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.     

Carotid baroreflex responsiveness in heat-stressed humans

The effects of whole body heating on human baroreflex function are relatively unknown. The purpose of this project was to identify whether whole body heating reduces the maximal slope of the carotid baroreflex. In 12 subjects, carotid-vasomotor and carotid-cardiac baroreflex responsiveness were assessed in normothermia and during whole body heating. Whole body heating increased sublingual temperature (from 36.4 +/- 0.1 to 37.4 +/- 0.1 degrees C, P < 0.01) and increased heart rate (from 59 +/- 3 to 83 +/- 3 beats/min, P < 0. 01), whereas mean arterial blood pressure (MAP) was slightly decreased (from 88 +/- 2 to 83 +/- 2 mmHg, P < 0.01). Carotid-vasomotor and carotid-cardiac responsiveness were assessed by identifying the maximal gain of MAP and heart rate to R wave-triggered changes in carotid sinus transmural pressure. Whole body heating significantly decreased the responsiveness of the carotid-vasomotor baroreflex (from -0.20 +/- 0.02 to -0.13 +/- 0.02 mmHg/mmHg, P < 0.01) without altering the responsiveness of the carotid-cardiac baroreflex (from -0.40 +/- 0.05 to -0.36 +/- 0.02 beats x min(-1) x mmHg(-1), P = 0.21). Carotid-vasomotor and carotid-cardiac baroreflex curves were shifted downward and upward, respectively, to accommodate the decrease in blood pressure and increase in heart rate that accompanied the heat stress. Moreover, the operating point of the carotid-cardiac baroreflex was shifted closer to threshold (P = 0.02) by the heat stress. Reduced carotid-vasomotor baroreflex responsiveness, coupled with a reduction in the functional reserve for the carotid baroreflex to increase heart rate during a hypotensive challenge, may contribute to increased susceptibility to orthostatic intolerance during a heat stress.     

Hypohydration and prior heat stress exacerbates decreases in cerebral blood flow velocity during standing.

Hypohydration is associated with orthostatic intolerance; however, little is known about cerebrovascular mechanisms responsible. This study examined whether hypohydration reduces cerebral blood flow velocity (CBFV) in response to an orthostatic challenge. Eight subjects completed four orthostatic challenges (temperate conditions) twice before (Pre-EU and Pre-Hyp) and following recovery from passive heat stress ( approximately 3 h at 45 degrees C, 50% relative humidity, 1 m/s air speed) with (Post-EU) or without (Post-Hyp) fluid replacement of sweat losses (-3% body mass loss). Measurements included CBFV, mean arterial pressure (MAP), heart rate (HR), end-tidal CO(2), and core and skin temperatures. Test sessions included being seated (20 min) followed by standing (60 s) then resitting (60 s) with metronomic breathing (15 breaths/min). CBFV and MAP responses to standing were similar during Pre-EU and Pre-Hyp. Standing Post-Hyp exacerbated the magnitude (-28.0 +/- 1.4% of baseline) and duration (9.0 +/- 1.6 s) of CBFV reductions and increased cerebrovascular resistance (CVR) compared with Post-EU (-20.0 +/- 2.1% and 6.6 +/- 0.9 s). Standing Post-EU also resulted in a reduction in CBFV, and a smaller decrease in CVR compared with Pre-EU. MAP decreases were similar for Post-EU (-18 +/- 4 mmHg) and Post-Hyp (-21 +/- 5 mmHg) from seated to standing. These data demonstrate that despite similar MAP decreases, hypohydration, and prior heat stress (despite apparent recovery) produce greater CBFV reduction when standing. These observations suggest that hypohydration and prior heat stress are associated with greater reductions in CBFV with greater CVR, which likely contribute to orthostatic intolerance.     

Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P < 0.001) without significantly affecting the gain in the low-frequency range (P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.     

Phenylephrine-induced elevations in arterial blood pressure are attenuated in heat-stressed humans

To test the hypothesis that phenylephrine-induced elevations in blood pressure are attenuated in heat-stressed humans, blood pressure was elevated via steady-state infusion of three doses of phenylephrine HCl in 10 healthy subjects in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature by ~0.5 degrees C, muscle sympathetic nerve activity (MSNA), heart rate, and cardiac output and decreased total peripheral vascular resistance (TPR; all P < 0.005) but did not change mean arterial blood pressure (MAP; P > 0.05). At the highest dose of phenylephrine, the increase in MAP and TPR from predrug baselines was significantly attenuated during the heat stress [DeltaMAP 8.4 +/- 1.2 mmHg; DeltaTPR 0.96 +/- 0.85 peripheral resistance units (PRU)] compared with normothermia (DeltaMAP 15.4 +/- 1.4 mmHg, DeltaTPR 7.13 +/- 1.18 PRU; all P < 0.001). The sensitivity of baroreflex control of MSNA and heart rate, expressed as the slope of the relationship between MSNA and diastolic blood pressure, as well as the slope of the relationship between heart rate and systolic blood pressure, respectively, was similar between thermal conditions (each P > 0.05). These data suggest that phenylephrine-induced elevations in MAP are attenuated in heat-stressed humans without affecting baroreflex control of MSNA or heart rate.     

