Human temperature regulation under heat stress in health, disease, and injury.

The human body constantly exchanges heat with the environment. Temperature regulation is a homeostatic feedback control system that ensures deep body temperature is maintained within narrow limits despite wide variations in environmental conditions and activity-related elevations in metabolic heat production. Extensive research has been performed to study the physiological regulation of deep body temperature. This review focuses on healthy and disordered human temperature regulation during heat stress. Central to this discussion is the notion that various morphological features, intrinsic factors, diseases, and injuries independently and interactively influence deep body temperature during exercise and/or exposure to hot ambient temperatures. The first sections review fundamental aspects of the human heat stress response, including the biophysical principles governing heat balance and the autonomic control of heat loss thermoeffectors. Next, we discuss the effects of different intrinsic factors (morphology, heat adaptation, biological sex, and age), diseases (neurological, cardiovascular, metabolic, and genetic), and injuries (spinal cord injury, deep burns, and heat stroke), with emphasis on the mechanisms by which these factors enhance or disturb the regulation of deep body temperature during heat stress. We conclude with key unanswered questions in this field of research.

Altered cardiac ß1 responsiveness in hyperthermic older adults.

Compared with younger adults, passive heating induced increases in cardiac output are attenuated by ∼50% in older adults. This attenuated response may be associated with older individuals' inability to maintain stroke volume through ionotropic mechanisms and/or through altered chronotropic mechanisms. The purpose of this study was to identify the interactive effect of age and hyperthermia on cardiac responsiveness to dobutamine-induced cardiac stimulation. Eleven young (26 ± 4 yr) and 8 older (68 ± 5 yr) participants underwent a normothermic and a hyperthermic (baseline core temperature +1.2°C) trial on the same day. In both thermal conditions, after baseline measurements, intravenous dobutamine was administered for 12 min at 5 µg/kg/min, followed by 12 min at 15 µg/kg/min. Primary measurements included echocardiography-based assessments of cardiac function, gastrointestinal and skin temperatures, heart rate, and mean arterial pressure. Heart rate responses to dobutamine were similar between groups in both thermal conditions (P > 0.05). The peak systolic mitral annular velocity (S'), i.e., an index of left ventricular longitudinal systolic function, was similar between groups for both thermal conditions at baseline. While normothermic, the increase in S' between groups was similar with dobutamine administration. However, while hyperthermic, the increase in S' was attenuated in the older participants with dobutamine (P < 0.001). Healthy, older individuals show attenuated inotropic, but maintained chronotropic responsiveness to dobutamine administration during hyperthermia. These data suggest that older individuals have a reduced capacity to increase cardiomyocyte contractility, estimated by changes in S', via ß1-adrenergic mechanisms while hyperthermic.

Low dose ketamine reduces pain perception and blood pressure, but not muscle sympathetic nerve activity, responses during a cold pressor test.

KEY POINTS: Low dose ketamine is a leading medication used to provide analgesia in pre-hospital and hospital settings. Low dose ketamine is increasingly used off-label to treat conditions such as depression. In animals, ketamine stimulates the sympathetic nervous system and increases blood pressure, but these physiological consequences have not been studied in conscious humans. Our data suggest that low dose ketamine administration blunts pain perception and reduces blood pressure, but not muscle sympathetic nerve activity burst frequency, responses during a cold pressor test in healthy humans. These mechanistic, physiological results inform risk-benefit analysis for clinicians administering low dose ketamine in humans. ABSTRACT: Low dose ketamine is an effective analgesic medication. However, our knowledge of the effects of ketamine on autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low dose ketamine influences autonomic cardiovascular responses during painful stimuli in humans. We tested the hypothesis that low dose ketamine blunts perceived pain, and blunts subsequent sympathetic and cardiovascular responses during an experimental noxious stimulus. Twenty-two adults (10F/12M; 27 ± 6 years; 26 ± 3 kg m-2 , mean ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed cold pressor tests (CPT; hand in ∼0.4°C ice bath for 2 min) pre- and 5 min post-drug administration (20 mg ketamine or saline). We compared pain perception (100 mm visual analogue scale), muscle sympathetic nerve activity (MSNA; microneurography, 12 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) during the pre- and post-drug CPTs separately using paired, two-tailed t tests. For the pre-drug CPT, perceived pain (P = 0.4378), MSNA burst frequency responses (P = 0.7375), and mean BP responses (P = 0.6457) were not different between trials. For the post-drug CPT, ketamine compared to placebo administration attenuated perceived pain (P < 0.0001) and mean BP responses (P = 0.0047), but did not attenuate MSNA burst frequency responses (P = 0.3662). Finally, during the post-drug CPT, there was a moderate relation between cardiac output and BP responses after placebo administration (r = 0.53, P = 0.0121), but this relation was effectively absent after ketamine administration (r = -0.12, P = 0.5885). These data suggest that low dose ketamine administration attenuates perceived pain and pressor, but not MSNA burst frequency, responses during a CPT.

