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Previously, we found that nitric oxide (NO) inhibits cutaneous vasoconstrictor responsiveness evoked by whole body cooling, as well as an orthostatic stress in the heat-stressed human (Shibasaki M, Durand S, Davis SL, Cui J, Low DA, Keller DM, Crandall CG. J Physiol 585: 627–634, 2007). However, it remains unknown whether this response occurs via NO acting through presynaptic or postsynaptic mechanisms. The aim of this study was to test the hypothesis that NO is capable of impairing cutaneous vasoconstriction via postsynaptic mechanisms. Skin blood flow was monitored over two forearm sites where intradermal microdialysis membranes were previously placed. Skin blood flow was elevated four- to fivefold through perfusion of the NO donor sodium nitroprusside at one site and through perfusion of adenosine (primarily non-NO mechanisms) at a second site. Once a plateau in vasodilation was evident, increasing concentrations of norepinephrine (1 × 10−8 to 1 × 10−2 M) were administrated through both microdialysis probes, while the aforementioned vasodilator agents continued to be perfused. Cutaneous vascular conductance was calculated by dividing skin blood flow by mean arterial blood pressure. The administration of norepinephrine decreased cutaneous vascular conductance at both sites. However, the dose of norepinephrine at the onset of vasoconstriction (−5.9 ± 1.3 vs. −7.2 ± 0.7 log M norepinephrine, P = 0.021) and the concentration of norepinephrine resulting in 50% of the maximal vasoconstrictor response (−4.9 ± 1.2 vs. −6.1 ± 0.2 log M norepinephrine dose; P = 0.012) occurred at significantly higher norepinephrine concentrations for the sodium nitroprusside site relative to the adenosine site, respectively. These results suggested that NO is capable of attenuating cutaneous vasoconstrictor responsiveness to norepinephrine via postsynaptic mechanisms.

OBJECTIVE The aim of this study was to test the hypothesis that the postmenopausal hot flash is accompanied by rapid decreases in arterial blood pressure and increases in cutaneous vascular conductance (CVC), as evaluated by continuous measurements of these variables in symptomatic women. DESIGN Twelve healthy, normotensive, postmenopausal women rested in a temperature-controlled laboratory (26 degrees C) for approximately 90 minutes. The onset of a hot flash was objectively identified as a transient and pronounced elevation of sternal sweat rate (capacitance hygrometry). RESULTS Twenty-three hot flashes were recorded during the experimental sessions (3.4 +/- 1.4 min; range, 1.3-6.5 min). Mean arterial blood pressure decreased 13 +/- 2 mm Hg during 11 hot flashes in five participants. Data from these participants, categorized as responders, were analyzed separately from data for those participants whose blood pressure did not change during their hot flashes (n = 7, 12 hot flashes). Heart rate (obtained from an electrocardiogram) significantly increased during the hot flashes, but there was no difference between the responder and nonresponder groups (9 +/- 2 vs 10 +/- 1 beats/min, respectively; P > 0.05). The increase in CVC was not different between groups at either the forearm (15% +/- 3% vs 12% +/- 3% maximal CVC, P > 0.05) or sternum (24% +/- 5% vs 21% +/- 3% maximal CVC, P > 0.05). CONCLUSIONS These data demonstrate that in a subset of participants, the hot flash is accompanied by a significant reduction in blood pressure, but there is no difference in CVC between these women and women with no drop in blood pressure.

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).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.Velocity-VDI and FPA in MS-INO patients was elevated (p0.001) 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.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.

Exercise in the heat can pose a severe challenge to human cardiovascular control, and thus the provision of oxygen to exercising muscles and vital organs, because of enhanced thermoregulatory demand for skin blood flow coupled with dehydration and hyperthermia. Cardiovascular strain, typified by reductions in cardiac output, skin and locomotor muscle blood flow and systemic and muscle oxygen delivery accompanies marked dehydration and hyperthermia during prolonged and intense exercise characteristic of many summer Olympic events. This review focuses on how the cardiovascular system is regulated when exercising in the heat and how restrictions in locomotor skeletal muscle and/or skin perfusion might limit athletic performance in hot environments.

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

Cutaneous vasoconstrictor responsiveness may be impaired by substance(s) directly or indirectly responsible for cutaneous active vasodilatation. In this study, we tested the hypothesis that endogenous nitric oxide (NO) attenuates the reduction in cutaneous vascular conductance (CVC) during an orthostatic challenge combined with whole-body heating, as well as during whole-body cooling. In protocol 1, healthy subjects were pretreated with an intradermal injection of botulinum toxin A (BTX) to block the release of neurotransmitters from nerves responsible for cutaneous active vasodilatation. On the experimental day, a microdialysis probe was placed at the BTX-treated site as well as at two adjacent untreated sites. NG-nitro-l-arginine methyl ester (l-NAME, 10 mm) was perfused through the probe placed at the BTX-treated site and at one untreated site. After confirmation of the absence of cutaneous vasodilatation at the BTX site during whole-body heating, adenosine was infused through the microdialysis probe at this site to increase skin blood flow to a level similar to that at the untreated site. Subsequently, 30 and 40 mmHg lower-body negative pressures (LBNPs) were applied. The reduction in CVC to LBNP was greatest at the BTX-treated site (15.0 ± 2.4% of the maximum level (% max)), followed by the l-NAME-treated site (11.3 ± 2.6% max), and then the untreated site (3.8 ± 3.0% max; P < 0.05 for all comparisons). In protocol 2, two microdialysis membranes were inserted in the dermal space of one forearm. Adenosine alone was infused at one site while the other site received adenosine and l-NAME. The reduction in CVC in response to whole-body cooling was significantly greater at the l-NAME-treated site than at the adjacent adenosine alone site. These results suggest that endogenous NO is capable of attenuating cutaneous vasoconstrictor responsiveness.

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.

