Active and passive heat stress similarly compromise tolerance to a simulated hemorrhagic challenge.

Passive heat stress increases core and skin temperatures and reduces tolerance to simulated hemorrhage (lower body negative pressure; LBNP). We tested whether exercise-induced heat stress reduces LBNP tolerance to a greater extent relative to passive heat stress, when skin and core temperatures are similar. Eight participants (6 males, 32 ± 7 yr, 176 ± 8 cm, 77.0 ± 9.8 kg) underwent LBNP to presyncope on three separate and randomized occasions: 1) passive heat stress, 2) exercise in a hot environment (40°C) where skin temperature was moderate (36°C, active 36), and 3) exercise in a hot environment (40°C) where skin temperature was matched relative to that achieved during passive heat stress (∼38°C, active 38). LBNP tolerance was quantified using the cumulative stress index (CSI). Before LBNP, increases in core temperature from baseline were not different between trials (1.18 ± 0.20°C; P > 0.05). Also before LBNP, mean skin temperature was similar between passive heat stress (38.2 ± 0.5°C) and active 38 (38.2 ± 0.8°C; P = 0.90) trials, whereas it was reduced in the active 36 trial (36.6 ± 0.5°C; P ≤ 0.05 compared with passive heat stress and active 38). LBNP tolerance was not different between passive heat stress and active 38 trials (383 ± 223 and 322 ± 178 CSI, respectively; P = 0.12), but both were similarly reduced relative to active 36 (516 ± 147 CSI, both P ≤ 0.05). LBNP tolerance is not different between heat stresses induced either passively or by exercise in a hot environment when skin temperatures are similarly elevated. However, LBNP tolerance is influenced by the magnitude of the elevation in skin temperature following exercise induced heat stress.

Elevated local skin temperature impairs cutaneous vasoconstrictor responses to a simulated haemorrhagic challenge while heat stressed.

During a simulated haemorrhagic challenge, syncopal symptoms develop sooner when individuals are hyperthermic relative to normothermic. This is due, in part, to a large displacement of blood to the cutaneous circulation during hyperthermia, coupled with inadequate cutaneous vasoconstriction during the hypotensive challenge. The influence of local skin temperature on these cutaneous vasoconstrictor responses is unclear. This project tested the hypothesis that local skin temperature modulates cutaneous vasoconstriction during simulated haemorrhage in hyperthermic humans. Eight healthy participants (four men and four women; 32 ± 7 years old; 75.2 ± 10.8 kg) underwent lower-body negative pressure to presyncope while heat stressed via a water-perfused suit sufficiently to increase core temperature by 1.2 ± 0.2 °C. At forearm skin sites distal to the water-perfused suit, local skin temperature was either 35.2 ± 0.6 (mild heating) or 38.2 ± 0.2 °C (moderate heating) throughout heat stress and lower-body negative pressure, and remained at these temperatures until presyncope. The reduction in cutaneous vascular conductance during the final 90 s of lower-body negative pressure, relative to heat-stress baseline, was greatest at the mildly heated site (-10 ± 15% reduction) relative to the moderately heated site (-2 ± 12%; P = 0.05 for the magnitude of the reduction in cutaneous vascular conductance between sites), because vasoconstriction at the moderately heated site was either absent or negligible. In hyperthermic individuals, the extent of cutaneous vasoconstriction during a simulated haemorrhage can be modulated by local skin temperature. In situations where skin temperature is at least 38 °C, as is the case in soldiers operating in warm climatic conditions, a haemorrhagic insult is unlikely to be accompanied by cutaneous vasoconstriction.

Heat stress does not augment ventilatory responses to presyncopal limited lower body negative pressure.