Normobaric hypoxia does not alter the critical environmental limits for thermal balance during exercise-heat stress.

NEW FINDINGS: What is the central question of this study? Hypoxia reportedly does not impair thermoregulation during exercise in compensable heat stress conditions: does it have an impact on maximal heat dissipation and therefore the critical environmental limit for the physiological compensability of core temperature? What is the main finding and its importance? Although skin blood flow was higher in hypoxia, no differences in sweat rates or the critical environmental limit for the physiological compensability of core temperature - an indicator of maximal heat loss - were found compared to exercise in normoxia, indicating no influence of normobaric hypoxia on thermoregulatory capacity in warm conditions. ABSTRACT: Altered control of skin blood flow (SkBF) in hypoxia does not impair thermoregulation during exercise in compensable conditions, but its impact on maximal heat dissipation is unknown. This study therefore sought to determine whether maximum heat loss is altered by hypoxia during exercise in warm conditions. On separate days, eight males exercised for 90 min at a fixed heat production of ∼500 W in normoxia (NORM) or normobaric hypoxia (HYP, FIO2  = 0.13) in a 34°C environment. Ambient vapour pressure was maintained at 2.13 kPa for 45 min, after which it was raised 0.11 kPa every 7.5 min. The critical ambient vapour pressure at which oesophageal temperature inflected upward (Pcrit ) indicated that maximum heat dissipation had been reached. Neither local sweat rates on the upper arm, back and forehead (average NORM: 1.46 (0.15) vs. HYP: 1.41 (0.16) mg cm-2  min-1 ; P = 0.59) nor whole-body sweat losses (NORM: 1029 (137) g vs. HYP: 1025 (150) g; P = 0.95) were different between trials. Laser-Doppler flux values (LDF; arbitrary units), an index of SkBF, were not different between NORM and HYP on the forearm (P = 0.23) or back (P = 0.73); however, when normalized as a percentage of maximum, LDF values tended to be higher in HYP compared to NORM at the forearm (condition effect, P = 0.05) but not back (P = 0.19). Despite potentially greater SkBF in hypoxia, there was no difference in Pcrit between conditions (NORM: 3.67 (0.35) kPa; HYP: 3.46 (0.39) kPa; P = 0.22). These findings suggest that hypoxia does not independently alter thermoregulatory capacity during exercise in warm conditions.

Low-dose ketamine affects blood pressure, but not muscle sympathetic nerve activity, during progressive central hypovolemia without altering tolerance.

KEY POINTS: Haemorrhage is the leading cause of battlefield and civilian trauma deaths. Given that a haemorrhagic injury on the battlefield is almost always associated with pain, it is paramount that the administered pain medication does not disrupt the physiological mechanisms that are beneficial in defending against the haemorrhagic insult. Current guidelines from the US Army's Committee on Tactical Combat Casualty Care (CoTCCC) for the selection of pain medications administered to a haemorrhaging soldier are based upon limited scientific evidence, with the clear majority of supporting studies being conducted on anaesthetized animals. Specifically, the influence of low-dose ketamine, one of three analgesics employed in the pre-hospital setting by the US Army, on haemorrhagic tolerance in humans is unknown. For the first time in conscious males and females, the findings of the present study demonstrate that the administration of an analgesic dose of ketamine does not compromise tolerance to a simulated haemorrhagic insult. Increases in muscle sympathetic nerve activity during progressive lower-body negative pressure were not different between trials. Despite the lack of differences for muscle sympathetic nerve activity responses, mean blood pressure and heart rate were higher during moderate hypovolemia after ketamine vs. placebo administration. ABSTRACT: Haemorrhage is the leading cause of battlefield and civilian trauma deaths. For a haemorrhaging soldier, there are several pain medications (e.g. ketamine) recommended for use in the prehospital, field setting. However, the data to support these recommendations are primarily limited to studies in animals. Therefore, it is unknown whether ketamine adversely affects physiological mechanisms responsible for maintenance of arterial blood pressure (BP) during haemorrhage in humans. In humans, ketamine has been demonstrated to raise resting BP, although it has not been studied with the concomitant central hypovolemia that occurs during haemorrhage. Thus, the present study aimed to test the hypothesis that ketamine does not impair haemorrhagic tolerance in humans. Thirty volunteers (15 females) participated in this double-blinded, randomized, placebo-controlled trial. A pre-syncopal limited progressive lower-body negative pressure (LBNP; a validated model for simulating haemorrhage) test was conducted following the administration of ketamine (20 mg) or placebo (saline). Tolerance was quantified as a cumulative stress index and compared between trials using a paired, two-tailed t test. We compared muscle sympathetic nerve activity (MSNA; microneurography), beat-to-beat BP (photoplethysmography) and heart rate (electrocardiogram) responses during the LBNP test using a mixed effects model (time [LBNP stage] × drug). Tolerance to the LBNP test was not different between trials (Ketamine: 635 ± 391 vs. Placebo: 652 ± 360 mmHg‧min, p = 0.77). Increases in MSNA burst frequency (time: P < 0.01, trial: p = 0.27, interaction: p = 0.39) during LBNP stages were no different between trials. Despite the lack of differences for MSNA responses, mean BP (time: P < 0.01, trial: P < 0.01, interaction: p = 0.01) and heart rate (time: P < 0.01, trial: P < 0.01, interaction: P < 0.01) were higher during moderate hypovolemia after ketamine vs. placebo administration (P < 0.05 for all, post hoc), but not at the end of LBNP. These data, which are the first to be obtained in conscious humans, demonstrate that the administration of low-dose ketamine does not impair tolerance to simulated haemorrhage or mechanisms responsible for maintenance of BP.

