Whole-body Heat Stress Research Articles

Does acute heat stress alter lactation performance in postpartum mothers?

Introduction: Heat stress has been shown to acutely decrease lactation performance in various mammalian species, however whether a similar effect is present in humans remains largely unexplored. Objective and hypothesis: The objective of the present study was to determine whether an acute whole-body heat stress reduces lactation performance in postpartum mothers in the proceeding 24 h. Methods: To date, 9 postpartum mothers (32±4 y; 1.6 ±0.1 m; 67±13 kg; 8±3 months postpartum) have participated in the study. During the 24 h period before and after the acute passive heat stress, participants were asked to record their voluntary fluid intake and their milk production defined as the volume of expressed milk and/or breastfeeding volume based on the baby’s weight before and immediately after nursing, accounting for evaporative water losses. The passive heat stress protocol involved participants laying supine while donning a tube-lined garment continuously perfused with 49°C water for 60 minutes. Rectal temperature and heart rate were measured during the passive heat stress intervention to confirm thermal strain, and whole-body sweat losses were calculated as the net difference in body mass following passive heat stress. Results: The 60-minute passive heat stress protocol increased rectal temperature by 0.4±0.3°C, increased heart rate (17±12 BPM), and resulted in a whole-body sweat loss of 278±201 g. The frequency of lactation was similar during the 24 h before (5.4±1.6 times) and 24 h after (5.1±1.1 times, P=0.20) acute passive heat stress. The total volume of human milk production in the 24 h prior to heat stress was not different to the 24 h following heat stress (pre: 327±123 ml, post: 312±148 ml, P=0.33). Maternal fluid intake was higher during the 24 h after passive heat stress (1561±73 ml) in comparison to the 24 h before (1377±244 ml, P=0.05). Conclusion: Preliminary data suggests that an acute bout of whole-body heat stress does not modulate lactation performance in postpartum mothers. This research was supported by Dr. Ravanelli’s Natural Sciences and Engineering Research Council of Canada Discovery Grant (PIN#2022-05096). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Obesity increases cardiovascular strain during passive heat stress in middle-aged women

Heat waves are becoming more frequent and severe, and cardiovascular events are a contributing cause in most heat-related deaths. Obesity is reported in over 40% of adults over the age of 40 yrs, and is associated with greater heat-related mortality, although the precise mechanisms are not well-understood. To determine whether obesity increases heat-related cardiovascular vulnerability in middle-aged women, this study examined cardiovascular responses to passive whole-body heat stress in four obese (54 ± 11 yr; BMI: 33.1 ± 2.8) and four non-obese (55 ± 5 yr; BMI: 23.6 ± 0.8) middle-aged women. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF) while reflex vasodilation was induced via whole-body heating using a water-perfused suit. After a 1.0°C rise in gastrointestinal temperature (ΔTgi), local skin temperature was increased to 43°C to elicit a maximal vasodilation response. Cutaneous vascular conductance was calculated (CVC = LDF/mean arterial pressure) and expressed as a percentage of maximum (%CVCmax) for each ΔTgi of 0.1°C. Heart rate (HR) was measured continuously and blood pressure (BP) was measured at each ΔTgi of 0.1°C, and rate pressure product (RPP; HR x systolic BP) was calculated as an index of cardiac strain. Percent body fat was measured with dual x-ray absorptiometry (DXA). Time to reach a ΔTgi of 1.0°C was not different between groups (Obese: 65 ± 16 min; Non-obese: 63 ± 13 min; p = 0.85). There was no group difference in CVCmax (Obese: 2.5 ± 0.6; Non-obese: 2.01 ± 0.3; p = 0.19). Likewise, there were no group differences in %CVCmax at baseline or any point throughout local heating (all p ≥ 0.47). RPP was not different between groups at baseline (Obese: 8840 ± 1160; Non-obese: 7492 ± 1081; p > 0.99), but increased to a greater degree in obese women such that there was a significant difference at ΔTgi of 1.0°C (Obese: 14162 ± 1910; Non-obese: 11393 ± 3448; p = 0.05). Further, %BF was directly related to peak RPP (p = 0.03; r = 0.75), but not resting RPP (p = 0.16). Obese women demonstrated an exaggerated RPP response for a given rise in %CVC (p < 0.0001, r = 0.82) relative to non-obese women (p = 0.21, r = 0.19; difference between slopes = 0.002). These data suggest that although thermoregulatory responses are preserved in obese middle-aged women relative to their non-obese counterparts, cardiovascular strain may be exaggerated in obese women for a given magnitude of thermoregulatory response, potentially contributing to increased heat-related mortality. This work was supported by NIH F32 AG079581 (STW) and a seed grant from the University of Georgia Obesity Research Initiative (STW). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of heat stress on heat shock protein expression and hypertrophy-related signaling in the skeletal muscle of trained individuals.