The aim of this study was to assess the accuracy of temporal scanning thermometry in monitoring internal temperature increases during passive heating.Sixteen subjects (5 males and 11 females) underwent a whole-body passive heat stress (water-perfused suit) to increase internal temperature. Temperatures were obtained with a temporal scanner and with an ingestible-pill telemetry system that tracks intestinal temperature. Temperatures were recorded while subjects were normothermic (34 degrees C water-perfusing suit) and every 10 min during passive heating (48 degrees C water-perfusing suit).Heart rate (ECG), mean skin temperature (weighted six-site average), skin blood flow (laser Doppler flowmetry), and sweat rate (capacitance hygrometry) were all significantly elevated at the end of heating (all P0.001). Pre-heat stress temporal-derived temperature was not different from intestinal temperature (36.98 +/- 0.09 vs 37.01 +/- 0.09 degrees C, respectively, P = 0.76). However, after 30 min of heating (the greatest duration of heating completed by all subjects), temporal-derived temperature decreased to below the pre-heat stress baseline (-0.22 +/- 0.11), whereas intestinal temperature increased by 0.39 +/- 0.07 degrees C (P0.001 between the two methods). After 50 min of heating (N = 11), intestinal-derived internal temperature increased by 0.70 +/- 0.09 degrees C, whereas temporal-derived temperature decreased by 0.29 +/- 0.10 degrees C (P0.001). The group average (+/- SEM) R2 and slope between the two methods were 0.29 +/- 0.08 and -0.34 +/- 0.14, respectively.These results demonstrate that temporal scanning does not track internal temperature, as measured via intestinal temperature, during passive heating. Given these findings, it is recommended that this technique not be used to assess temperature in hyperthermic diaphoretic subjects.

The aim of this investigation was to identify the consequences of skin grafting on cutaneous vasodilation and sweating in split-thickness grafted skin during indirect whole-body heating 5 to 9 months after surgery. In addition, thermoregulatory function was examined at donor skin sites on a separate day. Skin blood flow and sweat rate (SR) were assessed from both grafted (n = 14) or donor skin (n = 11) and compared with the respective adjacent control skin during indirect whole-body heating. Cutaneous vascular conductance (CVC) was calculated from the ratio of skin blood flow (arbitrary units; au) to mean arterial pressure. Whole-body heating significantly increased internal temperature (37.0 +/- 0.1 degrees C to 37.8 +/- 0.1 degrees C; P < .05). Cutaneous vasodilation (ie, the increase in CVC from baseline, deltaCVC) during whole-body heating was significantly attenuated in grafted skin (deltaCVC = 0.14 +/- 0.15 au/mm Hg) compared with adjacent control skin (deltaCVC = 0.84 +/- 0.11 au/mm Hg; P < .05). Increases in sweat rate (deltaSR) were also significantly lower in grafted skin (deltaSR = 0.08 +/- 0.08 mg/cm2/min) compared with adjacent control skin (deltaSR = 1.16 +/- 0.20 mg/ cm2/min; P < .05). Cutaneous vasodilation and sweating during heating were not significantly different between donor sites (deltaCVC = 0.71 +/- 0.19 au/mm Hg; deltaSR = 1.04 +/- 0.15 mg/cm2/min) and adjacent control skin (deltaCVC = 0.50 +/- 0.10 au/mm Hg; deltaSR = 0.83 +/- 0.17 mg/cm2/min). Greatly attenuated or absence of cutaneous vasodilation and sweating suggests impairment of thermoregulatory function in grafted skin, thereby, diminishing the contribution of this skin to overall temperature control during a heat stress.

OBJECTIVE: To counteract long-lasting muscle break down, muscle weakness, and poor physical fitness resulting from severe burns, we recommend a 12-week in-hospital exercise training rehabilitation program. Unfortunately, this in-hospital training program requires time away from home, family, school or work. This study was undertaken to evaluate an alternative exercise rehabilitation strategy involving a 12-week community-based exercise training rehabilitation program (COMBEX) carried out at or near the patient and caretaker's home. STUDY DESIGN AND PARTICIPANTS: Pediatric patients (7-18 years) with ≥30% of total body surface area (TBSA) burns were randomized to participate in COMBEX (N=12) or an outpatient exercise program (EX) at the hospital (N=22). Both programs were started after hospital discharge and consisted of 12 weeks of progressive resistive and aerobic exercise. COMBEX was performed in community fitness centers near the patients' home. Endpoints were assessed at discharge (pre-exercise) and after the 12-week program. Primary endpoints were lean body mass (dual energy X-ray absorptiometry), muscle strength (isokinetic dynamometry), and peak aerobic capacity (indirect calorimetry). RESULTS: Demographics, length of hospitalization, and TBSA burned were comparable between groups (P>0.05). Both groups exhibited a significant (P≤0.01 for all) increase (mean±SEM) in lean muscle mass (EX: 6.9±1.7%; COMBEX: 6.5±1.1%), muscle strength (EX: 67.1±7.0%; COMBEX: 49.9±6.8%), and peak aerobic capacity (EX: 35.5±4.0%; COMBEX: 46.9±7.7%). Furthermore, the magnitude of these increases were not different between groups (P>0.12). CONCLUSIONS: Both EX and COMBEX are efficacious in improving lean mass, strength, and cardiopulmonary capacity in severely burned children. Language: en