Dietary nitrate supplementation does not influence thermoregulatory or cardiovascular strain in older individuals during severe ambient heat stress.

NEW FINDINGS: What is the central question of this study? Does dietary nitrate supplementation with beetroot juice attenuate thermoregulatory and cardiovascular strain in older adults during severe heat stress? What is the main finding and its importance? A 7-day nitrate supplementation regimen lowered resting mean arterial pressure in thermoneutral conditions. During heat stress, core and mean skin temperatures, vasodilatory responses, sweat loss, heart rate and left ventricular function were unchanged, and mean arterial pressure was only transiently reduced, post-supplementation. These data suggest nitrate supplementation with beetroot juice does not mitigate thermoregulatory or cardiovascular strain in heat-stressed older individuals. ABSTRACT: This study tested the hypothesis that dietary nitrate supplementation with concentrated beetroot juice attenuates thermoregulatory and cardiovascular strain in older individuals during environmental heat stress. Nine healthy older individuals (six females, three males; aged 67 ± 5 years) were exposed to 42.5 ± 0.1°C and 34.0 ± 0.5% relative humidity conditions for 120 min before (CON) and after 7 days of dietary nitrate supplementation with concentrated beetroot juice (BRJ; 280 ml, ∼16.8 mmol of nitrate daily). Core and skin temperatures, body mass changes (indicative of whole-body sweat loss), skin blood flow and cutaneous vascular conductance, forearm blood flow and vascular conductance, heart rate, arterial blood pressures and indices of cardiac function were measured. The 7-day beetroot juice regimen increased plasma nitrate/nitrite levels from 27.4 ± 15.2 to 477.0 ± 102.5 µmol l-1 (P < 0.01) and lowered resting mean arterial pressure from 90 ± 7 to 83 ± 10 mmHg at baseline under thermoneutral conditions (P = 0.02). However, during subsequent heat stress, no differences in core and skin temperatures, skin blood flow and vascular conductance, forearm blood flow and vascular conductance, whole-body sweat loss, heart rate, and echocardiographic indices of systolic function and diastolic filling were evident following nitrate supplementation (all P > 0.05). Mean arterial pressure was lower in BRJ vs. CON during heat stress (treatment-by-time interaction: P = 0.02). Overall, these findings suggest that dietary nitrate supplementation with concentrated beetroot juice does not attenuate thermoregulatory or cardiovascular strain in older individuals exposed to severe ambient heat stress.

Progressive exercise training improves maximal aerobic capacity in individuals with well-healed burn injuries.

Long-term rehabilitative strategies are important for individuals with well-healed burn injuries. Such information is particularly critical because patients are routinely surviving severe burn injuries given medical advances in the acute care setting. The purpose of this study was to test the hypothesis that a 6-mo community-based exercise training program will increase maximal aerobic capacity (V̇o2max) in subjects with prior burn injuries, with the extent of that increase influenced by the severity of the burn injury (i.e., percent body surface area burned). Maximal aerobic capacity (indirect calorimetry) and skeletal muscle oxidative enzyme activity (biopsy of the vastus lateralis muscle) were measured pre- and postexercise training in noninjured control subjects (n = 11) and in individuals with well-healed burn injuries (n = 13, moderate body surface area burned; n = 20, high body surface area burned). Exercise training increased V̇o2max in all groups (control: 15 ± 5%; moderate body surface area: 11 ± 3%; high body surface area: 11 ± 2%; P < 0.05), though the magnitude of this improvement did not differ between groups (P = 0.7). Exercise training also increased the activity of the skeletal muscle oxidative enzymes citrate synthase (P < 0.05) and cytochrome c oxidase (P < 0.05), an effect that did not differ between groups (P = 0.2). These data suggest that 6 mo of progressive exercise training improves V̇o2max in individuals with burn injuries and that the magnitude of body surface area burned does not lessen this adaptive response.

Folic acid supplementation does not attenuate thermoregulatory or cardiovascular strain of older adults exposed to extreme heat and humidity.