Muscle mass is balanced between hypertrophy and atrophy by cellular processes, including activation of the protein kinase B-mechanistic target of rapamycin (Akt-mTOR) signaling cascade. Stressors apart from exercise and nutrition, such as heat stress, can stimulate the heat shock protein A (HSPA) and C (HSPC) families alongside hypertrophic signaling factors and muscle growth. The effects of heat stress on HSP expression and Akt-mTOR activation in human skeletal muscle and their magnitude of activation compared with known hypertrophic stimuli are unclear. Here, we show a single session of whole body heat stress following resistance exercise increases the expression of HSPA and activation of the Akt-mTOR cascade in skeletal muscle compared with resistance exercise in a healthy, resistance-trained population. Heat stress alone may also exert similar effects, though the responses are notably variable and require further investigation. In addition, acute heat stress in C2C12 muscle cells enhanced myotube growth and myogenic fusion, albeit to a lesser degree than growth factor-mediated hypertrophy. Though the mechanisms by which heat stress stimulates hypertrophy-related signaling and the potential mechanistic role of HSPs remain unclear, these findings provide additional evidence implicating heat stress as a novel growth stimulus when combined with resistance exercise in human skeletal muscle and alone in isolated murine muscle cells. We believe these findings will help drive further applied and mechanistic investigation into how heat stress influences muscular hypertrophy and atrophy.NEW & NOTEWORTHY We show that acute resistance exercise followed by whole body heat stress increases the expression of HSPA and increases activation of the Akt-mTOR cascade in a physically active and resistance-trained population.

Neuromuscular and gene signaling responses to passive whole-body heat stress in young adults

This study aimed to investigate whether acute passive heat stress 1) decreases muscle Maximal Voluntary Contraction (MVC); 2) increases peripheral muscle fatigue; 3) increases spinal cord excitability, and 4) increases key skeletal muscle gene signaling pathways in skeletal muscle. Examining the biological and physiological markers underlying passive heat stress will assist us in understanding the potential therapeutic benefits. MVCs, muscle fatigue, spinal cord excitability, and gene signaling were examined after control or whole body heat stress in an environmental chamber (heat; 82 °C, 10% humidity for 30 min). Heart Rate (HR), an indicator of stress response, was correlated to muscle fatigue in the heat group (R = 0.59; p < 0.05) but was not correlated to MVC, twitch potentiation, and H reflex suppression. Sixty-one genes were differentially expressed after heat (41 genes >1.5-fold induced; 20 < 0.667 fold repressed). A strong correlation emerged between the session type (control or heat) and principal components (PC1) (R = 0.82; p < 0.005). Cell Signal Transduction, Metabolism, Gene Expression and Transcription, Immune System, DNA Repair, and Metabolism of Proteins were pathway domains with the largest number of genes regulated after acute whole body heat stress. Acute whole-body heat stress may offer a physiological stimulus for people with a limited capacity to exercise.

Comparing the Effects of 30‐ and 60‐min of Acute Whole‐Body Passive Heat Stress on Peripheral Vascular Function in Older Adults