Orthostatic hypotension in aging humans

We tested the hypothesis that hypotension occurred in older adults at the onset of orthostatic challenge as a result of vagal dysfunction. Responses of heart rate (HR) and mean arterial pressure (MAP) were compared between 10 healthy older and younger adults during onset and sustained lower body negative pressure (LBNP). A younger group was also assessed after blockade of the parasympathetic nervous system with the use of atropine or glycopyrrolate and after blockade of the beta(1)-adrenoceptor by use of metoprolol. Baseline HR (older vs. younger: 59 +/- 4 vs. 54 +/- 1 beats/min) and MAP (83 +/- 2 vs. 89 +/- 3 mmHg) were not significantly different between the groups. During -40 Torr, significant tachycardia occurred at the first HR response in the younger subjects without hypotension, whereas significant hypotension [change in MAP (DeltaMAP) -7 +/- 2 mmHg] was observed in the elderly without tachycardia. After the parasympathetic blockade, tachycardiac responses of younger subjects were diminished and associated with a significant hypotension at the onset of LBNP. However, MAP was not affected after the cardiac sympathetic blockade. We concluded that the elderly experienced orthostatic hypotension at the onset of orthostatic challenge because of a diminished HR response. However, an augmented vasoconstriction helped with the maintenance of their blood pressure during sustained LBNP.     

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.     

Effect of heat stress on cardiac output and systemic vascular conductance during simulated hemorrhage to presyncope in young men

During moderate actual or simulated hemorrhage, as cardiac output decreases, reductions in systemic vascular conductance (SVC) maintain mean arterial pressure (MAP). Heat stress, however, compromises the control of MAP during simulated hemorrhage, and it remains unknown whether this response is due to a persistently high SVC and/or a low cardiac output. This study tested the hypothesis that an inadequate decrease in SVC is the primary contributing mechanism by which heat stress compromises blood pressure control during simulated hemorrhage. Simulated hemorrhage was imposed via lower body negative pressure (LBNP) to presyncope in 11 passively heat-stressed subjects (increase core temperature: 1.2 ± 0.2°C; means ± SD). Cardiac output was measured via thermodilution, and SVC was calculated while subjects were normothermic, heat stressed, and throughout subsequent LBNP. MAP was not changed by heat stress but was reduced to 45 ± 12 mmHg at the termination of LBNP. Heat stress increased cardiac output from 7.1 ± 1.1 to 11.7 ± 2.2 l/min (P < 0.001) and increased SVC from 0.094 ± 0.018 to 0.163 ± 0.032 l·min(-1)·mmHg(-1) (P < 0.001). Although cardiac output at the onset of syncopal symptoms was 37 ± 16% lower relative to pre-LBNP, presyncope cardiac output (7.3 ± 2.0 l/min) was not different than normothermic values (P = 0.46). SVC did not change throughout LBNP (P > 0.05) and at presyncope was 0.168 ± 0.044 l·min(-1)·mmHg(-1). These data indicate that in humans a cardiac output adequate to maintain MAP while normothermic is no longer adequate during a heat-stressed-simulated hemorrhage. The absence of a decrease in SVC at a time of profound reductions in MAP suggests that inadequate control of vascular conductance is a primary mechanism compromising blood pressure control during these conditions.     

Validity of auscultatory and Penaz blood pressure measurements during profound heat stress alone and with an orthostatic challenge

Despite frequent reporting of blood pressure (BP) during profound passive heat stress, both with and without a hypotensive challenge, the method by which BP is measured often varies between laboratories. It is unknown whether auscultatory and finger BP measures accurately reflect intra-arterial BP during dynamic changes in cardiac output and peripheral resistance associated with the aforementioned conditions. The purpose of this investigation was to test the hypothesis that auscultatory BP measured at the brachial artery, and finger BP measured by the Penaz method, are valid measures of intra-arterial BP during a passive heat stress and a heat-stressed orthostatic challenge, via lower body negative pressure (LBNP). Absolute (specific aim 1) and the change in (specific aim 2) systolic (SBP), diastolic (DBP), and mean BPs (MBP) were compared at normothermia, after a core temperature increase of 1.47 ± 0.09°C, and during subsequent LBNP. Heat stress did not change auscultatory SBP (6 ± 11 mmHg; P = 0.16), but Penaz SBP (-22 ± 16 mmHg; P < 0.001) and intra-arterial SBP (-11 ± 13 mmHg P = 0.017) decreased. In contrast, DBP and MBP did not differ between methods throughout heat stress. Compared with BP before LBNP, the magnitude of the reduction in BP with all three methods was similar throughout LBNP (P > 0.05). In conclusion, auscultatory SBP and Penaz SBP failed to track the decrease in intra-arterial SBP that occurred during the profound heat stress, while decreases in arterial BP during an orthostatic challenge are comparable between methodologies.     