NEW FINDINGS: What is the central question of this study? Does folic acid supplementation alleviate thermoregulatory and cardiovascular strain of older adults during exposure to extreme heat and humidity? What is the main finding and its importance? Folic acid supplementation for 6 weeks did not affect whole-limb blood flow/vasodilatation, core and skin temperatures, heart rate, blood pressure and cardiac output. Thus, 6 weeks of folic acid supplementation does not alleviate thermoregulatory or cardiovascular strain of healthy older adults exposed to extreme heat and humidity. ABSTRACT: Folic acid supplementation reverses age-related reductions in cutaneous vasodilatation during passive heating. However, it is unknown if folic acid supplementation alleviates thermoregulatory and cardiovascular strain experienced by older adults during heat exposure. We evaluated the effect of folic acid supplementation on thermoregulatory and cardiovascular responses of nine healthy older adults (61-72 years, 3 males/6 females) exposed to extreme heat and humidity. Participants rested at 42°C while relative humidity was increased from 30% to 70% in 2% increments every 5 min. The protocol was performed before (CON) and after (FOLIC) 6 weeks of folic acid supplementation (5 mg day-1 ). Local cutaneous vascular conductance (CVC, laser-Doppler flowmetry), forearm vascular conductance (FVC, Doppler ultrasound), mean skin and oesophageal temperatures, heart rate, blood pressure and cardiac output were measured. Folic acid supplementation increased fasting serum folate concentrations (P < 0.01). Absolute CVC was greater throughout the protocol following supplementation (CON: 1.29 ± 0.16 units mmHg-1 vs. FOLIC: 1.65 ± 0.24 units mmHg-1 , P < 0.01). However, normalized CVC (CON: 54 ± 8% vs. FOLIC: 59 ± 7%, P = 0.22), FVC (CON: 3.47 ± 0.76 ml mmHg-1 vs. FOLIC: 3.40 ± 0.56 ml mmHg-1 , P = 0.93), mean skin (P = 0.81) and oesophageal (CON: 36.87 ± 0.28°C vs. folic: 36.90 ± 0.25°C, P = 0.98) temperatures, heart rate (CON: 83 ± 10 beats min-1 vs. FOLIC: 84 ± 8 beats min-1 , P = 0.64), blood pressure (P = 0.71) and cardiac output (P = 0.20) were unaffected by folic acid supplementation. These results demonstrate that 6 weeks of folic acid supplementation does not alleviate thermoregulatory or cardiovascular strain of healthy older adults exposed to extreme heat and humidity.

Tolerance to a haemorrhagic challenge during heat stress is improved with inspiratory resistance breathing.

NEW FINDINGS: What is the central question of this study? Does inspiratory resistance breathing improve tolerance to simulated haemorrhage in individuals with elevated internal temperatures? What is the main finding and its importance? The main finding of this study is that inspiratory resistance breathing modestly improves tolerance to a simulated progressive haemorrhagic challenge during heat stress. These findings demonstrate a scenario in which exploitation of the respiratory pump can ameliorate serious conditions related to systemic hypotension. ABSTRACT: Heat exposure impairs human blood pressure control and markedly reduces tolerance to a simulated haemorrhagic challenge. Inspiratory resistance breathing enhances blood pressure control and improves tolerance during simulated haemorrhage in normothermic individuals. However, it is unknown whether similar improvements occur with this manoeuvre in heat stress conditions. In this study, we tested the hypothesis that inspiratory resistance breathing improves tolerance to simulated haemorrhage in individuals with elevated internal temperatures. On two separate days, eight subjects performed a simulated haemorrhage challenge [lower-body negative pressure (LBNP)] to presyncope after an increase in internal temperature of 1.3 ± 0.1°C. During one trial, subjects breathed through an inspiratory impedance device set at 0 cmH2 O of resistance (Sham), whereas on a subsequent day the device was set at -7 cmH2 O of resistance (ITD). Tolerance was quantified as the cumulative stress index. Subjects were more tolerant to the LBNP challenge during the ITD protocol, as indicated by a > 30% larger cumulative stress index (Sham, 520 ± 306 mmHg min; ITD, 682 ± 324 mmHg min; P < 0.01). These data indicate that inspiratory resistance breathing modestly improves tolerance to a simulated progressive haemorrhagic challenge during heat stress.

Acute limb heating improves macro- and microvascular dilator function in the leg of aged humans.

