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.

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.

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.

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.

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.

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.).

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.

Cardiovascular function in the heat-stressed human.

Heat stress, whether passive (i.e. exposure to elevated environmental temperatures) or via exercise, results in pronounced cardiovascular adjustments that are necessary for adequate temperature regulation as well as perfusion of the exercising muscle, heart and brain. The available data suggest that generally during passive heat stress baroreflex control of heart rate and sympathetic nerve activity are unchanged, while baroreflex control of systemic vascular resistance may be impaired perhaps due to attenuated vasoconstrictor responsiveness of the cutaneous circulation. Heat stress improves left ventricular systolic function, evidenced by increased cardiac contractility, thereby maintaining stroke volume despite large reductions in ventricular filling pressures. Heat stress-induced reductions in cerebral perfusion likely contribute to the recognized effect of this thermal condition in reducing orthostatic tolerance, although the mechanism(s) by which this occurs is not completely understood. The combination of intense whole-body exercise and environmental heat stress or dehydration-induced hyperthermia results in significant cardiovascular strain prior to exhaustion, which is characterized by reductions in cardiac output, stroke volume, arterial pressure and blood flow to the brain, skin and exercising muscle. These alterations in cardiovascular function and regulation late in heat stress/dehydration exercise might involve the interplay of both local and central reflexes, the contribution of which is presently unresolved.

Early activation of the coagulation system during lower body negative pressure.

We considered that a moderate reduction of the central blood volume (CBV) may activate the coagulation system. Lower body negative pressure (LBNP) is a non-invasive means of reducing CBV and, thereby, simulates haemorrhage. We tested the hypothesis that coagulation markers would increase following moderate hypovolemia by exposing 10 healthy male volunteers to 10 min of 30 mmHg LBNP. Thoracic electrical impedance increased during LBNP (by 2.6 +/- 0.7 Omega, mean +/- SD; P < 0.001), signifying a reduced CBV. Heart rate was unchanged during LBNP, while mean arterial pressure decreased (84 +/- 5 to 80 +/- 6 mmHg; P < 0.001) along with stroke volume (114 +/- 22 to 96 +/- 19 ml min(-1); P < 0.001) and cardiac output (6.4 +/- 2.0 to 5.5 +/- 1.7 l min(-1); P < 0.01). Plasma thrombin-antithrombin III complexes increased (TAT, 5 +/- 6 to 19 +/- 20 microg l(-1); P < 0.05), indicating that LBNP activated the thrombin generating part of the coagulation system, while plasma D-dimer was unchanged, signifying that the increased thrombin generation did not cause further intravascular clot formation. The plasma pancreatic polypeptide level decreased (13 +/- 11 to 6 +/- 8 pmol l(-1); P < 0.05), reflecting reduced vagal activity. In conclusion, thrombin generation was activated by a modest decrease in CBV by LBNP in healthy humans independent of the vagal activity.

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 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.

Modeling Uhthoff's phenomenon in MS patients with internuclear ophthalmoparesis.

OBJECTIVE: The goal of this investigation was to demonstrate that internuclear ophthalmoparesis (INO) can be utilized to model the effects of body temperature-induced changes on the fidelity of axonal conduction in multiple sclerosis (Uhthoff's phenomenon). METHODS: Ocular motor function was measured using infrared oculography at 10-minute intervals in patients with multiple sclerosis (MS) with INO (MS-INO; n = 8), patients with MS without INO (MS-CON; n = 8), and matched healthy controls (CON; n = 8) at normothermic baseline, during whole-body heating (increase in core temperature 0.8 degrees C as measured by an ingestible temperature probe and transabdominal telemetry), and after whole-body cooling. The versional disconjugacy index (velocity-VDI), the ratio of abducting/adducting eye movements for velocity, was calculated to assess changes in interocular disconjugacy. The first pass amplitude (FPA), the position of the adducting eye when the abducting eye achieves a centrifugal fixation target, was also computed. RESULTS: Velocity-VDI and FPA in MS-INO patients was elevated (p < 0.001) following whole body heating with respect to baseline measures, confirming a compromise in axonal electrical impulse transmission properties. Velocity-VDI and FPA in MS-INO patients was then restored to baseline values following whole-body cooling, confirming the reversible and stereotyped nature of this characteristic feature of demyelination. CONCLUSIONS: We have developed a neurophysiologic model for objectively understanding temperature-related reversible changes in axonal conduction in multiple sclerosis. Our observations corroborate the hypothesis that changes in core body temperature (heating and cooling) are associated with stereotypic decay and restoration in axonal conduction mechanisms.