This study aims to evaluate the effect of regular post-exercise cold water immersion (CWI) on intramuscular markers of cellular stress response and signaling molecules related to mitochondria biogenesis and exercise performance after 4 weeks of high intensity interval training (HIIT). Seventeen healthy subjects were allocated into two groups: control (CON, n = 9) or CWI (n = 8). Each HIIT session consisted of 8–12 cycling exercise stimuli (90–110 % of peak power) for 60 s followed by 75 s of active recovery three times per week, for 4 weeks (12 HIIT sessions). After each HIIT session, the CWI had their lower limbs immersed in cold water (10 °C) for 15 min and the CON recovered at room temperature. Exercise performance was evaluated before and after HIIT by a 15-km cycling time trial. Vastus lateralis biopsies were obtained pre and 72 h post training. Samples were analyzed for heat shock protein 72 kDa (Hsp72), adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) assessed by western blot. In addition, the mRNA expression of heat shock factor-1 (HSF-1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 1 and 2 (NRF1 and 2), mitochondrial transcription factor A (Tfam), calcium calmodulin-dependent protein kinase 2 (CaMK2) and enzymes citrate synthase (CS), carnitine palmitoyltransferase I (CPT1), and pyruvate dehydrogenase kinase (PDK4) were assessed by real-time PCR. Time to complete the 15-km cycling time trial was reduced with training (p 0.05). No differences were observed with training or condition for mRNA expression of PGC-1α (p = 0.31), CPT1 (p = 0.14), CS (p = 0.44), and NRF-2 (p = 0.82). However, HFS-1 (p = 0.007), PDK4 (p = 0.03), and Tfam (p = 0.03) mRNA were higher in CWI. NRF-1 decrease in both groups after training (p = 0.006). CaMK2 decreased with HIIT (p = 0.003) but it was not affected by CWI (p = 0.99). Cold water immersion does not alter HIIT-induced Hsp72, AMPK, p38 MAPK, and exercise performance but was able to increase some markers of cellular stress response and signaling molecules related to mitochondria biogenesis.

Heat stress profoundly and unanimously reduces orthostatic tolerance. This review aims to provide an overview of the numerous and multifactorial mechanisms by which this occurs in humans. Potential causal factors include changes in arterial and venous vascular resistance and blood distribution, and the modulation of cardiac output, all of which contribute to the inability to maintain cerebral perfusion during heat and orthostatic stress. A number of countermeasures have been established to improve orthostatic tolerance during heat stress, which alleviate heat stress induced central hypovolemia (e.g., volume expansion) and/or increase peripheral vascular resistance (e.g., skin cooling). Unfortunately, these countermeasures can often be cumbersome to use with populations prone to syncopal episodes. Identifying the mechanisms of inter-individual differences in orthostatic intolerance during heat stress has proven elusive, but could provide greater insights into the development of novel and personalized countermeasures for maintaining or improving orthostatic tolerance during heat stress. This development will be especially impactful in occuational settings and clinical situations that present with orthostatic intolerance and/or central hypovolemia. Such investigations should be considered of vital importance given the impending increased incidence of heat events, and associated cardiovascular challenges that are predicted to occur with the ensuing changes in climate.

Elevated Core and Skin Temperatures Independently Attenuate Simulated Hemorrhagic Tolerance

Warming a hemorrhaging victim is the standard of care. However, heating can be detrimental to the maintenance of arterial pressure and cerebral perfusion. Purpose: To test the hypothesis that moder...

What is the central question of this study? Does baroreceptor unloading during passive hyperthermia contribute to increases in ventilation and decreases in end-tidal carbon dioxide during that exposure? What is the main finding and its importance? Hyperthermic hyperventilation is not mitigated by expanding central blood volume and reloading the cardiopulmonary baroreceptors via rapid saline infusion or by reloading the arterial baroreceptors via phenylephrine administration. The absence of a reduction in ventilation upon reloading the baroreceptors to pre-hyperthermic levels indicates that cardiopulmonary and arterial baroreceptor unloading with hyperthermia is unlikely to contribute to hyperthermic hyperventilation in humans. This study tested the hypothesis that baroreceptor unloading during passive hyperthermia contributes to increases in ventilation and decreases in end-tidal partial pressure of carbon dioxide (P ET ,CO2) during that exposure. Two protocols were performed, in which healthy subjects underwent passive hyperthermia (increasing intestinal temperature by ∼1.8°C) to cause a sustained increase in ventilation and reduction in P ET ,CO2. Upon attaining hyperthermic hyperventilation, in protocol 1 (n = 10; three females) a bolus (19 ± 2 ml kg(-1) ) of warm (∼38°C) isotonic saline was rapidly (5-10 min) infused intravenously to restore reductions in central venous pressure, whereas in protocol 2 (n = 11; five females) phenylephrine was infused intravenously (60-120 μg min(-1) ) to return mean arterial pressure to normothermic levels. In protocol 1, hyperthermia increased ventilation (by 2.2 ± 1.7 l min(-1) , P 0.01), while reducing P ET ,CO2 (by 4 ± 3 mmHg, P = 0.04) and central venous pressure (by 5 ± 1 mmHg, P0.01). Saline infusion increased central venous pressure by 5 ± 1 mmHg (P 0.01), restoring it to normothermic values, but did not change ventilation or P ET ,CO2 (P 0.05). In protocol 2, hyperthermia increased ventilation (by 5.0 ± 2.7 l min(-1) , P0.01) and reduced P ET ,CO2 (by 5 ± 2 mmHg, P 0.01) and mean arterial pressure (by 9 ± 7 mmHg, P0.01). Phenylephrine infusion increased mean arterial pressure by 12 ± 3 mmHg (P 0.01), restoring it to normothermic values, but did not change ventilation or P ET ,CO2 (P 0.05). The absence of a reduction in ventilation upon reloading the cardiopulmonary and arterial baroreceptors to pre-hyperthermic levels indicates that baroreceptor unloading with hyperthermia is unlikely to contribute to hyperthermic hyperventilation in humans.