IntroductionMacro‐ and microvascular dysfunction elevate the risk of cardiovascular disease (CVD). Heat therapy has the potential to improve vascular health and reduce CVD risk, but the optimal length of heat stress exposure is unknown. We hypothesized that 1) acute whole body heat stress (WBHS) would increase vascular function and 2) a longer WBHS period (30‐ vs 60‐min) would elicit a greater effect.Methods20 older adults (10 female; 64±7 y) underwent two separate periods of WBHS (30‐ vs 60‐min) via water perfused suit (48°C) in a randomized, counterbalanced design. Macrovascular function via flow‐mediated dilation (FMD) and microvascular function via skin reactive hyperemia (SKBF RH) were assessed before (PRE) and after (POST) WBHS. Core (Tcore; rectal) and skin (Tskin; 6‐site average) temperatures were monitored throughout. Repeated measures ANOVA were used to assess the effect of time (PRE vs POST) and visit (30‐ vs 60‐min) on all outcomes.ResultsTcore and Tskin increased after both WBHS periods (Tcore: 30‐min, PRE: 36.4±0.3, POST: 36.6±0.3°C; 60‐min, PRE: 36.4±0.3, POST: 36.8±0.2°C, p=0.001; Tskin: 30‐min, PRE: 33.5±0.6, POST: 36.3±0.4°C, p&lt;0.0005; 60‐min, PRE: 33.2±0.5°C, POST: 36.6±0.5°C, p&lt;0.0005). FMD% was unchanged (30‐min, PRE: 8.5±5.1%, POST: 7.1±4.2%; 60‐min, PRE: 7.7±3.9%, POST: 6.6±4.3%; p=0.10) after both WBHS periods. During RH, brachial artery shear rate area under the curve was higher after 30‐ (PRE: 17.08±9.57, POST: 26.34±13.06·10‐3 AUC; p=0.003) but not 60‐min (PRE: 21.06±12.30, POST: 27.83±19.32·10‐3 AUC; p=0.186). Total SKBFAUC increased following both 30‐ (PRE: 6.31±3.22, POST: 12.82±6.44·10‐3 AUC; p&lt;0.0005) and 60‐min (PRE: 6.01±3.24, POST: 9.609±4.882·10‐3 AUC; p=0.037), whereas peak SKBF fluxAUC increased following 30‐ (PRE: 1.86±1.54, POST: 4.15±3.07·10‐3 AUC; p=0.001) but not 60‐min (PRE: 1.58±1.31, POST: 2.93±2.77·10‐3 AUC; p=0.1113) of WBHS.DiscussionUp to 60‐min of acute WBHS does not change macrovascular function in older adults. Interestingly, WBHS might increase downstream microvascular functional capacity. The changes in microvascular function following 30‐min of WBHS may reflect early markers of the benefits of repeated whole body heat stress.

Calcium‐activated Chloride Channel TMEM16A/ANO1 Does Not Mediate the Regulation of Sweating and Cutaneous Vasodilation in Humans In Vivo

The regulation of human body temperature during a heat stress is dependent on the activation of the heat loss responses of cutaneous vasodilation and eccrine sweating. While significant advancements have been made in our understanding of the mechanisms governing their regulation, new potential modifiers such as transmembrane member 16A (TMEM16A), a Ca2+‐activated Cl‐ channel also known as anoctamin 1 (ANO1), continue to be identified. In vitro and animal studies suggest a role for TMEM16A in the regulation of sweat secretion and vascular tone. For example, Ca2+ induced Cl‐current was abolished in TMEM16A deficit, but not BEST2 deficit, NCL‐SG3 human eccrine sweat gland cell lines. Further, animal models showed the activation of TMEM16A on vascular smooth muscle cells blunts vasodilation. However, direct evidence supporting a role of TMEM16 in mediating cutaneous vasodilation as well as eccrine sweating in humans in vivo remains to be established. Therefore, we evaluated the hypothesis that TMEM16A mediates the regulation of sweating and cutaneous vasodilation during a whole‐body heat stress in young adults.Twelve young (24 ± 2 years) adults (6 females) underwent a whole‐body heat stress induced by a water‐perfused suit to raise core temperature 1.1±0.1ºC above baseline resting levels. Sweat rate (ventilated capsule) and cutaneous vascular conductance (assessed as skin blood flow/mean arterial pressure and normalised to maximal conductance achieved via simultaneous local skin heating to 44°C and administration of sodium nitroprusside) were assessed at four skin sites on the forearm treated with 1) lactated Ringers (control), 2) 5 % dimethyl sulfoxide serving as a vehicle control, 3) 1 mM T16Ainh‐A01 (a TMEM16A blocker) or 4) 2 mM benzbromarone (another TMEM16A blocker). All drugs were administered continuously via intradermal microdialysis.Sweat rate increased as heating continued at all skin sites (P &lt; 0.001 for a main effect of heating stage). Neither the main effect of treatment site nor the interaction between treatment site and heating stage was significant (both P ≥ 0.318). Cutaneous vascular conductance increased in parallel to elevations in core temperature (P &lt; 0.001 for a main effect of heating stage). Although no main effect of treatment site was observed (P = 0.109), a significant interaction between heating stage and treatment site was measured (P &lt; 0.001). Post‐hoc analysis revealed that cutaneous vascular conductance at the DMSO‐treated site was higher than the control site at baseline (P = 0.047). By contrast, cutaneous vascular conductance at moderate elevations in core temperature (i.e., ≥0.4‐0.8 °C) was greater at the control site relative to the DMSO‐treated site (all P ≤ 0.013). Importantly, no differences were measured in cutaneous vascular conductance between the DMSO‐treated site and TMEM16A blocker‐treated sites (all P ≥ 0.073).Taken together, our findings demonstrate for the first time that TMEM16A does not contribute to the regulation of sweating and cutaneous vasodilation during whole‐body heating in young adults in vivo.