Effects of passive heating on central blood volume and ventricular dimensions in humans.

Mixed findings regarding the effects of whole-body heat stress on central blood volume have been reported. This study evaluated the hypothesis that heat stress reduces central blood volume and alters blood volume distribution. Ten healthy experimental and seven healthy time control (i.e. non-heat stressed) subjects participated in this protocol. Changes in regional blood volume during heat stress and time control were estimated using technetium-99m labelled autologous red blood cells and gamma camera imaging. Whole-body heating increased internal temperature (> 1.0 degrees C), cutaneous vascular conductance (approximately fivefold), and heart rate (52 +/- 2 to 93 +/- 4 beats min(-1)), while reducing central venous pressure (5.5 +/- 07 to 0.2 +/- 0.6 mmHg) accompanied by minor decreases in mean arterial pressure (all P < 0.05). The heat stress reduced the blood volume of the heart (18 +/- 2%), heart plus central vasculature (17 +/- 2%), thorax (14 +/- 2%), inferior vena cava (23 +/- 2%) and liver (23 +/- 2%) (all P

Effects of heat and cold stress on central vascular pressure relationships during orthostasis in humans.

Central venous pressure (CVP) provides information regarding right ventricular filling pressure, but is often assumed to reflect left ventricular filling pressure. It remains unknown whether this assumption is correct during thermal challenges when CVP is elevated during skin-surface cooling or reduced during whole-body heating. The primary objective of this study was to test the hypothesis that changes in CVP reflect those in left ventricular filling pressure, as expressed by pulmonary capillary wedge pressure (PCWP), during lower-body negative pressure (LBNP) while subjects are normothermic, during skin-surface cooling, and during whole-body heating. In 11 subjects, skin-surface cooling was imposed by perfusing 16 degrees C water through a water-perfused suit worn by each subject, while heat stress was imposed by perfusing 47 degrees C water through the suit sufficient to increase internal temperature 0.95 +/- 0.07 degrees C (mean +/- s.e.m.). While normothermic, CVP was 6.3 +/- 0.2 mmHg and PCWP was 9.5 +/- 0.3 mmHg. These pressures increased during skin-surface cooling (7.8 +/- 0.2 and 11.1 +/- 0.3 mmHg, respectively; P < 0.05) and decreased during whole-body heating (3.6 +/- 0.1 and 6.5 +/- 0.2 mmHg, respectively; P < 0.05). The decrease in CVP with LBNP was correlated with the reduction in PCWP during normothermia (r = 0.93), skin-surface cooling (r = 0.91), and whole-body heating (r = 0.81; all P < 0.001). When these three thermal conditions were combined, the overall r value between CVP and PCWP was 0.92. These data suggest that in the assessed thermal conditions, CVP appropriately tracks left ventricular filling pressure as indexed by PCWP. The correlation between these values provides confidence for the use of CVP in studies assessing ventricular preload during thermal and combined thermal and orthostatic perturbations.

Heat stress enhances arterial baroreflex control of muscle sympathetic nerve activity via increased sensitivity of burst gating, not burst area, in humans.

The relationship between muscle sympathetic nerve activity (MSNA) and diastolic blood pressure has been used to describe two sites for arterial baroreflex control of MSNA. By determining both the likelihood of occurrence for sympathetic bursts and the area of each burst for a given diastolic blood pressure, both a 'gating' and an 'area' control site has been described in normothermic humans. Assessing the effect of heat stress on these mechanisms will improve the understanding of baroreflex control of arterial blood pressure under this thermal condition. Therefore, the purpose of this study was to test the hypothesis that heat stress enhances arterial baroreflex control of burst gating and area. In 10 normotensive subjects (age, 32+/-2 years; mean+/-s.e.m.), MSNA (peroneal) was assessed using standard microneurographic techniques. Five minute periods of data were examined during normothermic and whole-body heating conditions. The burst incidence (i.e. number of sympathetic bursts per 100 cardiac cycles) and the area of each burst were determined for each cardiac cycle and were placed into 3 mmHg intervals of diastolic blood pressure. During normotheric conditions, there was a moderate, negative relationship between burst incidence and diastolic blood pressure (slope=-2.49+/-0.38; r(2)=0.73+/-0.06; mean+/-s.e.m.), while area per burst relative to diastolic blood pressure exhibited a less strong relationship (slope=-1.13+/-0.46; r(2)=0.45+/-0.09). During whole-body heating there was an increase in the slope of the relationship between burst incidence and diastolic blood pressure (slope=-4.69+/-0.44; r(2)=0.84+/-0.03) compared to normothermia (P<0.05), while the relationship between area per burst and diastolic blood pressure was unchanged (slope=-0.92+/-0.29; r(2)=0.41+/-0.08) (P=0.50). The primary finding of this investigation is that, at rest, whole-body heating enhanced arterial baroreflex control of MSNA through increased sensitivity of a 'gating' mechanism, as indicated by an increase in the slope of the relationship between burst incidence and diastolic blood pressure. This occurrence is likely to afford protection against potential decreases in arterial blood pressure in an effort to preserve orthostatic tolerance during heat stress.