Cerebral autoregulation is preserved during orthostatic stress superimposed with systemic hypotension.

We sought to determine whether cerebral autoregulation (CA) is compromised during orthostatic stress superimposed with systemic hypotension. Transient systemic hypotension was produced by deflation of thigh cuffs previously inflated to suprasystolic pressure, combined with or without lower body negative pressure (LBNP). Cardiac output (CO) decreased from a baseline of 5.0+/-0.5 l/min by -8.3+/-1.7, -19.2+/-2.0, and -30.6+/-3.4% during LBNP of -15, -30, and -50 Torr, respectively. Mean arterial pressure (MAP) was maintained during LBNP, despite decreases in systolic and pulse pressures. Middle cerebral arterial blood flow velocity (VMCA) decreased significantly from a baseline of 64+/-3 to 58+/-4 cm/s (-9.7+/-2.4%) at -50 Torr of LBNP. The reduction in VMCA was associated with a decrease in regional cerebral O2 saturation. However, the percent decrease in VMCA was markedly less than that of CO. This suggests that the magnitude of the change in VMCA (an index of cerebral blood flow) is less than would be predicted, given the decrease in CO. Transient systemic hypotension decreased MAP by -21+/-2, -24+/-2, -28+/-3, and -26+/-3% at rest and during LBNP of -15, -30, and -50 Torr, respectively. Likewise, this acute hypotension resulted in decreases in VMCA of -20+/-2, -21+/-2, -24+/-25, and -19+/-2% and regional cerebral O2 saturation of -5+/-1, -6+/-1, -6+/-1, and -7+/-2% at rest and during LBNP of -15, -30, and -50 Torr, respectively. Complete recovery of VMCA to baseline values following transient hypotension (ranging from 5 to 8 s) occurred significantly earlier compared with MAP (from 10 to 12 s). No subjects experienced syncope during acute hypotension. We conclude that CA is preserved during LBNP, superimposed with transient systemic hypotension, despite the decrease in VMCA associated with sustained central hypovolemia in normal healthy individuals. This preserved CA is vital for the prevention of orthostatic syncope.     

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.     

Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety.

Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) without hypotension during orthostasis. The relationship between the tachycardia and anxiety is uncertain. Therefore, we tested whether the HR response to orthostatic stress in POTS is primarily related to psychological factors. POTS patients (n = 14) and healthy controls (n = 10) underwent graded venous pooling with lower body negative pressure (LBNP) to -40 mmHg while wearing deflated antishock trousers. "Sham" venous pooling was performed by 1) trouser inflation to 5 mmHg during LBNP and 2) vacuum pump activation without LBNP. HR responses to mental stress were also measured in both groups, and a questionnaire was used to measure psychological parameters. During LBNP, HR in POTS patients increased 39 +/- 5 beats/min vs. 19 +/- 3 beats/min in control subjects at -40 mmHg (P < 0.01). LBNP with trouser inflation markedly blunted the HR responses in the patients (9 +/- 2 beats/min) and controls (2 +/- 1 beats/min), and there was no HR increase during vacuum application without LBNP in either group. HR responses during mental stress were not different in the patients and controls (18 +/- 2 vs. 19 +/- 1 beats/min; P > 0.6). Anxiety, somatic vigilance, and catastrophic cognitions were significantly higher in the patients (P < 0.05), but they were not related to the HR responses during LBNP or mental stress (P > 0.1). These results suggest that the HR response to orthostatic stress in POTS patients is not caused by anxiety but that it is a physiological response that maintains arterial pressure during venous pooling.     

Modulation of control of muscle sympathetic nerve activity during orthostatic stress in humans

We tested the hypothesis that orthostatic stress would modulate the arterial baroreflex (ABR)-mediated beat-by-beat control of muscle sympathetic nerve activity (MSNA) in humans. In 12 healthy subjects, ABR control of MSNA (burst incidence, burst strength, and total activity) was evaluated by analysis of the relation between beat-by-beat spontaneous variations in diastolic blood pressure (DAP) and MSNA during supine rest (CON) and at two levels of lower body negative pressure (LBNP: -15 and -35 mmHg). At -15 mmHg LBNP, the relation between burst incidence (bursts per 100 heartbeats) and DAP showed an upward shift from that observed during CON, but the further shift seen at -35 mmHg LBNP was only marginal. The relation between burst strength and DAP was shifted upward at -15 mmHg LBNP (vs. CON) and further shifted upward at -35 mmHg LBNP. At -15 mmHg LBNP, the relation between total activity and DAP was shifted upward from that obtained during CON and further shifted upward at -35 mmHg LBNP. These results suggest that ABR control of MSNA is modulated during orthostatic stress and that the modulation is different between a mild (nonhypotensive) and a moderate (hypotensive) level of orthostatic stress.     