Exercise Pressor Reflex is Attenuated during Moderate Whole‐Body Heating in Older Humans

Prior reports show that whole-body heat stress attenuates the pressor response to exercise in young healthy subjects. The effects of moderate whole-body heating (WBH, e.g. increase in internal temperature Tcore ~0.4-0.5 °C) on sympathetic and cardiovascular responses to exercise in older healthy humans remains unclear. We examined muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP) and heart rate (HR) in 14 older (62 ± 7 yrs. mean ± SD) healthy subjects during fatiguing isometric handgrip exercise and post exercise circulatory occlusion (PECO). The protocol was performed under normothermic and moderate WBH conditions during 2 visits. Under the moderate WBH condition (ΔTcore ~0.4 ± 0.1 °C), MAP decreased (90.0 ± 6.6 to 86.4 ± 7.1 mmHg), HR increased (60.8 ± 7.9 to 71.7 ± 9.7 beats/min), while MSNA was unchanged (34.7 ± 9.2 to 37.5 ± 15.4 bursts/min) from the baseline before heating. Hemodynamic variables and MSNA did not change significantly during the time control period in the normothermic trial. Compared with the normothermic trial, the absolute MAP during fatiguing exercise (102.7 ± 8.5 vs. 117.2 ± 11.4 mmHg) and PECO (98.2 ± 8.9 vs. 113.9 ± 12.5 mmHg) were lower during the WBH trial. Moreover, MSNA (Δ8.4 ± 6.5 vs. Δ14.0 ± 7.2 bursts/min) and MAP (Δ16.5 ± 7.5 vs. Δ23.2 ± 8.2 mmHg) responses (i.e. changes) to fatiguing exercise were also less than those seen during the normothermic trial. These data suggest that moderate WBH attenuates reflex exercise pressor responses in older healthy humans. Further studies are needed to examine if WBH can attenuate exercise pressor responses in patients with cardiovascular diseases.

Cholinergic nerve contribution to cutaneous active vasodilation in response to exercise heat‐loading is similar to passive whole‐body heat‐loading

Introduction Twenty-five years ago, Dean Kellogg and colleagues established the sympathetic cholinergic nerve co-transmitter theory for cutaneous active vasodilation (CAVD) during passive heating in humans. In this seminal study, pretreatment of the skin with botulinum toxin type-A (BOTOX), a presynaptic cholinergic nerve blocker, abolished CAVD during passive whole-body heat stress in six subjects. To date, these findings have not been confirmed. More recently, a clear role for NO in CAVD has been established, where NO accounts for up to 50% of CAVD. The specific isoform of NO-synthase has been reported to differ between CAVD in response to different thermal loading modalities (passive heating vs. exercise). These findings suggest that there may be mechanistic differences in the skin blood flow responses (SkBF) to hyperthermic challenge that are dependent on how thermal loading is accomplished. With this in mind, it is unknown if the cholinergic co-transmitter theory of CAVD applies to other thermal loading modalities such as exercise heat-loading. Therefore, this study sought to confirm the role of cholinergic nerve activation in CAVD during passive whole-body heat-loading and expand these findings to exercise heat-loading using a cross-over study design. It was hypothesized that CAVD during exercise and passive whole-body heating would both be abolished by BOTOX administration. Methods Eight young (18-30 years) recreationally-active individuals participated in both an exercise heat-loading study day (40% VO2peak, 1 hour; seated cycle ergometer) and a passive whole-body heat-loading study day (mean skin temperature clamp @ 39°C, ~1 hour; water-perfused suit, seated), in a randomized order. Cholinergic nerve blockade was achieved through BOTOX administration ~2 weeks prior to study days. Throughout heat-loading trials, SkBF was assessed at BOTOX treated and untreated sites using laser-doppler flowmetry. Results At rest, there were no differences in SkBF expressed as % CVCmax by site (BOTOX treated vs. untreated) or by modality (Exercise heat-loading vs. passive whole body heat-loading). The SkBF response, as a function of increasing internal temperature, was similar between heat-loading modalities at BOTOX treated and untreated sites. At the end of heat-loading (@ 0.7 °C increase in internal temperature), % CVCmax at the BOTOX treated sites (Exercise: 19 ± 2 and Passive whole-body heating: 15 ± 5 % CVCmax), were significantly less (P<0.001) than at the untreated sites (Exercise: 35 ± 4 and Passive whole-body heating: 38 ± 2 % CVCmax). Additionally, there were no differences in %CVCMax between thermal loading modalities (modality, P = 0.909; modality-by-microdialysis site interaction, P=0.230) at the end of heat-loading. Conclusions We conclude that CAVD in response to exercise heat-loading and passive whole-body heat-loading are both mediated by cholinergic nerve transmission, a critical thermoregulatory mechanism whose function appears to be independent of the thermal loading modality.