We tested the hypothesis that attention, memory, and executive function are impaired to a greater extent in passively heat-stressed older adults than in passively heat-stressed younger adults. In a randomized, crossover design, 15 older (age: 69 ± 5 yr) and 14 younger (age: 30 ± 4 yr) healthy subjects underwent passive heat stress and time control trials. Cognitive tests (outcomes: accuracy and reaction time) from the CANTAB battery evaluated attention [rapid visual processing (RVP), choice reaction time (CRT)], memory [spatial span (SSP), pattern recognition memory (PRM)], and executive function [one touch stockings of Cambridge (OTS)]. Testing was undertaken on two occasions during each trial, at baseline and after internal temperature had increased by 1.0 ± 0.2°C or after a time control period. For tests that measured attention, reaction time during RVP and CRT was slower ( P ≤ 0.01) in the older group. During heat stress, RVP reaction time improved ( P < 0.01) in both groups. Heat stress had no effect ( P ≥ 0.09) on RVP or CRT accuracy in either group. For tests that measured memory, accuracy on SSP and PRM was lower ( P < 0.01) in the older group, but there was no effect of heat stress ( P ≥ 0.14). For tests that measured executive function, overall, accuracy on OTS was lower, and reaction time was slower in the older group ( P ≤ 0.05). Reaction time generally improved during heat stress, but there was no effect of heat stress on accuracy in either group. These data indicate that moderate increases in body temperature during passive heat stress do not differentially compromise cognitive function in younger and older adults.

The influence of thermoreceptors in human facial skin on thermoeffector responses is equivocal; furthermore, the presence of thermoreceptors in the respiratory tract and their involvement in thermal homeostasis has not been elucidated. This study tested the hypothesis that hot air directed on the face and inhaled during whole body passive heat stress elicits an earlier onset and greater sensitivity of cutaneous vasodilation and sweating than that directed on an equal skin surface area away from the face. Six men and two women completed two trials separated by ∼1 wk. Participants were passively heated (water-perfused suit; core temperature increase ∼0.9°C) while hot air was directed on either the face or on the lower leg (counterbalanced). Skin blood flux (laser-Doppler flowmetry) and local sweat rate (capacitance hygrometry) were measured at the chest and one forearm. During hot-air heating, local temperatures of the cheek and leg were 38.4 ± 0.8°C and 38.8 ± 0.6°C, respectively ( P = 0.18). Breathing hot air combined with facial heating did not affect mean body temperature onsets ( P = 0.97 and 0.27 for arm and chest sites, respectively) or slopes of cutaneous vasodilation ( P = 0.49 and 0.43 for arm and chest sites, respectively), or the onsets ( P = 0.89 and 0.94 for arm and chest sites, respectively), or slopes of sweating ( P = 0.48 and 0.65 for arm and chest sites, respectively). Based on these findings, respiratory tract thermoreceptors, if present in humans, and selective facial skin heating do not modulate thermoeffector responses during passive heat stress.

Prior studies investigating carotid baroreflex control of the cutaneous vasculature have yielded mixed findings. However, previously used methodological and analytical techniques may limit the ability to detect carotid baroreflex-mediated changes in cutaneous vascular conductance (CVC). The aim of this study was to test the hypothesis that dynamic carotid baroreceptor stimulation (i.e. 5 s trials) using neck pressure (NP, simulated carotid hypotension) and neck suction (NS, simulated carotid hypertension) will decrease and increase CVC, respectively, during normothermic and whole-body heating conditions in resting humans. Data were obtained from nine subjects (age, 31 +/- 2 year). The ratio of forearm skin blood flux (laser-Doppler flowmetry) and arterial blood pressure (Finapres) was used as an index of CVC. Multiple 5 s trials of NP (+40(Torr)) and NS (-60(Torr)), as well as breath-hold/airflow control trials, were applied during end-expiratory breath-holds while subjects were normotheric and heat stressed (change in core temperature approximately 0.75 degrees C). CVC responses to each NP and NS trial were averaged into 1 s intervals during the following periods: 3 s prestimulus, 5 s during stimulus, and 5 s poststimulus. Peak CVC responses (3 s average) to NP and NS were compared to prestimulus values using paired t test. During normothermia, NP decreased CVC by 0.032 +/- 0.007 arbitrary units (a.u.) mmHg(-1); (P < 0.05); however, breath-hold/airflow control trials resulted in similar decreases in CVC. NS did not change CVC (Delta = 0.002 +/- 0.005 a.u. mmHg(-1); P = 0.63). During whole-body heating, NP decreased CVC (by 0.16 +/- 0.04 a.u. mmHg(-1); (P < 0.05), whereas NS increased CVC by 0.07 +/- 0.03 a.u. mmHg(-1); (P < 0.05). Furthermore, these changes were greater than, or directionally different from, the breath-hold/airflow control trials. These findings indicate that carotid baroreceptor stimulation elicits dynamic changes in CVC and that these changes are more apparent during whole-body heating.

Given the large increase in cutaneous vascular conductance (CVC) during whole-body heat stress, this vascular bed is important in the regulation of blood pressure during orthostatic stress. In this thermal state, changes in CVC are reported to be due to withdrawal of active vasodilator activity. The purpose of this study was to identify, contrary to the current line of thinking, whether cutaneous vasoconstrictor neural activity is enhanced and capable of contributing to reductions in CVC during an orthostatic challenge of heat-stressed individuals. Healthy normotensive subjects were pretreated, subcutaneously, with botulinum toxin A (BTX-A) to inhibit the release of neurotransmitters from cutaneous active vasodilator nerves. On the experimental day, microdialysis probes were placed in the BTX-A-treated site and in an adjacent untreated site. In protocol 1, internal temperature was elevated ∼0.7°C, followed by the application of lower body negative pressure (LBNP; −30 mmHg). LBNP reduced CVC at the BTX-A-treated sites (Δ4.2 ± 2.9%max), as well as at the control site (Δ9.8 ± 4.1%max). In protocol 2, after confirming the absence of cutaneous vasodilatation at the BTX-A-treated site during whole-body heating, CVC at this site was elevated to a similar level relative to the control site (55.4 ± 13.4 versus 60.7 ± 10.4%max, respectively) via intradermal administration of isoproterenol prior to LBNP. Similarly, when flow was matched between sites, LBNP reduced CVC at both the BTX-A-treated (Δ15.3 ± 4.6%max) and the control sites (Δ8.8 ± 5.6%max). These data suggest that the cutaneous vasoconstrictor system is engaged and is capable of decreasing CVC during an orthostatic challenge in heat-stressed individuals.