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.     

Skin surface cooling improves orthostatic tolerance in normothermic individuals

Previous studies suggest that skin surface cooling (SSC) preserves orthostatic tolerance; however, this hypothesis has not been experimentally tested. Thus the purpose of this project was to identify whether SSC improves orthostatic tolerance in otherwise normothermic individuals. Eight subjects underwent two presyncope limited graded lower-body negative pressure (LBNP) tolerance tests. On different days, and randomly assigned, LBNP tolerance was assessed under control conditions and during SSC (perfused 16 degrees C water through tube-lined suit worn by each subject). Orthostatic tolerance was significantly elevated in each individual due to SSC, as evidenced by a significant increase in a standardized cumulative stress index (normothermia 564 +/- 58 mmHg.min; SSC 752 +/- 58 mmHg.min; P < 0.05). At most levels of LBNP, blood pressure during the SSC tolerance test was significantly greater than during the control test. Furthermore, the reduction in cerebral blood flow velocity was attenuated during some of the early stages of LBNP for the SSC trial. Plasma norepinephrine concentrations were significantly higher during LBNP with SSC, suggesting that SSC may improve orthostatic tolerance through increased sympathetic activity. These data demonstrate that SSC is effective in improving orthostatic tolerance in otherwise normothermic individuals.     

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.     

Skin cooling maintains cerebral blood flow velocity and orthostatic tolerance during tilting in heated humans.

Orthostatic tolerance is reduced in the heat-stressed human. The purpose of this project was to identify whether skin-surface cooling improves orthostatic tolerance. Nine subjects were exposed to 10 min of 60 degrees head-up tilting in each of four conditions: normothermia (NT-tilt), heat stress (HT-tilt), normothermia plus skin-surface cooling 1 min before and throughout tilting (NT-tilt(cool)), and heat stress plus skin-surface cooling 1 min before and throughout tilting (HT-tilt(cool)). Heating and cooling were accomplished by perfusing 46 and 15 degrees C water, respectively, though a tube-lined suit worn by each subject. During HT-tilt, four of nine subjects developed presyncopal symptoms resulting in the termination of the tilt test. In contrast, no subject experienced presyncopal symptoms during NT-tilt, NT-tilt(cool), or HT-tilt(cool). During the HT-tilt procedure, mean arterial blood pressure (MAP) and cerebral blood flow velocity (CBFV) decreased. However, during HT-tilt(cool), MAP, total peripheral resistance, and CBFV were significantly greater relative to HT-tilt (all P < 0.01). No differences were observed in calculated cerebral vascular resistance between the four conditions. These data suggest that skin-surface cooling prevents the fall in CBFV during upright tilting and improves orthostatic tolerance, presumably via maintenance of MAP. Hence, skin-surface cooling may be a potent countermeasure to protect against orthostatic intolerance observed in heat-stressed humans.     

Effect of thermal stress on the vestibulosympathetic reflexes in humans.

Both heat stress and vestibular activation alter autonomic responses; however, the interaction of these two sympathetic activators is unknown. To determine the effect of heat stress on the vestibulosympathetic reflex, eight subjects performed static head-down rotation (HDR) during normothermia and whole body heating. Muscle sympathetic nerve activity (MSNA; peroneal microneurography), mean arterial blood pressure (MAP), heart rate (HR), and internal temperature were measured during the experimental trials. HDR during normothermia caused a significant increase in MSNA (Delta5 +/- 1 bursts/min; Delta53 +/- 14 arbitrary units/min), whereas no change was observed in MAP, HR, or internal temperature. Whole body heating significantly increased internal temperature (Delta0.9 +/- 0.1 degrees C), MSNA (Delta10 +/- 3 bursts/min; Delta152 +/- 44 arbitrary units/min), and HR (Delta25 +/- 6 beats/min), but it did not alter MAP. HDR during whole body heating increased MSNA (Delta16 +/- 4 bursts/min; Delta233 +/- 90 arbitrary units/min from normothermic baseline), which was not significantly different from the algebraic sum of HDR during normothermia and whole body heating (Delta15 +/- 4 bursts/min; Delta205 +/- 55 arbitrary units/min). These data suggest that heat stress does not modify the vestibulosympathetic reflex and that both the vestibulosympathetic and thermal reflexes are robust, independent sympathetic nervous system activators.     

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.