Local heating of an extremity increases blood flow and vascular shear stress throughout the arterial tree. Local heating acutely improves macrovascular dilator function in the upper limbs of young healthy adults through a shear stress-dependent mechanism but has no such effect in the lower limbs of this age group. The effect of acute limb heating on dilator function within the atherosclerotic prone vasculature of the lower limbs of aged adults is unknown. Therefore, the purpose of this study was to test the hypothesis that acute lower limb heating improves macro- and microvascular dilator function within the leg vasculature of aged adults. Nine young and nine aged adults immersed their lower limbs at a depth of ~33 cm into a heated (~42°C) circulated water bath for 45 min. Before and 30 min after heating, macro (flow-mediated dilation)- and microvascular (reactive hyperemia) dilator functions were assessed in the lower limb, following 5 min of arterial occlusion, via Doppler ultrasound. Compared with preheat, macrovascular dilator function was unchanged following heating in young adults (P = 0.6) but was improved in aged adults (P = 0.04). Similarly, microvascular dilator function, as assessed by peak reactive hyperemia, was unchanged following heating in young adults (P = 0.1) but was improved in aged adults (P < 0.01). Taken together, these data suggest that acute lower limb heating improves both macro- and microvascular dilator function in an age dependent manner. NEW & NOTEWORTHY: We demonstrate that lower limb heating acutely improves macro- and microvascular dilator function within the atherosclerotic prone vasculature of the leg in aged adults. These findings provide evidence for a potential therapeutic use of chronic lower limb heating to improve vascular health in primary aging and various disease conditions.

Folic acid ingestion improves skeletal muscle blood flow during graded handgrip and plantar flexion exercise in aged humans.

Skeletal muscle blood flow is attenuated in aged humans performing dynamic exercise, which is due, in part, to impaired local vasodilatory mechanisms. Recent evidence suggests that folic acid improves cutaneous vasodilation during localized and whole body heating through nitric oxide-dependent mechanisms. However, it is unclear whether folic acid improves vasodilation in other vascular beds during conditions of increased metabolism (i.e., exercise). The purpose of this study was to test the hypothesis that folic acid ingestion improves skeletal muscle blood flow in aged adults performing graded handgrip and plantar flexion exercise via increased vascular conductance. Nine healthy, aged adults (two men and seven women; age: 68 ± 5 yr) performed graded handgrip and plantar flexion exercise before (control), 2 h after (acute, 5 mg), and after 6 wk (chronic, 5 mg/day) folic acid ingestion. Forearm (brachial artery) and leg (superficial femoral artery) blood velocity and diameter were measured via Duplex ultrasonography and used to calculate blood flow. Acute and chronic folic acid ingestion increased serum folate (both P < 0.05 vs. control). During handgrip exercise, acute and chronic folic acid ingestion increased forearm blood flow (both conditions P < 0.05 vs. control) and vascular conductance (both P < 0.05 vs. control). During plantar flexion exercise, acute and chronic folic acid ingestion increased leg blood flow (both P < 0.05 vs. control), but only acute folic acid ingestion increased vascular conductance (P < 0.05 vs. control). Taken together, folic acid ingestion increases blood flow to active skeletal muscle primarily via improved local vasodilation in aged adults.NEW & NOTEWORTHY Our findings demonstrate that folic acid ingestion improves blood flow via enhanced vascular conductance in the exercising skeletal muscle of aged humans. These findings provide evidence for the therapeutic use of folic acid to improve skeletal muscle blood flow, and perhaps exercise and functional capacity, in human primary aging.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/folic-acid-and-exercise-hyperemia-in-aging/.

Effect of increases in cardiac contractility on cerebral blood flow in humans.

The effect of acute increases in cardiac contractility on cerebral blood flow (CBF) remains unknown. We hypothesized that the external carotid artery (ECA) downstream vasculature modifies the direct influence of acute increases in heart rate and cardiac function on CBF regulation. Twelve healthy subjects received two infusions of dobutamine [first a low dose (5 µg·kg-1·min-1) and then a high dose (15 µg·kg-1·min-1)] for 12 min each. Cardiac output, blood flow through the internal carotid artery (ICA) and ECA, and echocardiographic measurements were performed during dobutamine infusions. Despite increases in cardiac contractility, cardiac output, and arterial pressure with dobutamine, ICA blood flow and conductance slightly decreased from resting baseline during both low- and high-dose infusions. In contrast, ECA blood flow and conductance increased appreciably during both low- and high-dose infusions. Greater ECA vascular conductance and corresponding increases in blood flow may protect overperfusion of intracranial cerebral arteries during enhanced cardiac contractility and associated increases in cardiac output and perfusion pressure. Importantly, these findings suggest that the acute increase of blood perfusion attributable to dobutamine administration does not cause cerebral overperfusion or an associated risk of cerebral vascular damage.NEW & NOTEWORTHY A dobutamine-induced increase in cardiac contractility did not increase internal carotid artery blood flow despite an increase in cardiac output and arterial blood pressure. In contrast, external carotid artery blood flow and conductance increased. This external cerebral blood flow response may assist with protecting from overperfusion of intracranial blood flow.

Does attenuated skin blood flow lower sweat rate and the critical environmental limit for heat balance during severe heat exposure?