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; r2= 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; r2= 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; r2= 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; r2= 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.

Skin sympathetic nerve activity (SSNA) exhibits low- and high-frequency spectral components in normothermic subjects. However, spectral characteristics of SSNA in heat-stressed subjects are unknown. Because the main components of the integrated SSNA during heat stress (sudomotor/vasodilator activities) are different from those during normothermia and cooling (vasoconstrictor activity), we hypothesize that spectral characteristics of SSNA in heat-stressed subjects will be different from those in subjects subjected to normothermia or cooling. In 17 healthy subjects, SSNA, electrocardiogram, arterial blood pressure (via Finapres), respiratory activity, and skin blood flow were recorded during normothermia and heat stress. In 7 of the 17 subjects, these variables were also recorded during cooling. Spectral characteristics of integrated SSNA, R-R interval, beat-by-beat mean blood pressure, skin blood flow variability, and respiratory excursions were assessed. Heat stress and cooling significantly increased total SSNA. SSNA spectral power in the low-frequency (0.03–0.15 Hz), high-frequency (0.15–0.45 Hz), and very-high-frequency (0.45–2.5 Hz) regions was significantly elevated by heat stress and cooling. Interestingly, heat stress caused a greater relative increase of SSNA spectral power within the 0.45- to 2.5-Hz region than in the other spectral ranges; cooling did not show this effect. Differences in the SSNA spectral distribution between normothermia/cooling and heat stress may reflect different characteristics of central modulation of vasoconstrictor and sudomotor/vasodilator activities.

Cutaneous vascular conductance (CVC) decreases during isometric handgrip exercise in heat stressed individuals, and we hypothesized that central command is involved in this response. Seven subjects performed 2 min of isometric handgrip exercise (35% of maximal voluntary contraction) followed by postexercise ischaemia in normothermia and during heat stress (increase in internal temperature approximately 1 degrees C). To augment the contribution of central command independent of force generation, on a separate day the protocol was repeated following partial neuromuscular blockade (PNB; i.v. cisatracurium). Forearm skin blood flow was measured by laser-Doppler flowmetry, and CVC was the ratio of skin blood flow to mean arterial pressure. The PNB attenuated force production despite encouragement to attain the same workload. During the heat stress trials, isometric exercise decreased CVC by approximately 12% for both conditions, but did not change CVC in either of the normothermic trials. During isometric exercise in the heat, the increase in mean arterial pressure (MAP) was greater during the control trial relative to the PNB trial (31.0+/-9.8 versus 18.6+/-6.4 mmHg, P

This investigation tested the hypothesis that cholinergic sweat function of individuals with multiple sclerosis (MS) (MS-Con; n = 10) is diminished relative to matched healthy control subjects (Con; n = 10). In addition, cholinergic sweat function was determined before and after 15 wk of aerobic training in a subgroup of individuals with MS (MS-Ex; n = 7). Cholinergic sweating responses were assessed via pilocarpine iontophoresis on ventral forearm skin. A collection disk placed over the stimulated area collected sweat for 15 min. Sweat rate (SR) was calculated by dividing sweat collector volume by collection area and time. Iodine-treated paper was applied to the stimulated area to measure number of activated sweat glands (ASG). Sweat gland output (SGO) was calculated by dividing SR by density of glands under the collector. Sweat gland function was determined in MS-Ex to test the hypothesis that exercise training would increase sweating responses. No differences in ASG were observed between MS-Con and Con. SR and SGO in MS-Con [0.18 mg·cm−2·min−1(SD 0.08); 1.74 μg·gland−1·min−1(SD 0.79), respectively] were significantly lower ( P ≤ 0.05) than in Con [0.27 mg·cm−2·min−1(SD 0.10); 2.43 μg·gland−1·min−1(SD 0.69)]. Aerobic exercise training significantly ( P ≤ 0.05) increased peak aerobic capacity in MS-Ex [1.86 (SD 0.75) vs. 2.10 (SD 0.67) l/min] with no changes in ASG, SR, and SGO. Sweat gland function in individuals with MS is impaired relative to healthy controls. Fifteen weeks of aerobic training did not increase stimulated sweating responses in individuals with MS. Diminished peripheral sweating responses may be a consequence of impairments in autonomic control of sudomotor function.

Conflicting reports exist about the role of baroreflexes in efferent control of eccrine sweat rate. These conflicting reports may be due to differing mean body temperatures between studies. The purpose of this project was to test the hypothesis that mean body temperature modulates the effect of head-up tilt on sweat rate and skin sympathetic nerve activity (SSNA). To address this question, mean body temperature (0.9·internal temperature + 0.1·mean skin temperature), SSNA (microneurography of peroneal nerve, n = 8), and sweat rate (from an area innervated by the peroneal nerve and from two forearm sites, one perfused with neostigmine to augment sweating at lower mean body temperatures and the second with the vehicle, n = 12) were measured in 13 subjects during multiple 30° head-up tilts during whole body heating. At the end of the heat stress, mean body temperature (36.8 ± 0.1 to 38.0 ± 0.1°C) and sweat rate at all sites were significantly elevated. No significant correlations were observed between mean body temperature and the change in SSNA during head-up tilt ( r = 0.07; P = 0.62), sweating within the innervated area ( r = 0.06; P = 0.56), sweating at the neostigmine treated site ( r = 0.04; P = 0.69), or sweating at the control site ( r = 0.01; P = 0.94). Also, for each tilt throughout the heat stress, there were no significant differences in sweat rate (final tilt sweat rates were 0.69 ± 0.11 and 0.68 ± 0.11 mg·cm−2·min−1 within the innervated area; 1.04 ± 0.16 and 1.06 ± 0.16 mg·cm−2·min−1 at the neostigmine-treated site; and 0.85 ± 0.15 and 0.85 ± 0.15 mg·cm−2·min−1 at the control site, for supine and tilt, respectively). Hence, these data indicate that mean body temperature does not modulate eccrine sweat rate during baroreceptor unloading induced via 30° head-up tilt.