Simulated haemorrhage, e.g. lower body negative pressure (LBNP), reduces central blood volume and mean arterial pressure, while ventilation increases. Passive whole-body heat stress likewise increases ventilation. The objective of this project was to test the hypothesis that ventilatory responses to reductions in central blood volume and arterial pressure during simulated haemorrhage are enhanced when individuals are heat stressed rather than normothermic. Eight healthy men (34 ± 9 years old, 176 ± 6 cm tall and 80.2 ± 4.2 kg body weight) underwent a simulated haemorrhagic challenge via LBNP until presyncope on two separate occasions, namely normothermic control and whole-body heat-stress trials. Baseline ventilation and core and mean skin temperatures were not different between trials (all P > 0.05). Prior to LBNP, heat stress increased core (from 36.8 ± 0.2 to 38.2 ± 0.2°C, P < 0.05) and mean skin temperatures (from 33.9 ± 0.5 to 38.1 ± 0.6°C, P < 0.05), as well as minute ventilation (from 8.01 ± 2.63 to 13.68 ± 6.68 l min(-1), P < 0.01). At presyncope, mean arterial pressure and middle cerebral artery blood velocity decreased in both trials (P < 0.05). At presyncope, ventilation increased to 23.22 ± 6.78 (P < 0.01) and 25.88 ± 10.16 l min(-1) (P < 0.01) in the normothermic and hyperthermic trials, respectively; however, neither the increase in ventilation from the pre-LBNP period nor the absolute ventilation was different between normothermic and hyperthermic trials (P > 0.05). These data suggest that the increase in ventilation during simulated haemorrhage induced via LBNP is not altered in heat-stressed humans.

Colloid volume loading does not mitigate decreases in central blood volume during simulated haemorrhage while heat stressed.

Heat stress results in profound reductions in the capacity to withstand a simulated haemorrhagic challenge; however, this capacity is normalized if the individual is volume loaded prior to the challenge. The present study tested the hypothesis that volume loading during passive heat stress attenuates the reduction in regional blood volumes during a simulated haemorrhagic challenge imposed via lower-body negative pressure (LBNP). Seven subjects underwent 30 mmHg LBNP while normothermic, during passive heat stress (increased internal temperature ∼1◦C), and while continuing to be heated after intravenous colloid volume loading (11 ml kg⁻¹). Relative changes in torso and regional blood volumes were determined by gamma camera imaging with technetium-99m labelled erythrocytes. Heat stress reduced blood volume in all regions (ranging from 7 to 16%), while subsequent volume loading returned those values to normothermic levels. While normothermic,LBNP reduced blood volume in all regions (torso: 22 ± 8%; heart: 18 ± 6%; spleen: 15 ± 8%). During LBNP while heat stressed, the reductions in blood volume in each region were markedly greater when compared to LBNP while normothermic (torso: 73 ± 2%; heart: 72 ± 3%; spleen: 72 ± 5%, all P<0.001 relative to normothermia). Volume loading during heat stress did not alter the extent of the reduction in these blood volumes to LBNP relative to heat stress alone (torso: 73 ± 1%; heart: 72 ± 2%; spleen: 74 ± 3%, all P>0.05 relative to heat stress alone). These data suggest that blood volume loading during passive heat stress (via 11 ml kg⁻¹ of a colloid solution) normalizes regional blood volumes in the torso, but does not mitigate the reduction in central blood volume during a simulated haemorrhagic challenge combined with heat stress.

Effect of volume loading on the Frank-Starling relation during reductions in central blood volume in heat-stressed humans.

During reductions in central blood volume while heat stressed, a greater decrease in stroke volume (SV) for a similar decrease in ventricular filling pressure, compared to normothermia, suggests that the heart is operating on a steeper portion of a Frank-Starling curve. If so, volume loading of heat-stressed individuals would shift the operating point to a flatter portion of the heat stress Frank-Starling curve thereby attenuating the reduction in SV during subsequent decreases in central blood volume. To investigate this hypothesis, right heart catheterization was performed in eight males from whom pulmonary capillary wedge pressure (PCWP), central venous pressure and SV (via thermodilution) were obtained while central blood volume was reduced via lower-body negative pressure (LBNP) during normothermia, whole-body heating (increase in blood temperature 1 degrees C), and during whole-body heating after intravascular volume expansion. Volume expansion was accomplished by administration of a combination of a synthetic colloid (HES 130/0.4, Voluven) and saline. Before LBNP, SV was not affected by heating (122 +/- 30 ml; mean +/- s.d.) compared to normothermia (110 +/- 20 ml; P = 0.06). However, subsequent volume loading increased SV to 143 +/- 29 ml (P = 0.003). LBNP provoked a larger decrease in SV relative to the decrease in PCWP during heating (8.6 +/- 1.9 ml mmHg(1)) compared to normothermia (4.5 +/- 3.0 ml mmHg(1), P = 0.02). After volume loading while heat stressed, the reduction in the SV to PCWP ratio during LBNP was comparable to that observed during normothermia (4.8 +/- 2.3 ml mmHg(1); P = 0.78). These data support the hypothesis that a Frank-Starling mechanism contributes to compromised blood pressure control during simulated haemorrhage in heat-stressed individuals, and extend those findings by showing that volume infusion corrects this deficit by shifting the operating point to a flatter portion of the heat stress Frank-Starling curve.