Exogenous nitric oxide inhibits sympathetically mediated vasoconstriction in human skin.

Two experiments were performed to identify whether nitric oxide (NO) inhibits sympathetically mediated vasoconstriction in human skin. In eight subjects increasing doses of sodium nitroprusside (SNP; 8.4 x 10(-6)-8.4 x 10(-3)m) were administered via intradermal microdialysis. At each dose of SNP, cutaneous vasoconstrictor responsiveness was assessed during a 3 min whole-body cold stress. The relative reduction in forearm cutaneous vascular conductance (CVC) during the cold stress was significantly attenuated for SNP doses greater than 8.4 x 10(-4)m (control: 63.0 +/- 4.1%, SNP 8.4 x 10(-6)m: 57.1 +/- 4.7%, SNP 8.4 x 10(-5)m: 57.0 +/- 3.6%, SNP 8.4 x 10(-4)m: 44.5 +/- 5.4% and SNP 8.4 x 10(-3)m: 28.8 +/- 7.9%). The second experiment was performed to identify whether this response was due to NO attenuating sympathetically mediated vasoconstriction or due to a non-specific effect of an elevated CVC secondary to SNP administration. In seven subjects forearm CVC during a whole-body cold stress was assessed at two sites: at a site dilated via microdialysis administration of SNP and at a site dilated with isoproterenol (ISO). CVC was not different between sites prior to (SNP: 0.42 +/- 0.11; ISO: 0.46 +/- 0.11 AU mmHg(-1) (AU, arbitrary units), P > 0.05) or following drug infusion (SNP: 1.36 +/- 0.21; ISO: 1.27 +/- 0.23 AU mmHg(-1), P > 0.05). The reduction in CVC during the subsequent cold stress was significantly less at the SNP site (38.1 +/- 6.2%) relative to the ISO site (65.0 +/- 5.5%; P= 0.007). These data suggest NO is capable of inhibiting sympathetically mediated vasoconstriction in the cutaneous vasculature.

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 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.

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.

Sweating responses to a sustained static exercise is dependent on thermal load in humans.

The purpose of this project was to test the hypothesis that internal temperature modulates the sweating response to sustained handgrip exercise. Ten healthy male subjects immersed their legs in 43 degrees C water for 30-40 min at an ambient temperatures of 30 degrees C and a relative humidity of 50%. Sweating responses to 50% maximal voluntary contraction isometric handgrip exercise (IH) were measured following the onset of sweating (i.e. following slight increases in internal temperature), and after more pronounced increases in internal temperature. Oesophageal temperature (Tes) was significantly lower during the first bout of exercise (37.54 +/- 0.07 degrees C) relative to the second bout (37.84 +/- 0.12 degrees C; P < 0.05). However, the increase in mean sweating rate (SR) from both the chest and forearm (non-glabrous skin) was significantly greater during the first IH bout relative to the second bout (P < 0.05). Increases in mean arterial blood pressure and palm SR (glabrous skin) did not differ significantly between exercise bouts, while heart rate and rating of perceived effort were significantly greater during the second bout of IH. As Tes and mean skin temperature did not change during either bout of exercise, the changes in SR from non-glabrous skin between the bouts of IH were likely because of non-thermal factors. These data suggest that sweating responses from non-glabrous skin during IH vary depending on the magnitude of thermal input as indicated by differing internal temperatures between bouts of IH. Moreover, these data suggest that the contribution of non-thermal factors in governing sweating from non-glabrous skin may be greatest when internal temperature is moderate (37.54 degrees C), but has less of an effect after greater elevations in internal temperature (i.e. 37.84 degrees C).