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 × 10−6–8.4 × 10−3m) 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 × 10−4m (control: 63.0 ± 4.1%, SNP 8.4 × 10−6m: 57.1 ± 4.7%, SNP 8.4 × 10−5m: 57.0 ± 3.6%, SNP 8.4 × 10−4m: 44.5 ± 5.4% and SNP 8.4 × 10−3m: 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.

Thoracic surgical sympathectomy is often performed to treat primary palmar and axillary hyperhidrosis. An increase in palmar skin temperature is frequently used to identify the success of the procedure. Because changes in palmar skin temperature occur secondary to changes in skin blood flow, the objective of this study was to test the hypothesis that monitoring palmar skin blood flow would provide greater temporal resolution relative to monitoring palmar skin temperature. In 11 patients with palmar and/or axillary hyperhidrosis, we measured palmar skin temperature and blood flow (via laser Doppler flowmetry) throughout the sympathectomy procedure. Five minutes after the initial cautery, skin blood flow increased from 48 +/- 7 perfusion units to 121 +/- 17 perfusion units (P0.001), whereas no significant change in temperature was observed (31.0 degrees C +/- 0.5 degrees C to 31.3 degrees C +/- 0.5 degrees C; P0.05). The time required to reach peak skin blood flow (22 +/- 3 min) was significantly less than the time required to reach peak skin temperature (34 +/- 0.3 min; P0.001). Finally at 5, 10, and 15 min after the initial cautery, skin blood flow increased to a larger percentage of the total increase in skin blood flow relative skin temperature (all P0.006). These data suggest that monitoring skin blood flow provides greater temporal resolution when compared with monitoring skin temperature during thoracic sympathectomy. However, the initial cautery of the parietal pleura over the ganglion may result in increases in skin blood flow before physical disruption of the ganglion. This occurrence may limit the utility of skin blood-flow measurements in identifying the success of the procedure.

The human cerebral vasculature is highly sensitive to changes in arterial blood gases (i.e. arterial carbon dioxide () and oxygen () tensions), such that hypercapnia/hypoxia and hypocapnia/hyperoxia cause global increases and decreases in cerebral blood flow. It is generally accepted that all cerebral arter-ioles – traditionally considered to be the regulators of brain blood flow – are equally sensitive to changes in arterial blood gases. However, this classic dogma may not be the case.

The objective of this study was to identify whether muscle mechanoreceptor stimulation is capable of modulating sweat rate. Seven healthy subjects performed two 20-min bouts of supine exercise on a tandem cycle ergometer (60 rpm at 65% of maximal heart rate). After one bout, the subject stopped exercising (i.e., no pedaling), whereas, after the other bout, the subject's legs were passively cycled (at 60 rpm) via a second person cycling the tandem ergometer. This allows for mechanical stimulation of muscle with minimal activation of central command. Esophageal temperature (Tes), mean skin temperature (T̄sk), heart rate, mean arterial blood pressure, oxygen consumption, cutaneous vascular conductance (CVC), and sweat rate were not different during the two exercise bouts. Regardless of the mode of exercise recovery, there were no differences in Tes, T̄sk, or CVC. In contrast, early in the recovery period, chest and forearm sweat rate were significantly greater in the passive cycling recovery mode relative to the no-pedaling condition (chest: 0.57 ± 0.13 vs. 0.39 ± 0.14, forearm: 0.30 ± 0.05 vs. 0.12 ± 0.02 mg·cm-2·min-1; both P < 0.05). These results suggested that muscle mechanoreceptor stimulation to the previously activated muscle is capable of modulating sweat rate.

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.

Background and Purpose— The aim of this study was to differentiate the mechanical effects of the Valsalva maneuver (VM) from the effects of changes in autonomic neural activity on cerebral hemodynamics in humans. Methods— Nine healthy subjects performed the VM before and after autonomic ganglionic blockade with trimethaphan. Blood pressure (BP) was measured in the radial artery with an indwelling catheter or at the finger by Finapres. Cerebral blood flow (CBF) velocity was measured in the middle cerebral artery with transcranial Doppler; end-tidal CO 2 was measured by mass spectrometry. Results— Before blockade, during phase II of the VM, BP was reduced by 27% and CBF velocity was reduced by 33% (magnitude of changes during phase II divided by baseline measurements before the VM, P Conclusions— After ganglionic blockade, cerebral autoregulation is unable to prevent the substantial fall in CBF induced by the marked reduction in BP during the VM. Enhanced phase IV increases in both CBF velocity and CVCI reflect the intrinsic characteristics of cerebral hyperemic responses, which are likely modified in part by the removal of vasoconstrictor effects of autonomic neural activity elicited during the VM.

Whole body heating increases muscle sympathetic nerve activity (MSNA); however, the effect of heat stress on spectral characteristics of MSNA is unknown. Such information may provide insight into mechanisms of heat stress-induced MSNA activation. The purpose of the present study was to test the hypothesis that heat stress-induced changes in systolic blood pressure variability parallel changes in MSNA variability. In 13 healthy subjects, MSNA, electrocardiogram, arterial blood pressure (via Finapres), and respiratory activity were recorded under both normothermic and heat stress conditions. Spectral characteristics of integrated MSNA, R-R interval, systolic blood pressure, and respiratory excursions were assessed in the low (LF; 0.03–0.15 Hz) and high (HF; 0.15–0.45 Hz) frequency components. Whole body heating significantly increased skin and core body temperature, MSNA burst rate, and heart rate, but not mean arterial blood pressure. Systolic blood pressure and R-R interval variability were significantly reduced in both the LF and HF ranges. Compared with normothermic conditions, heat stress significantly increased the HF component of MSNA, while the LF component of MSNA was not altered. Thus the LF-to-HF ratio of MSNA oscillatory components was significantly reduced. These data indicate that the spectral characteristics of MSNA are altered by whole body heating; however, heat stress-induced changes in MSNA do not parallel changes in systolic blood pressure variability. Moreover, the reduction in LF component of systolic blood pressure during heat stress is unlikely related to spectral changes in MSNA.