Insufficient cutaneous vasoconstriction leading up to and during syncopal symptoms in the heat stressed human.

As much as 50% of cardiac output can be distributed to the skin in the hyperthermic human, and therefore the control of cutaneous vascular conductance (CVC) becomes critical for the maintenance of blood pressure. Little is known regarding the magnitude of cutaneous vasoconstriction in profoundly hypotensive individuals while heat stressed. This project investigated the hypothesis that leading up to and during syncopal symptoms associated with combined heat and orthostatic stress, reductions in CVC are inadequate to prevent syncope. Using a retrospective study design, we evaluated data from subjects who experienced syncopal symptoms during lower body negative pressure (N = 41) and head-up tilt (N = 5). Subjects were instrumented for measures of internal temperature, forearm skin blood flow, arterial pressure, and heart rate. CVC was calculated as skin blood flow/mean arterial pressure × 100. Data were obtained while subjects were normothermic, immediately before an orthostatic challenge while heat stressed, and at 5-s averages for the 2 min preceding the cessation of the orthostatic challenge due to syncopal symptoms. Whole body heat stress increased internal temperature (1.25 ± 0.3°C; P < 0.001) and CVC (29 ± 20 to 160 ± 58 CVC units; P < 0.001) without altering mean arterial pressure (83 ± 7 to 82 ± 6 mmHg). Mean arterial pressure was reduced to 57 ± 9 mmHg (P < 0.001) immediately before the termination of the orthostatic challenge. At test termination, CVC decreased to 138 ± 61 CVC units (P < 0.001) relative to before the orthostatic challenge but remained approximately fourfold greater than when subjects were normothermic. This negligible reduction in CVC during pronounced hypotension likely contributes to reduced orthostatic tolerance in heat-stressed humans. Given that lower body negative pressure and head-up tilt are models of acute hemorrhage, these findings have important implications with respect to mechanisms of compromised blood pressure control in the hemorrhagic individual who is also hyperthermic (e.g., military personnel, firefighters, etc.).

Endothelial function in response to exercise in the cold in patients with coronary artery disease.

BACKGROUND: Regular long-term physical exercise has favourable effects on endothelial function in patients with coronary artery disease (CAD). However, the effects of an acute exercise bout in the cold on endothelial function are not known. METHODS: At first, the effects of moderate-intensity aerobic lower-body exercise were assessed in CAD patients (n = 16) in a neutral [+22°C] and cold [-15°C] environment. Secondly, responses to static and dynamic upper-body exercise in a neutral [+22°C] and cold [-15°C] environment were investigated in CAD patients (n = 15). All experiments were performed in a random order. Endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery in response to reactive hyperaemia, before and after the exposures in a neutral environment. RESULTS: No significant temperature*exercise*condition (pre-post) interaction was observed in FMD% when comparing rest versus aerobic exercise or static versus dynamic upper-body exercise. Relative reactive hyperaemia during FMD protocol, measured by changes in shear rate, was elevated after rest compared to aerobic exercise (p = .001) and after static compared to dynamic upper-body exercise (p < .001). However, no significant temperature*exercise*condition interaction was observed when FMD% was normalized for shear rate. CONCLUSIONS: Endothelial function to an acute bout of exercise among CAD patients was not modified by the environmental temperature where the exercise was performed. The present findings argue against the hypothesis that exercise in cold environmental conditions impairs endothelial function in patients with CAD.

Effect of thermal stress on Frank-Starling relations in humans.

