Thirteen subjects completed the test (HT group) whereas 11 had presyncope signs or symptoms at -30 mmHg or at the beginning of -50 mmHg (LT group). Comparison of these groups showed that LT subjects had lower baseline total peripheral resistance and higher plasma adrenomedullin. During LBNP plasma catecholamine and PRA increases were even greater in LT than in HT group while plasma adrenomedullin elevations were similar in both groups. Plasma ACTH increased only in LT group following presyncope symptoms. Low tolerant group showed more rapid decline of SV and CO than HT subjects from the beginning of LBNP. It is suggested that measurements of SV at the level of LBNP which did not evoke any adverse symptoms may be of predictive value for lower orthostatic tolerance.     

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.     

Blood pressure regulation in neurally intact human vs. acutely injured paraplegic and tetraplegic patients during passive tilt

We investigated autonomic control of cardiovascular function in able-bodied (AB), paraplegic (PARA), and tetraplegic (TETRA) subjects in response to head-up tilt following spinal cord injury. We evaluated spectral power of blood pressure (BP), baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), occurrence of systolic blood pressure (SBP) ramps, baroreflex sequences, and cross-correlation of SBP with heart rate (HR) in low (0.04-0.15 Hz)- and high (0.15-0.4 Hz)-frequency regions. During tilt, AB and PARA effectively regulated BP and HR, but TETRA did not. The numbers of SBP ramps and percentages of heartbeats involved in SBP ramps and baroreflex sequences increased in AB, were unchanged in PARA, and declined in TETRA. BRS was lowest in PARA and declined with tilt in all groups. BEI was greatest in AB and declined with tilt in all groups. Low-frequency power of BP and the peak of the SBP/HR cross-correlation magnitude were greatest in AB, increased during tilt in AB, remained unchanged in PARA, and declined in TETRA. The peak cross-correlation magnitude in HF decreased with tilt in all groups. Our data indicate that spinal cord injury results in decreased stimulation of arterial baroreceptors and less engagement of feedback control as demonstrated by lower 1) spectral power of BP, 2) number (and percentages) of SBP ramps and barosequences, 3) cross-correlation magnitude of SBP/HR, 4) BEI, and 5) changes in delay between SBP/HR. Diminished vasomotion and impaired baroreflex regulation may be major contributors to decreased orthostatic tolerance following injury.     

Comparison of cardiovascular responses between lower body negative pressure and head-up tilt.

To investigate local blood-flow regulation during orthostatic maneuvers, 10 healthy subjects were exposed to -20 and -40 mmHg lower body negative pressure (LBNP; each for 3 min) and to 60 degrees head-up tilt (HUT; for 5 min). Measurements were made of blood flow in the brachial (BF(brachial)) and femoral arteries (BF(femoral)) (both by the ultrasound Doppler method), heart rate (HR), mean arterial pressure (MAP), cardiac stroke volume (SV; by echocardiography), and left ventricular end-diastolic volume (LVEDV; by echocardiography). Comparable central cardiovascular responses (changes in LVEDV, SV, and MAP) were seen during LBNP and HUT. During -20 mmHg LBNP, -40 mmHg LBNP, and HUT, the following results were observed: 1) BF(brachial) decreased by 51, 57, and 41%, and BF(femoral) decreased by 40, 53, and 62%, respectively, 2) vascular resistance increased in the upper limb by 110, 147, and 85%, and in the lower limb by 76, 153, and 250%, respectively. The increases in vascular resistance were not different between the upper and lower limbs during LBNP. However, during HUT, the increase in the lower limb was much greater than that in the upper limb. These results suggest that, during orthostatic stimulation, the vascular responses in the limbs due to the cardiopulmonary and arterial baroreflexes can be strongly modulated by local mechanisms (presumably induced by gravitational effects).     