Does the iontophoretic application of bretylium tosylate modulate sweating during exercise in the heat in habitually trained and untrained men?

What is the central question of this study? Does the administration of the adrenergic presynaptic release inhibitor bretylium tosylate modulate sweating during exercise in the heat, and does this response differ between habitually trained and untrained men? What is the main finding and its importance? Iontophoretic administration of bretylium tosylate attenuates sweating during exercise in the heat in habitually trained and untrained men. However, a greater reduction occurred in trained men. The findings demonstrate a role for cutaneous adrenergic nerves in the regulation of eccrine sweating during exercise in the heat and highlight a need to advance our understanding of neural control of human eccrine sweat gland activity. We recently reported an influence of cutaneous adrenergic nerves on eccrine sweat production in habitually trained men performing an incremental exercise bout in non-heat stress conditions. Based on an assumption that increasing heat stress induces cholinergic modulation of sweating, we evaluated the hypothesis that the contribution of cutaneous adrenergic nerves on sweating would be attenuated during exercise in the heat. Twenty young habitually trained and untrained men (n=10/group) underwent three successive bouts of 15min of light-, moderate- and vigorous-intensity cycling (equivalent to 30, 50, and 70% of peak oxygen uptake ( ) respectively), each separated by a 15min recovery while wearing a perfusion suit perfused with warm water (43°C). Sweat rate (ventilated capsule) was measured continuously at two bilateral forearm skin sites treated with 10mm bretylium tosylate (an inhibitor of neurotransmitter release from adrenergic nerve terminals) and saline (control) via transdermal iontophoresis. A greater sweat rate was measured during vigorous exercise only in trained as compared to untrained men (P=0.014). In both groups, sweating was reduced at the bretylium tosylate versus control sites, albeit the magnitude of reduction was greater in the trained men (P≤0.024). These results suggest that cutaneous adrenergic nerves modulate sweating during exercise performed under a whole-body heat stress, albeit a more robust response occurs in trained men. While it is accepted that a cholinergic mechanism plays a primary role in the regulation of sweating during an exercise-heat stress, our findings highlight the need for additional studies aimed at understanding the neural control of human eccrine sweating.

No Evidence of Heat-Induced Vasoconstriction in Human Skin Using Ultrasound Doppler after Passive Whole-Body Heat Stress

No Evidence of Heat-Induced Vasoconstriction in Human Skin Using Ultrasound Doppler after Passive Whole-Body Heat Stress

Whole body heat exposure modulates acute glucose metabolism

Aim: Exercise modulates glucose tolerance and homeostasis in both healthy and diabetic individuals. Heat stress is a fundamental element of exercise. The acute glycemic response and alterations in glucose clearance following whole body passive heat stress in the absence of muscle activity has yet to be examined in humans. Knowledge of this relationship may prove useful, particularly in populations with compromised glucoregulation from reduced activity.Purpose: To determine insulin/glucose levels before and after an acute bout of heat stress in healthy, lean individuals and examine the effects of whole body heat stress (WBHS) and exercise on acute glucose tolerance in an expanded cohort.Methods: Ten subjects (24.1 ± 0.7 years) participated in a randomized control/WBHS session (up to 30 minutes at 73 °C) with fasting glucose (FG) and insulin drawn at baseline, immediately after and 30 minutes post heat stress. In the follow-up experiment, 20 anthropometrically diverse subjects (24.6 ± 2.1 years) underwent an oral glucose tolerance test (OGTT) under the conditions above.Results: FG levels rose 10% immediately following heat stress (8.6 (±5.6) mg/dl, p < .01) and returned to near baseline levels 30 minutes following WBHS. Insulin release showed its greatest increase at 30 minutes post WBHS (2.7 ± 3.5) uU/ml p < .05). WBHS resulted in a decrease in glucose uptake [AUC increased 8.2% (1430.6 ± 1957.03) mg/dl (p = .005)], particularly in nonlean individuals.Conclusion: WBHS modulates physiologic markers of metabolism. An acute bout of WBHS increases glucose and insulin levels in healthy individual and decreases glucose uptake in response to a glucose challenge, particularly those who are non-lean.