The purpose of this study was to identify whether baroreceptor unloading was responsible for less efficient heat loss responses (i.e., skin blood flow and sweat rate) previously reported during inactive compared with active recovery after upright cycle exercise (Carter R III, Wilson TE, Watenpaugh DE, Smith ML, and Crandall CG. J Appl Physiol 93: 1918-1929, 2002). Eight healthy adults performed two 15-min bouts of supine cycle exercise followed by inactive or active (no-load pedaling) supine recovery. Core temperature (Tcore), mean skin temperature (Tsk), heart rate, mean arterial blood pressure (MAP), thoracic impedance, central venous pressure ( n = 4), cutaneous vascular conductance (CVC; laser-Doppler flux/MAP expressed as percentage of maximal vasodilation), and sweat rate were measured throughout exercise and during 5 min of recovery. Exercise bouts were similar in power output, heart rate, Tcore, and Tsk. Baroreceptor loading and thermal status were similar during trials because MAP (90 ± 4, 88 ± 4 mmHg), thoracic impedance (29 ± 1, 28 ± 2 Ω), central venous pressure (5 ± 1, 4 ± 1 mmHg), Tcore(37.5 ± 0.1, 37.5 ± 0.1°C), and Tsk(34.1 ± 0.3, 34.2 ± 0.2°C) were not significantly different at 3 min of recovery between active and inactive recoveries, respectively; all P > 0.05. At 3 min of recovery, chest CVC was not significantly different between active (25 ± 6% of maximum) and inactive (28 ± 6% of maximum; P > 0.05) recovery. In contrast, at this time point, chest sweat rate was higher during active (0.45 ± 0.16 mg·cm-2·min-1) compared with inactive (0.34 ± 0.19 mg·cm-2·min-1; P < 0.05) recovery. After exercise CVC and sweat rate are differentially controlled, with CVC being primarily influenced by baroreceptor loading status while sweat rate is influenced by other factors.

Spaceflight and its bed rest analog [6° head-down tilt (HDT)] decrease plasma and blood volume and aerobic capacity. These responses may be associated with impaired thermoregulatory responses observed during exercise and passive heating after HDT exposure. This project tested the hypothesis that dynamic exercise during 13 days of HDT bed rest preserves thermoregulatory responses. Throughout HDT bed rest, 10 subjects exercised for 90 min/day (75% of pre-HDT maximum heart rate; supine). Before and after HDT bed rest, each subject exercised in the supine position at the same workload in a 28°C room. The internal temperature (Tcore) threshold for the onset of sweating and cutaneous vasodilation, as well as the slope of the relationship between the elevation in Tcore relative to the elevation in sweat rate (SR) and cutaneous vascular conductance (CVC; normalized to local heating maximum), were quantified pre- and post-HDT. Tcore thresholds for the onset of cutaneous vasodilation on the chest and forearm (chest: 36.79 ± 0.12 to 36.94 ± 0.13°C, P = 0.28; forearm: 36.76 ± 0.12 to 36.91 ± 0.11°C, P = 0.16) and slope of the elevation in CVC relative to Tcore (chest: 77.9 ± 14.2 to 80.6 ± 17.2%max/°C; P = 0.75; forearm: 76.3 ± 11.8 to 67.5 ± 14.3%max/°C, P = 0.39) were preserved post-HDT. Moreover, the Tcore threshold for the onset of SR (36.66 ± 0.12 to 36.74 ± 0.10°C; P = 0.36) and the slope of the relationship between the elevation in SR and the elevation in Tcore (1.23 ± 0.19 to 1.01 ± 0.14 mg · cm-2 · min-1 · °C-1; P = 0.16) were also maintained. Finally, after HDT bed rest, peak oxygen uptake and plasma and blood volumes were not different relative to pre-HDT bed rest values. These data suggest that dynamic exercise during this short period of HDT bed rest preserves thermoregulatory responses.

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° 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°C for 45 min. Sweat gland function was assessed by administering 1 × 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.

Given differences in sympathetic innervation to glabrous and nonglabrous skin, we tested the hypothesis that muscle metaboreceptor regulation of cutaneous vascular conductance (CVC) differs between these skin regions. Subjects ( n = 21) performed isometric handgrip exercise (IHG; 50% maximal voluntary contraction for 60 s), followed by 2 min of postexercise ischemia. Throughout IHG and postexercise ischemia, CVC was measured from glabrous (palm) and nonglabrous (forearm and chest) regions contralateral to the exercising arm. These procedures were conducted after the subjects had been exposed to an ambient temperature of 35°C and a relative humidity of 50% for 60 min. These thermal conditions were intended to cause slight increases in cutaneous blood flow via sympathetic withdrawal. Esophageal, sublingual, and mean skin temperatures did not change markedly during IHG or postexercise ischemia. During IHG, forearm CVC did not change, chest CVC increased slightly, and palm CVC decreased substantially (from 100 to 34.8 ± 3.5%; P = 0.001). During muscle metaboreceptor stimulation due to postexercise ischemia, CVC from nonglabrous regions returned to preexercise baselines, whereas CVC at the palm remained below preexercise baseline (68.2 ± 4.2%; P = 0.001 relative to preexercise baseline). These results indicate that in mildly heated humans muscle metaboreflex stimulation is capable of modulating CVC in glabrous, but not in nonglabrous, skin.