NEW FINDINGS: What is the central question of this study? Does attenuated skin blood flow diminish sweating and reduce the critical environmental limit for heat balance, which indicates maximal heat loss potential, during severe heat stress? What is the main finding and its importance? Isosmotic hypovolaemia attenuated skin blood flow by ∼20% but did not result in different sweating rates, mean skin temperatures or critical environmental limits for heat balance compared with control and volume-infusion treatments, suggesting that the lower levels of skin blood flow commonly observed in aged and diseased populations may not diminish maximal whole-body heat dissipation. Attenuated skin blood flow (SkBF) is often assumed to impair core temperature (Tc ) regulation. Profound pharmacologically induced reductions in SkBF (∼85%) lead to impaired sweating, but whether the smaller attenuations in SkBF (∼20%) more often associated with ageing and certain diseases lead to decrements in sweating and maximal heat loss potential is unknown. Seven healthy men (28 ± 4 years old) completed a 30 min equilibration period at 41°C and a vapour pressure (Pa ) of 2.57 kPa followed by incremental steps in Pa of 0.17 kPa every 6 min to 5.95 kPa. Differences in heat loss potential were assessed by identifying the critical vapour pressure (Pcrit ) at which an upward inflection in Tc occurred. The following three separate treatments elicited changes in plasma volume to achieve three distinct levels of SkBF: control (CON); diuretic-induced isosmotic dehydration to lower SkBF (DEH); and continuous saline infusion to maintain SkBF (SAL). The Tc , mean skin temperature (Tsk ), heart rate, mean laser-Doppler flux (forearm and thigh; LDFmean ), mean local sweat rate (forearm and thigh; LSRmean ) and metabolic rate were measured. In DEH, a 14.2 ± 5.7% lower plasma volume resulted in a ∼20% lower LDFmean in perfusion units (PU) (DEH, 139 ± 23 PU; CON, 176 ± 22 PU; and SAL, 186 ± 22 PU; P = 0.034). However, LSRmean and whole-body sweat losses were unaffected by treatment throughout (P > 0.482). The Pcrit for Tc was similar between treatments (CON, 5.05 ± 0.30 kPa; DEH, 4.93 ± 0.16 kPa; and SAL, 5.12 ± 0.10 kPa; P = 0.166). Furthermore, no differences were observed in the skin-air temperature gradient, metabolic rate or changes in Tc (P > 0.197). In conclusion, a ∼20% reduction in SkBF alters neither sweat rate nor the upper limit for heat loss from the skin during non-encapsulated passive heat stress.

Do greater rates of body heat storage precede the accelerated reduction of self-paced exercise intensity in the heat?

AIM: To reevaluate the previous hypothesis that greater reductions in self-paced exercise intensity in the heat are mediated by early differences in the rate of body heat storage (S). METHODS: Eight trained volunteers cycled in 19 °C/1.8 kPa (COOL), 25 °C/1.2 kPa (NORM), and 34 °C/1.6 kPa (HOT), while maintaining an RPE of 16. Potential differences in S following the onset of exercise were assessed by comparing rates of esophageal temperature change (ΔT es/Δt); and estimated S values using a traditional two-compartment thermometric model (S therm) of changes in rectal (T re) and skin (T sk) temperature, and partitional calorimetry (S cal). RESULTS: After 15 min of exercise, workload decreased more in HOT vs. COOL (P = 0.03), resulting in a shorter time (HOT: 40.7 ± 14.9 min; COOL: 53.5 ± 18.7 min; P = 0.04) to 70 % of initial workload. However, there were no preceding differences in ΔT es/Δt between conditions (P = 0.18). S therm values were different between HOT and COOL during the first 5 min of exercise (P < 0.05), primarily due to negative S therm values (-32 ± 15 kJ min(-1)) in COOL, which according to partitional calorimetric measurements, required improbably high (~56 kJ min(-1)) rates of evaporation when no sweating on the back and thigh was observed until after 7.6 ± 1.5 min and 4.8 ± 1.7 min of exercise, respectively. S cal values in the first 5 min of exercise confirmed S was actually positive in COOL (+21 ± 8 kJ min(-1)) and not negative. Different S therm values following the onset of exercise at different environmental temperatures are simply due to transient differences in the rate of change in T sk. CONCLUSION: Reductions in self-paced exercise intensity in the heat are not mediated by early differences in S following the onset of exercise.

Burn size and environmental conditions modify thermoregulatory responses to exercise in burn survivors.