A Comparative Study of Two Ambulatory Core Temperature Assessment Methods

Background. Given the need to identify reliable non-invasive solutions for core temperature ambulatory monitoring, the purpose of this study was to evaluate the performance of zero-heat-flux (ZHF) temperature sensor on the forehead (TCOzhf) by comparing it with intestinal temperature (TCOpill) in different ambient and physiological conditions.Methods. Seven trained male subjects were followed during a 45-min rest period (STA) and a 25-min self-regulated cycling exercise performed in neutral (TMP, 22.8 °C) and hot (HOT, 38.5 °C) ambient temperature.Results.TCOzhf values differed from TCOpill of −0.23 ± 0.13 in STA, 0.15 ± 0.30 °C in TMP and 0.28±0.38 °C in HOT. The 95% limits of agreement showed an acceptable bias between TCOzhf and TCOpill in STA (±0.26 °C), but not in TMP and HOT (±0.60 and ±0.75 °C).Conclusion. The non-invasive ZHF sensor gave an accurate estimation of TCOpill in steady state but not during exercise. However, complementary results let suppose that ZHF performance is not affected by ambient conditions and could be a relevant alternative for deep body temperature measurement during whole-body heat stress.

Whole-body Heat Stress Sensitizes β1-adrenergic Receptor Mediated Cardiac Systolic Function

Whole-body Heat Stress Sensitizes β1-adrenergic Receptor Mediated Cardiac Systolic Function

Multiple Sclerosis Impairs Sweating but not Skin Blood Flow during a Passive Whole-Body Heat Stress

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS), disrupting autonomic function. PURPOSE: The aim of this study was to test the hypothesis that individuals with MS have blunted control of thermoregulatory reflex increases in sweat rate (SR), and cutaneous vasodilation compared to controls during a passive whole-body heat stress (WBH). METHODS: 18 individuals with relapsing-remitting MS and 18 healthy controls (CON) participated in the study. Core temperature (Tcore), skin temperature, heart rate, arterial blood pressure, skin blood flow (laser-Doppler flowmetry: LDF), and SR were continuously measured during normothermic baseline (34 °C water perfusing a tube-lined suit) and WBH (increased core temperature 0.8 °C via 48 °C water perfusing the suit). Following WBH, local heaters were warmed to 42 °C, inducing maximal cutaneous vasodilation at the site of LDF collection. Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to mean arterial pressure and expressed as a percentage of maximum. RESULTS: Individuals with MS had an attenuated SR response to WBH ([INCREMENT]SR from baseline: MS: 0.42±0.2 vs CON:0.60±0.3 mg/cm2/min, p=0.005), while [INCREMENT]%CVCmax was similar between the groups (CON: 41.7±16%; MS: 37.6±12 %, p=0.39). Additional analysis revealed SR responses were blunted as a function of Tcore in MS (interaction: group*Tcore, p=0.03), of which differences were evident at [INCREMENT] Tcore 0.7 °C and 0.8 °C (p<0.05). Similar analysis for [INCREMENT]%CVCmax revealed no significant interaction. CONCLUSION: Taken together, the attenuated sweat responses in MS may be a result of altered neural control of sweat rate, while the control of the cutaneous vasculature is preserved in response to a WBH.

Elevated skin and core temperatures both contribute to reductions in tolerance to a simulated haemorrhagic challenge.