Cardiovascular responses in paraplegic subjects during arm exercise

The purpose of this study was to examine cardiovascular responses during arm exercise in paraplegics compared to a well-matched control group. A group of 11 male paraplegics (P) with complete spinal cord-lesions between T6 and T12 and 11 male control subjects (C), matched for physical activity, sport participation and age performed maximal arm-cranking exercise and submaximal exercise at 20%, 40% and 60% of the maximal load for each individual. Cardiac output (Qc) was determined by the CO2 rebreathing method. Maximal oxygen uptake was significantly lower and maximal heart rate (fc) was significantly higher in P compared to C. At the same oxygen uptakes no significant differences were observed in Qc between P and C; however, stroke volume (SV) was significantly lower and fc significantly higher in P than in C. The lower SV in P could be explained by an impaired redistribution of blood and, therefore, a reduced ventricular filling pressure, due to pooling of venous blood caused by inactivity of the skeletal muscle pump in the legs and lack of sympathetic vasoconstriction below the lesion. In conclusion, in P maximal performance appears to have been limited by a smaller active muscle mass and a lower SV despite the higher fc,max. During submaximal exercise, however, this lower SV was compensated for by a higher fc and, thus at the same submaximal oxygen uptake, Qc was similar to that in the control group.     

Beta-blockade does not improve orthostatic intolerance induced by 20 days bed rest

To assess if propranolol influences orthostatic intolerance induced by prolonged bed rest (BR), a lower body negative pressure test (LBNP) and left ventricular (LV) echocardiography before and during -40mmHg of LBNP were performed with and without intravenous propranolol administration (0.04mg/kg) in 9 healthy volunteers (mean age: 21 years) before and after 20 days BR. LBNP tolerance time (LBNP-T), endpoint heart rate(HR), and percentage changes from 0 to -40mmHg LBNP in HR, LV diastolic dimension(LVDd), stroke volume (SV), cardiac output (CO), and systemic vascular resistance(SVR) were measured. After BR, percentage changes in CO during LBNP was not altered by propranolol (-12+/-21% vs. -24+/-24%; with and without propranolol; p>0.05) because the effect on percentage changes in HR (18+/-11% vs. 26+/-12%; p<0.05) cancelled out the effects of percentage changes in LVDd (-9+/-6% vs. -15+/-10%; p<0.05) and percentage changes in SV (-26+/-16% vs. -39+/-22%; p<0.05). In addition, propranolol decreased end-point HR (85+/-15bpm vs. 119+/-l4bpm; p<0.05) and percentage changes in SVR (25+/-32% vs. 53+/-57%; p<0.05). As a result, LBNP-T after BR was unchanged by propranolol (8.8+/-3.3min vs. 10.8+/-5.0min; p>0.05). In conclusion, propranolol failed to change orthostatic intolerance induced by BR.     

Splanchnic and peripheral vascular resistance during lower body negative pressure (LBNP) and tilt

We tested the hypothesis that vasoconstriction in response to LBNP or head up tilt would be reflected in a reduction in splanchnic (portal vein) blood flow (PVF) and increases in forearm and total peripheral vascular resistance (TPR). Changes in vascular resistance indicators were obtained from measurement of PVF from portal vein cross-sectional area and blood velocity by Doppler ultrasound, from forearm vascular resistance (FVR, by Doppler) and total peripheral resistance (TPR, by impedance cardiography). 21 subjects were tested during LBNP (0, -10, -20 and -30 mmHg) and 9 subjects during tilt (0, 45 and 70 degrees). During progressive LBNP, PVF decreased approximately linearly with LBNP (-30, -48 and -64% at -10, -20 and -30 mmHg) and with tilt angle (-39 and -58% at 45 and 70 degrees). The increase in FVR approximately mirrored these changes during LBNP (20.1, 44.7 and 55.3%) and tilt (45.6 and 63.6%). However, the changes in TPR during LBNP (12.0, 16.9 and 26.4%) and tilt (25.2 and 29.2%) were markedly less. This observation of different percent changes in forearm versus total peripheral resistance might reflect true physiological differences in the forearm (and splanchnic) circulations compared with the whole body, or the data might suggest that impedance cardiography did not provide a reliable indicator of cardiac output and therefore TPR under these conditions. The primary observation in this study was that Doppler ultrasound measurement of portal vein blood flow provided a non-invasive estimate of splanchnic vascular resistance during postural or LBNP challenge and that using the reduction in portal vein flow as an index of increased vasoconstriction paralleled the change in forearm vascular resistance.     

Effect of 6-week endurance training on hemodynamic and neurohormonal responses to lower body negative pressure (LBNP) in healthy young men.