This project tested the hypothesis that burn survivors can perform mild/moderate-intensity exercise in temperate and hot environments without excessive elevations in core body temperature. Burn survivors with low (23 ± 5%TBSA; N = 11), moderate (40 ± 5%TBSA; N = 9), and high (60 ± 8%TBSA; N = 9) burn injuries performed 60 minutes of cycle ergometry exercise (72 ± 15 watts) in a 25°C and 23% relative humidity environment (ie, temperate) and in a 40°C and 21% relative humidity environment (ie, hot). Absolute gastrointestinal temperatures (TGI) and changes in TGI (ΔTGI) were obtained. Participants with an absolute TGI of >38.5°C and/or a ΔTGI of >1.5°C were categorized as being at risk for hyperthermia. For the temperate environment, exercise increased ΔTGI in all groups (low: 0.72 ± 0.21°C, moderate: 0.42 ± 0.22°C, and high: 0.77 ± 0.25°C; all P < .01 from pre-exercise baselines), resulting in similar absolute end-exercise TGI values (P = .19). Importantly, no participant was categorized as being at risk for hyperthermia, based upon the aforementioned criteria. For the hot environment, ΔTGI at the end of the exercise bout was greater for the high group when compared to the low group (P = .049). Notably, 33% of the moderate cohort and 56% of the high cohort reached or exceeded a core temperature of 38.5°C, while none in the low cohort exceeded this threshold. These data suggest that individuals with a substantial %TBSA burned can perform mild/moderate intensity exercise for 60 minutes in temperate environmental conditions without risk of excessive elevations in TGI. Conversely, the risk of excessive elevations in TGI during mild/moderate intensity exercise in a hot environment increases with the %TBSA burned.

Inhibiting regional sweat evaporation modifies the ventilatory response to exercise: interactions between core and skin temperature.

In humans, elevated body temperatures can markedly increase the ventilatory response to exercise. However, the impact of changing the effective body surface area (BSA) for sweat evaporation (BSAeff) on such responses is unclear. Ten healthy adults (9 males, 1 female) performed eight exercise trials cycling at 6 W/kg of metabolic heat production for 60 min. Four conditions were used where BSAeff corresponded to 100%, 80%, 60%, and 40% of BSA using vapor-impermeable material. Four trials (one at each BSAeff) were performed at 25°C air temperature, and four trials (one at each BSAeff) at 40°C air temperature, each with 20% humidity. The slope of the relation between minute ventilation and carbon dioxide elimination (V̇E/V̇co2 slope) assessed the ventilatory response. At 25°C, the V̇E/V̇co2 slope was elevated by 1.9 and 2.6 units when decreasing BSAeff from 100 to 80 and to 40% (P = 0.033 and 0.004, respectively). At 40°C, V̇E/V̇co2 slope was elevated by 3.3 and 4.7 units, when decreasing BSAeff from 100 to 60 and to 40% (P = 0.016 and P < 0.001, respectively). Linear regression analyses using group average data from each condition demonstrated that end-exercise mean body temperature (integration of core and mean skin temperature) was better associated with the end-exercise ventilatory response, compared with core temperature alone. Overall, we show that impeding regional sweat evaporation increases the ventilatory response to exercise in temperate and hot environmental conditions, and the effect is mediated primarily by increases in mean body temperature.NEW & NOTEWORTHY Exercise in the heat increases the slope of the relation between minute ventilation and carbon dioxide elimination (V̇E/V̇co2 slope) in young healthy adults. An indispensable role for skin temperature in modulating the ventilatory response to exercise is noted, contradicting common belief that internal/core temperature acts independently as a controller of ventilation during hyperthermia.

Attrition of Well-Healed Burn Survivors to a 6-Month Community-Based Exercise Program: A Retrospective Evaluation.

The purpose of this study was to evaluate whether burn survivors have lower adherence compared to non-burned control individuals during a 6-month community-based exercise program. In burn survivors, we sought to answer if there was a relation between the size of the burn injury and dropout frequency. Fifty-two burn survivors and 15 non-burned controls (n = 67) were recruited for a 6-month community-based (ie, non-supervised), progressive, exercise training program. During the exercise program, 27% (ie, 4 of the 15 enrolled) of the non-burned individuals dropped out of the study, while 37% (ie, 19 of the 52) of the burn survivors dropped out from the study. There was no difference in the percentage of individuals who dropped out between groups (P = .552). There was no difference in size of the burn injury, expressed as percent body surface area burned (%BSA) between the burn survivors that dropped out versus those who completed the exercise regimen (P = .951). We did not observe a relation between %BSA burned and dropouts (log odds = -0.15-0.01(%BSA), B = -0.01, SE = 0.015, P = .541). There was no effect of %BSA burned on the probability of dropout [Exp (B) = 0.991, 95% CI (0.961, 1.020)] and there were no differences in the percentage of individuals who dropped out of the study based on %BSA burned (χ2(1) = 0.44, P = .51). These data demonstrate that burn survivors have similar exercise adherence relative to a non-burned group and the extent of a burn injury does not affect exercise program adherence.

Six Months of Exercise Training Improves Ventilatory Responses during Exercise in Adults with Well-Healed Burn Injuries.