What is the central question of this study? Combined increases in skin and core temperatures reduce tolerance to a simulated haemorrhagic challenge. The aim of this study was to examine the separate and combined influences of increased skin and core temperatures upon tolerance to a simulated haemorrhagic challenge. What is the main finding and its importance? Skin and core temperatures increase during many occupational settings, including military procedures, in hot environments. The study findings demonstrate that both increased skin temperature and increased core temperature can impair tolerance to a simulated haemorrhagic challenge; therefore, a soldier's tolerance to haemorrhagic injury is likely to be impaired during any military activity that results in increased skin and/or core temperatures. Tolerance to a simulated haemorrhagic insult, such as lower-body negative pressure (LBNP), is profoundly reduced when accompanied by whole-body heat stress. The aim of this study was to investigate the separate and combined influence of elevated skin (Tskin ) and core temperatures (Tcore ) on LBNP tolerance. We hypothesized that elevations in Tskin as well as Tcore would both contribute to reductions in LBNP tolerance and that the reduction in LBNP tolerance would be greatest when both Tskin and Tcore were elevated. Nine participants underwent progressive LBNP to presyncope on four occasions, as follows: (i)control, with neutral Tskin (34.3±0.5°C) and Tcore (36.8±0.2°C); (ii)primarily skin hyperthermia, with high Tskin (37.6±0.2°C) and neutral Tcore (37.1±0.2°C); (iii)primarily core hyperthermia, with neutral Tskin (35.0±0.5°C) and high Tcore (38.3±0.2°C); and (iv)combined skin and core hyperthermia, with high Tskin (38.8±0.6°C) and high Tcore (38.1±0.2°C). The LBNP tolerance was quantified via the cumulative stress index (in millimetres of mercury×minutes). The LBNP tolerance was reduced during the skin hyperthermia (569±151mmHgmin) and core hyperthermia trials (563±194 mmHgmin) relative to control conditions (1010±246mmHgmin; both P<0.05). However, LBNP tolerance did not differ between skin hyperthermia and core hyperthermia trials (P=0.92). The lowest LBNP tolerance was observed during combined skin and core hyperthermia (257±106mmHgmin; P<0.05 relative to all other trials). These data indicate that elevated skin temperature, as well as elevated core temperature, can both contribute to reductions in LBNP tolerance in heat-stressed individuals. However, heat stress-induced reductions in LBNP tolerance are greatest in conditions when both skin and core temperatures are elevated.

Cutaneous vascular &amp; sudomotor responses to heat-stress in smokers &amp; non-smokers

As approximately one billion people worldwide are chronic smokers [1] it is important to determine smokers' thermoregulatory responses to heat-stress. Although local maximal vasodilation may be attenuated in smokers [2], skin blood flow responses during whole-body heat stress are unknown. Moreover, it is unknown if sweat rate is altered in smokers; theoretically the binding of nicotine to nicotinic acetylcholine receptors [2] may initiate an earlier onset of sweating during whole-body heat stress compared to non-smokers [3]. The purpose of this study was to compare cutaneous vascular and sudomotor responses to whole-body passive heat-stress between smokers and non-smokers.

The effect of local repeated passive heating and handgrip exercise on reflex cutaneous vascular and sudomotor responses to whole-body heat stress

Enhancements in local cutaneous microvascular function are dependent upon elevations in both skin blood flow and temperature with repeated episodes of shear stress a key mechanism [1,2]. The mechanisms cause chronic sudomotor adaptations are not entirely clear however. Acute alterations in local cutaneous blood flow and temperature independently modify local sweat rate [3], possibly via variations in shear stress affecting endothelial nitric oxide release, suggesting that changes in skin blood flow and/or temperature may modulate sudomotor adaptations. It is also unclear as to the effects of localised thermal/hemodynamic interventions on neural cutaneous vascular and sudomotor responses. The aim of this study was to therefore compare the effects of repeated local forearm passive heating (that increases skin temperature and skin blood flow) and local handgrip exercise (that increases skin blood flow only) on sudomotor responses to whole-body heat stress.

Cutaneous vascular and sweating responses to intradermal administration of ATP: a role for nitric oxide synthase and cyclooxygenase?