Endurance training is considered as a factor impairing orthostatic tolerance although an improvement and lack of effect have been also reported. The mechanisms of the changes and their relation to initial tolerance of orthostasis are not clear. In the present study, effect of moderate running training on hemodynamic and neurohormonal changes during LBNP, a laboratory test simulating orthostasis, was investigated in subjects with high (HT) and low (LT) tolerance of LBNP. Twenty four male, healthy subjects were submitted to graded LBNP (-15, -30 and -50 mmHg) before and after training. During each test heart rate (HR), stroke volume (SV) and blood pressure, plasma catecholamines, ACTH, adrenomedullin, atrial natriuretic peptide, and renin activity were determined. Basing on initial test, 13 subjects who withstood LBNP at -50 mmHg for 10 min were allocated into HT group and 11 subjects who earlier showed presyncopal symptoms to LT group. Training improved LBNP tolerance in six LT subjects. This was associated with attenuated rate of HR increase and SV decline (before training, at -30 mmHg deltaHR was 21 +/- 4 beats/min and deltaSV - -36+/- 8 ml while after training the respective values were 8 +/- 4 beats/min and -11+/- 6 ml). No differences in hemodynamic response were found in HT subjects and those from LT group whose LBNP tolerance was unchanged. In neither group training affected neurohormonal changes except inhibition of plasma ACTH rise in subjects with improvement of LBNP tolerance. It is concluded that some subjects with low orthostatic tolerance may benefit from moderate training due to improvement of cardiac function regulation.     

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.     

Hysteresis in response to descending and ascending lower-body negative pressure

We have investigated the pattern of fluid redistribution and cardiovascular responses during graduated orthostatic stress. Twelve men, age 30-39 yr, underwent a 25-min lower-body negative pressure (LBNP) test protocol that involved sequential stages of LBNP at -8 mmHg (1 min), -16 mmHg (1 min), -30 mmHg (3 min), -40 mmHg (5 min), -50 mmHg (5 min), -40 mmHg (5 min), -30 mmHg (3 min), -16 mmHg (1 min), and -8 mmHg (1 min). Data were recorded at the end of each stage. For many measured variables values during the descending phase of LBNP (-8 to -40 mmHg) were significantly different from values during the ascending phase of (-40 to -8 mmHg). These differences appear to be due to a component of fluid translocation that occurs during LBNP and cannot be reversed within the duration of the procedure. We hypothesize that this slowly reversed component is sequestration of fluid in the interstitial and lymphatic compartments. In contrast, venous pooling is a rapidly reversible component of fluid movement during LBNP. A scheme describing fluid and cardiovascular responses to LBNP based on these data and the data of other investigators is presented.     

Lower body negative pressure as a tool for research in aerospace physiology and military medicine

Lower body negative pressure (LBNP) has been extensively used for decades in aerospace physiological research as a tool to investigate cardiovascular mechanisms that are associated with or underlie performance in aerospace and military environments. In comparison with clinical stand and tilt tests, LBNP represents a relatively safe methodology for inducing highly reproducible hemodynamic responses during exposure to footward fluid shifts similar to those experienced under orthostatic challenge. By maintaining an orthostatic challenge in a supine posture, removal of leg support (muscle pump) and head motion (vestibular stimuli) during LBNP provides the capability to isolate cardiovascular mechanisms that regulate blood pressure. LBNP can be used for physiological measurements, clinical diagnoses and investigational research comparisons of subject populations and alterations in physiological status. The applications of LBNP to the study of blood pressure regulation in spaceflight, groundbased simulations of low gravity, and hemorrhage have provided unique insights and understanding for development of countermeasures based on physiological mechanisms underlying the operational problems.     

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.     