INTRODUCTION: Pulmonary function is lower after a severe burn injury, which could influence ventilatory responses during exercise. It is unclear whether exercise training improves pulmonary function or ventilatory responses during exercise in adults with well-healed burn injuries. Therefore, we tested the hypothesis that exercise training improves pulmonary function and ventilatory responses during exercise in adults with well-healed burn injuries. METHODS: Thirty-nine adults (28 with well-healed burn injuries and 11 non-burn-injured controls) completed 6 months of unsupervised, progressive exercise training including endurance, resistance, and high-intensity interval components. Before and after exercise training, we performed comprehensive pulmonary function testing and measured ventilatory responses during cycling exercise. We compared variables using two-way ANOVA (group-time; i.e., preexercise/postexercise training (repeated factor)). RESULTS: Exercise training did not increase percent predicted spirometry, lung diffusing capacity, or airway resistance measures (time: P ≥ 0.14 for all variables). However, exercise training reduced minute ventilation ( V̇E ; time: P ≤ 0.05 for 50 and 75 W) and the ventilatory equivalent for oxygen ( V̇E /V̇O 2 ; time: P < 0.001 for 75 W) during fixed-load exercise for both groups. The ventilatory equivalent for carbon dioxide ( V̇E /V̇CO 2 ) during exercise at 75 W was reduced after exercise training (time: P = 0.04). The percentage of age-predicted maximum heart rate at the ventilatory threshold was lower in adults with well-healed burn injuries before ( P = 0.002), but not after ( P = 0.22), exercise training. Lastly, exercise training increased V̇E and reduced V̇E /V̇O 2 during maximal exercise (time: P = 0.005 for both variables). CONCLUSIONS: These novel findings demonstrate that exercise training can improve ventilatory responses during exercise in adults with well-healed burn injuries.

Cardiac remodeling in well-healed burn survivors after 6 months of unsupervised progressive exercise training.

Aerobic exercise is important in the rehabilitation of individuals with prior burn injuries, but no studies have examined whether adult burn survivors demonstrate cardiac remodeling to long-term aerobic exercise training. In this study, we tested the hypothesis that 6 months of progressive exercise training improves cardiac magnetic resonance imaging-based measures of cardiac structure and function in well-healed burn survivors. Secondary analyses explored relations between burn surface area and changes in cardiac structure in the cohort of burn survivors. V̇o2peak assessments and cardiac magnetic resonance imaging were performed at baseline and following 6 months of progressive exercise training from 19 well-healed burn survivors and 10 nonburned control participants. V̇o2peak increased following 6 months of training in both groups (Control: Δ5.5 ± 5.8 mL/kg/min; Burn Survivors: Δ3.2 ± 3.6 mL/kg/min, main effect of training, P < 0.001). Left ventricle (LV) mass (Control: Δ1.7 ± 3.1 g/m2; Burn survivors: Δ1.8 ± 2.7 g/m2), stroke volume (Control: Δ5.8 ± 5.2 mL/m2; Burn Survivors: Δ2.8 ± 4.2 mL/m2), and ejection fraction (Control: Δ2.4 ± 4.0%; Burn Survivors: Δ2.2 ± 4.3%) similarly increased following 6 months of exercise training in both cohorts (main effect of training P < 0.05 for all indexes). LV end-diastolic volume increased in the control group (Δ6.5 ± 4.5 mL/m2) but not in the cohort of burn survivors (Δ1.9 ± 2.7 mL/m2, interaction, P = 0.040). Multiple linear regression analyses revealed that burn surface area had little to no effect on changes in ventricular mass or end-diastolic volumes in response to exercise training. Our findings provide initial evidence of physiological cardiac remodeling, which is not impacted by burn size, in response to exercise training in individuals with well-healed burn injuries.NEW & NOTEWORTHY Aerobic exercise is important in the rehabilitation of individuals with prior burn injuries, but no studies have examined whether adult burn survivors demonstrate cardiac remodeling to long-term aerobic exercise training. In this study, we tested the hypothesis that 6 months of progressive exercise training would improve cardiac magnetic resonance imaging-based measures of cardiac structure and function in well-healed burn survivors. Our findings highlight the ability of exercise training to modify cardiac structure and function in well-healed burn survivors and nonburned sedentary controls alike.

Compensatory hyperhidrosis following thoracic sympathectomy: a biophysical rationale.

A side-effect of endoscopic thoracic sympathectomy (ETS) is compensatory hyperhidrosis (CH), characterized by excessive sweating from skin areas with intact sudomotor function. The physiological mechanism of CH is unknown, but may represent an augmented local sweat rate from skin areas with uninterrupted sympathetic innervation based on evaporative heat balance requirements. For a given combination of activity and climate, the same absolute amount of evaporation (if any) is needed to balance the rate of metabolic heat production both pre- and post-ETS. However, the rate of local sweating per unit of skin surface area with intact sudomotor activity must be greater post-ETS as evaporation must be derived from a smaller skin surface area. Under conditions with high evaporative requirements, greater degradations in sweating efficiency associated with an increased dripping of sweat should also occur post-ETS, further pronouncing the sweat rate required for heat balance. In conclusion, in addition to the potential role of psychological stimuli for increased sudomotor activity, the existence of CH post-ETS can be described by the interplay between fundamental thermoregulatory physiology and altered heat balance biophysics and does not require a postoperative alteration in physiological control.