The Frank-Starling 'law of the heart' is implicated in certain types of orthostatic intolerance in humans. Environmental conditions have the capacity to modulate orthostatic tolerance, where heat stress decreases and cooling increases orthostatic tolerance. The objective of this project was to test the hypothesis that heat stress augments and cooling attenuates orthostatic-induced decreases in stroke volume (SV) via altering the operating position on a Frank-Starling curve. Pulmonary artery catheters were placed in 11 subjects for measures of pulmonary capillary wedge pressure (PCWP) and SV (thermodilution derived cardiac output/heart rate). Subjects experienced lower-body negative-pressure (LBNP) of 0, 15 and 30 mmHg during normothermia, skin-surface cooling (decrease in mean skin temperature of 4.3 +/- 0.4 degrees C (mean +/- s.e.m.) via perfusing 16 degrees C water through a tubed-lined suit), and whole-body heating (increase in blood temperature of 1.0 +/- 0.1 degrees C via perfusing 46 degrees C water through the suit). SV was 123 +/- 8, 121 +/- 10, 131 +/- 7 ml prior to LBNP, during normothermia, skin-surface cooling, and whole-body heating, respectfully (P = 0.20). LBNP of 30 mmHg induced greater decreases in SV during heating (-48.7 +/- 6.7 ml) compared to normothermia (-33.2 +/- 7.4 ml) and to cooling (-10.3 +/- 2.9 ml; all P < 0.05). Relating PCWP to SV indicated that cooling values were located on the flatter portion of a Frank-Starling curve because of attenuated decreases in SV per decrease in PCWP. In contrast, heating values were located on the steeper portion of a Frank-Starling curve because of augmented decreases in SV per decrease in PCWP. These data suggest that a Frank-Starling mechanism may contribute to improvements in orthostatic tolerance during cold stress and orthostatic intolerance during heat stress.

Botulinum toxin abolishes sweating via impaired sweat gland responsiveness to exogenous acetylcholine.

BACKGROUND: Botulinum toxin A (BTX) disrupts neurotransmitter release from cholinergic nerves. The effective duration of impaired sweat secretion with BTX is longer relative to that of impaired muscle contraction, suggesting different mechanisms in these tissues. OBJECTIVES: The aim of this study was to test the hypothesis that BTX is capable of altering sweating by reducing the responsiveness of the sweat gland to acetylcholine. METHODS: BTX was injected into the dorsal forearm skin of healthy subjects at least 3 days before subsequent assessment. On the day of the experiment, intradermal microdialysis probes were placed within the BTX-treated area and in an adjacent untreated area. Incremental doses of acetylcholine were administered through the microdialysis membranes while the sweat rate (protocol 1; n = 8) or a combination of sweat rate and skin blood flow (protocol 2; n = 8) were assessed. RESULTS: A relative absence of sweating was observed at the BTX site for both protocols (protocol 1: 0.05 +/- 0.09 mg cm(-2) min(-1); protocol 2: 0.03 +/- 0.04 mg cm(-2) min(-1), both at the highest dose of acetylcholine), while the sweat rate increased appropriately at the control sites (protocol 1: 0.90 +/- 0.46 mg cm(-2) min(-1); protocol 2: 1.07 +/- 0.67 mg cm(-2) min(-1)). Cutaneous vascular conductance increased to a similar level at both the BTX and control sites. CONCLUSIONS: These results demonstrate that BTX is capable of inhibiting sweat secretion by reducing the responsiveness of the sweat gland to acetylcholine, while not altering acetylcholine-mediated cutaneous vasodilatation.

Effect of local acetylcholinesterase inhibition on sweat rate in humans.

ACh is the neurotransmitter responsible for increasing sweat rate (SR) in humans. Because ACh is rapidly hydrolyzed by acetylcholinesterase (AChE), it is possible that AChE contributes to the modulation of SR. Thus the primary purpose of this project was to identify whether AChE around human sweat glands is capable of modulating SR during local application of various concentrations of ACh in vivo, as well as during a heat stress. In seven subjects, two microdialysis probes were placed in the intradermal space of the forearm. One probe was perfused with the AChE inhibitor neostigmine (10 microM); the adjacent membrane was perfused with the vehicle (Ringer solution). SR over both membranes was monitored via capacitance hygrometry during microdialysis administration of various concentrations of ACh (1 x 10(-7)-2 M) and during whole body heating. SR was significantly greater at the neostigmine-treated site than at the control site during administration of lower concentrations of ACh (1 x 10(-7)-1 x 10(-3) M, P < 0.05), but not during administration of higher concentrations of ACh (1 x 10(-2)-2 M, P > 0.05). Moreover, the core temperature threshold for the onset of sweating at the neostigmine-treated site was significantly reduced relative to that at the control site. However, no differences in SR were observed between sites after 35 min of whole body heating. These results suggest that AChE is capable of modulating SR when ACh concentrations are low to moderate (i.e., when sudomotor activity is low) but is less effective in governing SR after SR has increased substantially.