Effect of lower body negative pressure on orthostatic tolerance and cardiac function during 21 days head-down tilt bed rest

The purpose of the present study was to investigate the changes of orthostatic tolerance and cardiac function during 21 d head-down tilt (HDT) bed rest and effect of lower body negative pressure in the first and the last week in humans. Twelve healthy male volunteers were exposed to -6 degrees HDT bed rest for 21 d. Six subjects received -30 mmHg LBNP sessions for 1 h per day from the 1st to the 7th day and from the 15th to the 21st day of the HDT, and six others served as control. Orthostatic tolerance was assessed by means of standard tilt test. Stroke volume (SV), cardiac output (CO), preejection period (PEP) and left ventricular ejection time (LVET) were measured before and during HDT. Before HDT, all the subjects in the two groups completed the tilt tests. After 10 d and 21 d of HDT, all the subjects of the control group and one subject of the LBNP group could not complete the tilt test due to presyncopal or syncopal symptoms. The mean upright time in the control group (15.0 +/- 3.2 min) was significantly shorter than those in the LBNP group (19.7 +/- 0.9 min). SV and CO decreased significantly in the control group on days 3 and 10 of HDT, but remained unchanged throughout HDT in the LBNP group. A significant increase in PEP/LVET was observed on days 3 and 14 of HDT in both groups. The PEP/LVET in the LBNP group was significantly lower on day 3 of HDT, while LVET in the LBNP group was significantly higher on days 3, 7 and 14 of HDT than those in the control group. The results of this study suggest that brief daily LBNP sessions used in the first and the last weeks of 21 d HDT bed rest were effective in diminished the effect of head-down tilt on orthostatic tolerance, and LBNP might partially improve cardiac pumping function and cardiac systole function.     

Physical fitness and cardiovascular regulation: mechanisms of orthostatic intolerance

We studied three groups of eight men each--high, mid, and low fit (peak O2 consumption 60.0 +/- 0.8, 48.9 +/- 1.0, and 35.7 +/- 0.9 ml.min-1.kg-1)--to determine the mechanism of orthostatic intolerance in endurance athletes. Tolerance was defined by progressive lower body negative pressure (LBNP) to presyncope. Maximal calf vascular conductance (Gmax) was measured. The carotid baroreflex was characterized using both stepwise R-wave-triggered and sustained (2 min) changes in neck chamber pressure. High-fit subjects tended to have lower LBNP tolerance than mid- and low-fit subjects but similar baroreflex responses. Subjects with poor LBNP tolerance had larger stroke volumes (SV) (120 +/- 6 vs. 103 +/- 3 ml) and greater decline in SV with LBNP to -40 mmHg (40 +/- 2 vs. 26 +/- 4%). Stepwise multiple linear regression analysis revealed that Gmax and steady-state gain of the carotid baroreflex contributed significantly toward explaining interindividual variations in LBNP tolerance. Thus endurance athletes may have decreased LBNP tolerance, but apparently not as a simple linear function of aerobic fitness. Orthostatic tolerance depends on complex interactions among functional characteristics that appear both related (Gmax and SV) and unrelated (baroreflex function) to fitness or exercise training.     

Heat stress reduces cerebral blood velocity and markedly impairs orthostatic tolerance in humans

Orthostatic tolerance is reduced in the heat-stressed human. This study tested the following hypotheses: 1) whole body heat stress reduces cerebral blood velocity (CBV) and increases cerebral vascular resistance (CVR); and 2) reductions in CBV and increases in CVR in response to an orthostatic challenge will be greater while subjects are heat stressed. Fifteen subjects were instrumented for measurements of CBV (transcranial ultrasonography), mean arterial blood pressure (MAP), heart rate, and internal temperature. Whole body heating increased both internal temperature (36.4+/-0.1 to 37.3+/-0.1 degrees C) and heart rate (59+/-3 to 90+/-3 beats/min); P<0.001. Whole body heating also reduced CBV (62+/-3 to 53+/-2 cm/s) primarily via an elevation in CVR (1.35+/-0.06 to 1.63+/-0.07 mmHg.cm-1.s; P<0.001. A subset of subjects (n=8) were exposed to lower-body negative pressure (LBNP 10, 20, 30, 40 mmHg) in both normothermic and heat-stressed conditions. During normothermia, LBNP of 30 mmHg (highest level of LBNP achieved by the majority of subjects in both thermal conditions) did not significantly alter CBV, CVR, or MAP. During whole body heating, this LBNP decreased MAP (81+/-2 to 75+/-3 mmHg), decreased CBV (50+/-4 to 39+/-1 cm/s), and increased CVR (1.67+/-0.17 to 1.92+/-0.12 mmHg.cm-1.s); P<0.05. These data indicate that heat stress decreases CBV, and the reduction in CBV for a given orthostatic challenge is greater during heat stress. These outcomes reduce the reserve to buffer further decreases in cerebral perfusion before presyncope. Increases in CVR during whole body heating, coupled with even greater increases in CVR during orthostasis and heat stress, likely contribute to orthostatic intolerance.     