In humans in vivo, the mechanisms behind ATP-mediated cutaneous vasodilatation along with whether and how ATP increases sweating remains uncertain. Recent work has implicated nitric oxide synthase (NOS), cyclooxygenase (COX) and/or adenosine in the modulation of cutaneous vasodilatation and sweat production during both local (i.e. localized heating) and whole-body heat stress (i.e. exercise-induced heat stress). We evaluated whether ATP-mediated cutaneous vasodilatation and sweating is mediated via NOS, COX and/or adenosine. We show that in humans in vivo, intradermal administration of ATP induces pronounced vasodilatation which is partially mediated by NOS, but neither COX nor adenosine influences ATP-mediated vasodilatation, and ATP alone does not induce an increase in sweating. These findings advance our basic physiological knowledge regarding control of skin blood flow and sweating, and provide insight into the mechanisms governing thermoeffector activity, which has major implications for whole-body heat exchange and therefore core temperature regulation in humans during heat stress. In humans in vivo, the mechanisms behind ATP-mediated cutaneous vasodilatation and whether and how ATP increases sweating remain uncertain. We evaluated whether ATP-mediated cutaneous vasodilatation and sweating is mediated via nitric oxide synthase (NOS), cyclooxygenase (COX) and/or adenosine-dependent mechanisms. Cutaneous vascular conductance (CVC, laser Doppler perfusion units/mean arterial pressure) and sweat rate (ventilated capsule) were evaluated at intradermal microdialysis forearm skin sites, each receiving pharmacological agents (two separate protocols). In Protocol 1 (n = 12), sites were perfused with: (1) lactated Ringer solution (Control), (2) 10 mm N(ω) -nitro-l-arginine (l-NNA, a NOS inhibitor), (3) 10 mm ketorolac (Ketorolac, a COX inhibitor) or (4) a combination of 10 mm l-NNA + 10 mm ketorolac (l-NNA + Ketorolac). In Protocol 2 (n = 8), sites were perfused with: (1) lactated Ringer solution (Control) or (2) 4 mm theophylline (Theophylline, an adenosine receptor inhibitor). At all sites, ATP was simultaneously perfused at 0.12, 1.2, 12, 120 and 1200 nm min(-1) (each for 20 min). Relative to CVC at the Control site with ATP infused at 120 nm min(-1) (71 ± 9% of max CVC), CVC at the Ketorolac site was comparable (64 ± 13% of max CVC, P = 0.407), but lower at l-NNA (51 ± 15% of max CVC, P = 0.040) and l-NNA + Ketorolac (51 ± 13% of max CVC, P = 0.049) sites. Conversely, across the four skin sites at any other ATP infusion rate (all P > 0.174), no differences in CVC were observed. Theophylline did not influence CVC at any ATP infusion rate (all P > 0.234). Furthermore, no ATP infusion rate elicited an increase in sweating from baseline at any skin site (all P > 0.235). We show that NOS, but neither COX nor adenosine receptors, modulates ATP-mediated cutaneous vasodilatation, whereas ATP does not directly increase sweating.

Whole‐Body Heat Stress Alters the Exercise Pressor Reflex in Humans

The effects of whole-body heat stress on sympathetic and cardiovascular responses to stimulation of muscle metaboreceptors and mechanoreceptors remain unclear. We examined the muscle sympathetic nerve activity (MSNA), renal blood velocity, blood pressure and heart rate in 14 young healthy subjects during fatiguing isometric handgrip exercise, post exercise circulatory occlusion (PECO), and passive muscle stretch during PECO. The protocol was performed under normothermic and whole-body heat stress (increase internal temperature ~0.6 °C via a heating suit) conditions. Heat stress increased the resting MSNA and heart rate. Heat stress did not alter the responses to the fatiguing exercise in mean blood pressure (MAP), heart rate and MSNA, but augmented the response in renal vascular resistance (Δ45± 6 to Δ60±8 %, P=0.04). During PECO, the increase in MAP was lower during heat stress condition than during normothemic condition (Δ20±2 vs. Δ12±1 mmHg, P<0.001), while the increases in MSNA were not different between the thermal conditions (Δ16.4±2.8 vs. Δ17.3±3.8 bursts/min, P=0.74). Under normothermic conditions, the passive stretch during PECO evoked significant increases in MAP and MSNA, while these intervention did not alter MSNA or MAP in the presence of heat stress. These data show that the pressor response to metaboreceptor stimulation is attenuated, and the MSNA response to mechanoreceptor stimulation is also attenuated in heat stress condition. These observations suggest that whole body heat stress alters exercise pressor reflex in humans.

Acetylsalicylic acid does not alter thermo-effector responses during mild whole-body passive heat stress in young men

Acetylsalicylic acid (ASA), aspirin, exerts potent systemic effects that may interfere with normal thermo-effector responses. We investigated the influence of commonly ingested ASA doses on measures of skin blood flow (SkBF) and local sweat rate (SR) during whole-body, passive heat stress. Seven male participants completed counter-balanced trials to compare ASA treatments (single dose 325 mg or 4 consecutive days 81 mg (4-d 81 mg)) to control (no ASA). Laser-Doppler flowmetry provided an index of SkBF. A ventilated capsule measured local sweat rate via capacitance hygrometry. Mean body temperature () was increased by 1 °C above baseline using a water-perfused suit. was similar at the onset of cutaneous vasodilation among trials. Cutaneous vascular conductance, expressed as a percentage change from baseline, was not different among trials. Additionally, at the onset of local SR and SR sensitivity did not differ among trials. While ASA has previously been shown to influence SkBF during heat stress, it is possible our cohort’s relatively young age may have contributed to our dissimilar results.