Cutaneous interstitial nitric oxide concentration does not increase during heat stress in humans.

Inhibition of cutaneous nitric oxide (NO) synthase reduces the magnitude of cutaneous vasodilation during whole body heating in humans. However, this observation is insufficient to conclude that NO concentration increases in the skin during a heat stress. This study was designed to test the hypothesis that whole body heating increases cutaneous interstitial NO concentration. This was accomplished by placing 2 microdialysis membranes in the forearm dermal space of 12 subjects. Both membranes were perfused with lactated Ringer solutions at a rate of 2 microl/min. In both normothermia and during whole body heating via a water perfused suit, dialysate from these membranes were obtained and analyzed for NO using the chemiluminescence technique. In six of these subjects, after the heat stress, the membranes were perfused with a 1 M solution of acetylcholine to stimulate NO release. Dialysate from these trials was also assayed to quantify cutaneous interstitial NO concentration. Whole body heating increased skin temperature from 34.6 +/- 0.2 to 38.8 +/- 0.2 degrees C (P < 0.05), which increased sublingual temperature (36.4 +/- 0.1 to 37.6 +/- 0.1 degrees C; P < 0.05), heart rate (63 +/- 5 to 93 +/- 5 beats/min; P < 0.05), and skin blood flow over the membranes (21 +/- 4 to 88 +/- 10 perfusion units; P < 0.05). NO concentration in the dialysate did not increase significantly during of the heat stress (7.6 +/- 0.7 to 8.6 +/- 0.8 microM; P > 0.05). After the heat stress, administration of acetylcholine in the perfusate significantly increased skin blood flow (128 +/- 6 perfusion units) relative to both normothermic and heat stress values and significantly increased NO concentration in the dialysate (15.8 +/- 2.4 microM). These data suggest that whole body heating does not increase cutaneous interstitial NO concentration in forearm skin. Rather, NO may serve in a permissive role in facilitating the effects of an unknown neurotransmitter, leading to cutaneous vasodilation during a heat stress.

Effect of increasing central venous pressure during passive heating on skin blood flow.

Whole body heating in humans increases skin blood flow (SkBF) and decreases central venous pressure (CVP). This study sought to identify whether elevations in SkBF are augmented during passive heating if CVP is increased during the heat stress. Seven subjects were exposed to passive heating. Once SkBF was substantially elevated, 15 ml/kg warm saline were rapidly infused intravenously. Whole body heating significantly increased cutaneous vascular conductance and decreased CVP from 7.7 +/- 0.6 to 4.9 +/- 0.5 mmHg (P < 0.05). Saline infusion returned CVP to pre-heat-stress pressures (7.9 +/- 0.6 mmHg; P > 0.05) and significantly increased cutaneous vascular conductance relative to the period before saline administration. Moreover, saline infusion did not alter mean arterial pressure, pulse pressure, or esophageal temperature (all P > 0.05). To serve as a volume control, 15 ml/kg saline were rapidly infused intravenously in normothermic subjects. Saline infusion increased CVP (P < 0.05) without affecting mean arterial pressure, pulse pressure, or cutaneous vascular conductance (all P > 0.05). These data suggest that cardiopulmonary baroreceptor unloading during passive heating may attenuate the elevation in SkBF in humans, whereas loading cardiopulmonary baroreceptors in normothermia has no effect on SkBF.

Evidence of a myogenic response in vasomotor control of forearm and palm cutaneous microcirculations.