Gender differences in cardiovascular regulation during recovery from exercise.

Are women more susceptible to acute postexercise orthostatic hypotension compared with men? We hypothesized that decreases in arterial pressure during recovery from dynamic exercise are greater in women compared with men. We studied 8 men and 11 women during inactive and active recovery from cycling exercise. Heart rate, stroke volume (SV), cardiac output, mean arterial pressure (MAP), and total peripheral resistance (TPR) were measured during and after 3 min of exercise at 60% of calculated maximum heart rate. At 1 min after exercise, MAP decreased less (P < 0.05) during inactive recovery in men (-18 +/- 2 mmHg) compared with women (-30 +/- 2 mmHg). This difference was due to greater decreases in SV and less increase in TPR during inactive recovery from exercise in women compared with men. These differences persisted for 5 min after exercise. MAP decreased less during active recovery in men compared with women. These findings suggest that women may have increased risk of postexercise orthostatic hypotension and that active recovery from exercise may reduce this risk.     

Vestibulosympathetic reflex during orthostatic challenge in aging humans

Aging attenuates the increase in muscle sympathetic nerve activity (MSNA) and elicits hypotension during otolith organ engagement in humans. The purpose of the present study was to determine the neural and cardiovascular responses to otolithic engagement during orthostatic stress in older adults. We hypothesized that age-related impairments in the vestibulosympathetic reflex would persist during orthostatic challenge in older subjects and might compromise arterial blood pressure regulation. MSNA, arterial blood pressure, and heart rate responses to head-down rotation (HDR) performed with and without lower body negative pressure (LBNP) in prone subjects were measured. Ten young (27 +/- 1 yr) and 11 older subjects (64 +/- 1 yr) were studied prospectively. HDR performed alone elicited an attenuated increase in MSNA in older subjects (Delta106 +/- 28 vs. Delta20 +/- 7% for young and older subjects). HDR performed during simultaneous orthostatic stress increased total MSNA further in young (Delta53 +/- 15%; P < 0.05) but not older subjects (Delta-5 +/- 4%). Older subjects demonstrated consistent significant hypotension during HDR performed both alone (Delta-6 +/- 2 mmHg) and during LBNP (Delta-7 +/- 2 mmHg). These data provide experimental support for the concept that age-related impairments in the vestibulosympathetic reflex persist during orthostatic challenge in older adults. Furthermore, these findings are consistent with the concept that age-related alterations in vestibular function might contribute to altered orthostatic blood pressure regulation with age in humans.     

Effect of sleep restriction on orthostatic cardiovascular control in humans.

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

Evidence for sympatholysis at the onset of forearm exercise.

The effect of augmented sympathetic outflow on forearm vascular conductance after single handgrip contractions of graded intensity was examined to determine whether sympatholysis occurs early in exercise (n = 7). While supine, subjects performed contractions that were 1 s in duration and 15, 30, and 60% of maximal voluntary contraction (MVC) in intensity. The contractions were repeated during control and lower body negative pressure (LBNP) (-40 mmHg) sessions. Forearm blood flow (FBF; Doppler ultrasound) and mean arterial pressure were measured continuously for 30 s before and 60 s after the single contractions. Vascular conductance (VC) was calculated. Total postcontraction blood flow increased in an exercise intensity-dependent manner. Compared with control, LBNP caused a reduction in baseline and postexercise FBF (P < 0.05), VC (P < 0.01), as well as total excess flow (P < 0.01). Specifically, during LBNP, baseline FBF and VC were reduced by 29 and 34% of control, respectively (P < 0.05). After the 15% MVC contraction, peak VC during LBNP was reduced by a magnitude similar to that during baseline (i.e., ~30%), but it was only reduced by 15% during both the 30 and 60% MVC trials (P < 0.01). It was concluded that the stimuli for exercise hyperemia during moderate and heavy, but not mild, handgrip exercise intensities, diminish the vasoconstrictor effects of LBNP. Furthermore, these data demonstrate that this sympatholysis occurs early in exercise.