INTRODUCTION: Heat stress significantly reduces orthostatic tolerance in humans. The mechanism(s) causing this response remain unknown. The purpose of this review article is to present data pertaining to the hypothesis that reduced orthostatic tolerance in heat stressed individuals is a result of heat stress induced alterations in baroflex function. METHODS: In both normothermic and heat stressed conditions baroreflex responsiveness was assessed via pharmacological and non-pharmacological methods. In addition, the effects of heat stress on post-synaptic vasoconstrictor responsiveness were assessed. RESULTS: Generally, whole body heating did not alter baroreflex sensitivity defined as the gain of the linear portion of the baroreflex curve around the operating point. However, whole body heating shifted the baroreflex curve to the prevailing (i.e. elevated) heart rate and muscle sympathetic nerve activity. Finally, the heat stress impaired vasoconstrictor responses to exogenous administration of adrenergic agonists. CONCLUSION: Current data do not support the hypothesis that reduced orthostatic tolerance associated with heat stress in humans is due to impaired baroreflex responsiveness. This phenomenon may be partially due to the effects of heat stress on reducing vasoconstrictor responsiveness.

Nitric oxide (NO) contributes to active cutaneous vasodilation during a heat stress in humans. Given that acetylcholine is released from cholinergic nerves during whole body heating, coupled with evidence that acetylcholine causes vasodilation via NO mechanisms, it is possible that release of acetylcholine in the dermal space contributes to cutaneous vasodilation during a heat stress. To test this hypothesis, in seven subjects skin blood flow (SkBF) and sweat rate were simultaneously monitored over three microdialysis membranes placed in the dermal space of dorsal forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine (10 μM), the second membrane was perfused with the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 10 mM) dissolved in the aforementioned neostigmine solution (l-NAMENeo), and the third membrane was perfused with Ringer solution as a control site. Each subject was exposed to ∼20 min of whole body heating via a water-perfused suit, which increased mean body temperature from 36.4 ± 0.1 to 37.5 ± 0.1°C ( P < 0.05). After the heat stress, SkBF at each site was normalized to its maximum value, identified by administration of 28 mM sodium nitroprusside. Mean body temperature threshold for cutaneous vasodilation was significantly lower at the neostigmine-treated site relative to the other sites (neostigmine: 36.6 ± 0.1°C, l-NAMENeo: 37.1 ± 0.1°C, control: 36.9 ± 0.1°C), whereas no significant threshold difference was observed between thel-NAMENeo-treated and control sites. At the end of the heat stress, SkBF was not different between the neostigmine-treated and control sites, whereas SkBF at thel-NAMENeo-treated site was significantly lower than the other sites. These results suggest that acetylcholine released from cholinergic nerves is capable of modulating cutaneous vasodilation via NO synthase mechanisms early in the heat stress but not after substantial cutaneous vasodilation.

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).

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° 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-tiltcool), and heat stress plus skin-surface cooling 1 min before and throughout tilting (HT-tiltcool). Heating and cooling were accomplished by perfusing 46 and 15°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-tiltcool, or HT-tiltcool. During the HT-tilt procedure, mean arterial blood pressure (MAP) and cerebral blood flow velocity (CBFV) decreased. However, during HT-tiltcool, 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.

To identify whether whole body heating alters arterial baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA and beat-by-beat arterial blood pressure were recorded in seven healthy subjects during acute hypotensive and hypertensive stimuli in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature ( P < 0.01), MSNA ( P < 0.01), heart rate ( P< 0.01), and skin blood flow ( P < 0.001), whereas mean arterial blood pressure did not change significantly ( P > 0.05). During both normothermic and heat stress conditions, MSNA increased and then decreased significantly when blood pressure was lowered and then raised via intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure during heat stress (−128.3 ± 13.9 U · beats−1 · mmHg−1) was similar ( P = 0.31) with normothermia (−140.6 ± 21.1 U · beats−1 · mmHg−1). Moreover, no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that arterial baroreflex modulation of MSNA and heart rate are not altered by whole body heating, with the exception of an upward shift of these baroreflex curves to accommodate changes in these variables that occur with whole body heating.

What is the central question of this study? The effect of ageing on hyperthermia-induced changes in cardiac function is unknown. What is the main finding and its importance? Using echocardiography, we show that during hyperthermia the systolic and diastolic function can be appropriately augmented to meet cardiac demand in healthy older adults, although overall age-related impairments remain. One exception was late diastolic ventricular filling [i.e. E/A ratio and A/(A + E) ratio], which in the older adults was not further augmented during hyperthermia, unlike their young counterparts. To meet cardiac demand, therefore, healthy older adults appear to depend on an increased left ventricular systolic strain and proportion of their cardiac reserve. The effect of ageing on hyperthermia-induced changes in cardiac function is unknown. This study tested the hypothesis that hyperthermia-induced changes in left ventricular systolic and diastolic function are attenuated in older adults when compared with young adults. Eight older (71 ± 5 years old) and eight young adults (29 ± 5 years old), matched for sex, physical activity and body mass index, underwent whole-body passive hyperthermia. Mean arterial pressure (Finometer Pro), heart rate, forearm vascular conductance (venous occlusion plethysmography) and echocardiographic indices of diastolic and systolic function were measured during a normothermic supine period and again after an increase in internal temperature of ∼1.0 °C. Hyperthermia decreased mean arterial pressure and left ventricular end-diastolic volumes and increased heart rate to a similar extent in both groups (P0.05). Ageing did not alter the magnitude of hyperthermia-induced changes in indices of systolic (lateral mitral annular S' velocity) or diastolic function (lateral mitral annular E' velocity, peak early diastolic filling and isovolumic relaxation time; P0.05). However, with hyperthermia the global longitudinal systolic strain increased in the older group, but was unchanged in the young group (P = 0.03). Also, older adults were unable to augment late diastolic ventricular filling [i.e. E/A ratio and A/(A + E) ratio] during hyperthermia, unlike the young (P0.05). These findings indicate that older adults depend on a greater systolic contribution (global longitudinal systolic strain) to meet hyperthermic demand and that the atrial contribution to diastolic filling was not further augmented in older adults when compared with young adults.