Previous investigations of autoregulatory mechanisms in the control of skin blood flow suffer from the possibility of interfering effects of the autonomic nervous system. To address this question, in 11 subjects cutaneous vascular responses were measured during acute changes in perfusion pressure (using Valsalva maneuver; VM) before and after ganglionic blockade via systemic trimethaphan infusion. Cutaneous vascular conductance at baseline (CVC(base)) and during the last 5 s of the VM (CVC(VM)) were measured from forearm (nonglabrous) and palm (glabrous) skin. During the VM without ganglionic blockade, compared with CVC(base), CVC(VM) decreased significantly at the palm [0.79 +/- 0.17 to 0.55 +/- 0.17 arbitrary units (AU)/mmHg; P = 0.002] but was unchanged at the forearm (0.13 +/- 0.02 to 0.16 +/- 0.02 AU/mmHg; P = 0.50). After ganglionic blockade, VM induced pronounced decreases in perfusion pressure, which resulted in significant increases in CVC(VM) at both forearm (0.19 +/- 0.03 to 0.31 +/- 0.07 AU/mmHg; P = 0.008) and palm (1.84 +/- 0.29 to 2.76 +/- 0.63 AU/mmHg; P = 0.003) sites. These results suggest that, devoid of autonomic control, both glabrous and nonglabrous skin are capable of exhibiting vasomotor autoregulation during pronounced reductions in perfusion pressure.

Skin of the dorsal aspect of human hands and fingers possesses an active vasodilator system.

To test for an active vasodilator system in human hand and finger skin, seven subjects had a small area of dorsal hand, palm, or dorsal finger pretreated with bretylium (BT) to block adrenergic vasoconstriction. Skin blood flow was monitored at a BT-treated site, a comparable untreated site, and the forearm by laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was evaluated from the ratio of blood flow to arterial pressure. Body cooling, to evaluate vasoconstrictor system blockade, caused CVC at untreated sites of forearm, palm, dorsal hand, and dorsal finger to fall by 45 +/- 4, 85 +/- 5, 51 +/- 9, and 63 +/- 7%, respectively (all P < 0.05). At BT-treated sites of palm, dorsal hand, and dorsal finger, reductions in CVC were only 13 +/- 3, 2 +/- 18, and 13 +/- 4%, respectively (dorsal hand not significant, others P < 0.05). With body heating, increases in CVC at untreated sites of forearm, palm, dorsal hand, and dorsal finger were 881 +/- 165, 779 +/- 368, 423 +/- 115, and 1,430 +/- 716%, respectively (all P < 0.05). At BT-treated sites of palm, dorsal hand, and dorsal finger, increases were 35 +/- 15, 342 +/- 107, and 343 +/- 34%, respectively (palm not significant, others P < 0.05). Increased CVC at the palm began after 1.2 +/- 0.2 min of heating, significantly earlier than forearm (11.8 +/- 2.5 min), dorsal hand (16.4 +/- 3.4 min), or dorsal finger (15.6 +/- 3.6 min), which did not differ significantly from one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Function of human eccrine sweat glands during dynamic exercise and passive heat stress.

The purpose of this study was to identify the pattern of change in the density of activated sweat glands (ASG) and sweat output per gland (SGO) during dynamic constant-workload exercise and passive heat stress. Eight male subjects (22.8 +/- 0.9 yr) exercised at a constant workload (117.5 +/- 4.8 W) and were also passively heated by lower-leg immersion into hot water of 42 degrees C under an ambient temperature of 25 degrees C and relative humidity of 50%. Esophageal temperature, mean skin temperature, sweating rate (SR), and heart rate were measured continuously during both trials. The number of ASG was determined every 4 min after the onset of sweating, whereas SGO was calculated by dividing SR by ASG. During both exercise and passive heating, SR increased abruptly during the first 8 min after onset of sweating, followed by a slower increase. Similarly for both protocols, the number of ASG increased rapidly during the first 8 min after the onset of sweating and then ceased to increase further (P > 0.05). Conversely, SGO increased linearly throughout both perturbations. Our results suggest that changes in forearm sweating rate rely on both ASG and SGO during the initial period of exercise and passive heating, whereas further increases in SR are dependent on increases in SGO.

Cutaneous vascular and sudomotor responses to isometric exercise in humans.

To identify whether isometric handgrip exercise (IHG) affects cutaneous vasoconstrictor and/or active vasodilator activities, seven subjects (6 men and 1 woman) performed 30% maximal voluntary contraction of a forearm under normothermic (1 bout) and hyperthermic (2 bouts) conditions. Skin blood flow was indexed by laser-Doppler flowmetry at a contralateral forearm site at which adrenergic vasoconstrictor function was blocked by iontophoresis of bretylium tosylate (BT) and therefore only has active vasodilation as a mechanism for reflex control. Skin blood flow was also monitored at an adjacent untreated site. Cutaneous vascular conductance (CVC) was calculated from the flow signal and noninvasive blood pressure. CVC was normalized to the value obtained from maximal vasodilation at that site. Sweat rate (SR) was measured at the same locations. During normothermia, IHG did not affect CVC at the control or BT-treated sites, nor did IHG affect SR (P > 0.05). The second bout of IHG in hyperthermia evoked significant reductions in CVC at the untreated (69.4 +/- 3.4 to 58.9 +/- 2.5% of maximum, P < 0.05) and BT-treated sites (75.4 +/- 6.1 to 64.4 +/- 6.2% of maximum, P < 0.05), whereas SR significantly increased (0.62 +/- 0.16 to 0.70 +/- 0.17 mg.cm-2.min-1, P < 0.05). These findings uniquely show that, in hyperthermia, IHG reduces active vasodilator activity while at the same time sudomotor activity is increasing. This suggests independent control of these effectors.

Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans.

Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.

Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans.

To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.001) during posthandgrip muscle ischemia (-201.9 +/- 20.4 units. beat(-1). mmHg(-1)) when compared with control conditions (-142.7 +/- 17.3 units. beat(-1). mmHg(-1)). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.

Aortic baroreflex control of heart rate after 15 days of simulated microgravity exposure.

To determine the effects of simulated microgravity on aortic baroreflex control of heart rate, we exposed seven male subjects (mean age 38 +/- 3 yr) to 15 days of bed rest in the 6 degrees head-down position. The sensitivity of the aortic-cardiac baroreflex was determined during a steady-state phenylephrine-induced increase in mean arterial pressure combined with lower body negative pressure to counteract central venous pressure increases and neck pressure to offset the increased carotid sinus transmural pressure. The aortic-cardiac baroreflex gain was assessed by determining the ratio of the change in heart rate to the change in mean arterial pressure between baseline conditions and aortic baroreceptor-isolated conditions (i.e., phenylephrine + lower body negative pressure + neck pressure stage). Fifteen days of head-down tilt increased the gain of the aortic-cardiac baroreflex (from 0.45 +/- 0.07 to 0.84 +/- 0.18 beats.min-1.mmHg-1; P = 0.03). Reductions in blood volume and/or maximal aerobic capacity may represent the underlying mechanism(s) responsible for increased aortic baroreflex responsiveness after exposure to a ground-based analogue of microgravity.

Altered thermoregulatory responses after 15 days of head-down tilt.

To determine whether extended exposure to a simulation of microgravity alters thermoregulatory reflex control of skin blood flow, six adult males (mean age 40 +/- 2 yr) were exposed to 15 days of 6 degrees head-down tilt (HDT). On an ambulatory control day before HDT exposure and on HDT day 15, the core temperature of each subject was increased by 0.5-1.0 degree C by whole body heating with a water-perfused suit. Mean skin temperature, oral temperature (Tor), mean arterial pressure, and forearm blood flow were measured throughout the protocol. Forearm vascular conductance (FVC) was calculated from the ratio of forearm blood flow to mean arterial pressure. After HDT exposure, the Tor threshold at which reflex thermally induced increases in FVC began was elevated (36.87 +/- 0.06 to 37.00 +/- 0.09 degrees C; P = 0.043), whereas the slope of the Tor-FVC relationship after this threshold was reduced (13.7 +/- 2.3 to 9.5 +/- 1.1 FVC units/degrees C; P = 0.038). Moreover, normothermic FVC and FVC at the highest common Tor between pre- and post-HDT trials were reduced after HDT (normothermic: 4.2 +/- 0.5 to 3.0 +/- 0.4 ml.100 ml-1.min-1.100 mmHg-1, P = 0.04; hyperthermic: 12.4 +/- 1.0 to 7.8 +/- 0.7 ml.100 ml-1.min-1.100 mmHg-1, P < 0.001). These data suggest that HDT exposure reduces thermoregulatory responses to heat stress. The mechanisms resulting in such an impaired thermoregulatory response are unknown but are likely related to the relative dehydration that accompanies this exposure.