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.

The Effect of Heat Exposure on Myocardial Blood Flow and Cardiovascular Function.

BACKGROUND: Heat extremes are associated with greater risk for cardiovascular death. The pathophysiologic mechanisms mediating this association are unknown. OBJECTIVE: To quantify the myocardial blood flow (MBF) requirements of heat exposure. DESIGN: Experimental study. (ClinicalTrials.gov: NCT04549974). SETTING: Laboratory-based. PARTICIPANTS: 61 participants, comprising 20 healthy young adults (mean age, 28 years), 21 healthy older adults (mean age, 67 years), and 20 older adults with coronary artery disease (CAD) (mean age, 70 years). INTERVENTION: Participants were heated until their core temperature increased 1.5 °C; MBF was measured before heat exposure and at every increase of 0.5 °C in core temperature. MEASUREMENTS: The primary outcome was MBF measured by positron emission tomography-computed tomography. Secondary outcomes included heart rate, blood pressure, and body weight change. RESULTS: At a core temperature increase of 1.5 °C, MBF increased in healthy young adults (change, 0.8 mL/min/g [95% CI, 0.5 to 1.0 mL/min/g]), healthy older adults (change, 0.7 mL/min/g [CI, 0.5 to 0.9 mL/min/g]), and older adults with CAD (change, 0.6 mL/min/g [CI, 0.3 to 0.8 mL/min/g]). This represented a 2.08-fold (CI, 1.75- to 2.41-fold), 1.79-fold (CI, 1.59- to 1.98-fold), and 1.64-fold (CI, 1.41- to 1.87-fold) change, respectively, from preexposure values. Imaging evidence of asymptomatic heat-induced myocardial ischemia was seen in 7 adults with CAD (35%) in post hoc analyses. LIMITATIONS: In this laboratory-based study, heating was limited to about 100 minutes and participants were restricted in movement and fluid intake. Participants refrained from strenuous exercise and smoking; stopped alcohol and caffeine intake; and withheld ß-blockers, calcium-channel blockers, and nitroglycerin before heating. CONCLUSION: Heat exposure that increases core temperature by 1.5 °C nearly doubles MBF. Changes in MBF did not differ by age or presence of CAD, but some older adults with CAD may experience asymptomatic myocardial ischemia. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Shifting focus: Time to look beyond the classic physiological adaptations associated with human heat acclimation.

Planet Earth is warming at an unprecedented rate and our future is now assured to be shaped by the consequences of more frequent hot days and extreme heat. Humans will need to adapt both behaviorally and physiologically to thrive in a hotter climate. From a physiological perspective, countless studies have shown that human heat acclimation increases thermoeffector output (i.e., sweating and skin blood flow) and lowers cardiovascular strain (i.e., heart rate) during heat stress. However, the mechanisms mediating these adaptations remain understudied. Furthermore, several possible benefits of heat acclimation for other systems and functions involved in maintaining health and performance during heat stress remain to be elucidated. This review summarizes recent advances in human heat acclimation, with emphasis on recent studies that (1) advanced our understanding of the mechanisms mediating improved thermoeffector output and (2) investigated adaptations that go beyond those classically associated with heat acclimation. We highlight that these studies have contributed to a better understanding of the integrated physiological responses underlying human heat acclimation while leaving key unanswered questions that will need to be addressed in the future.

Work-rest regimens for work in hot environments: A scoping review.

BACKGROUND: To limit exposures to occupational heat stress, leading occupational health and safety organizations recommend work-rest regimens to prevent core temperature from exceeding 38°C or increasing by ≥1°C. This scoping review aims to map existing knowledge of the effects of work-rest regimens in hot environments and to propose recommendations for future research based on identified gaps. METHODS: We performed a search of 10 databases to retrieve studies focused on work-rest regimens under hot conditions. RESULTS: Forty-nine articles were included, of which 35 were experimental studies. Most studies were conducted in laboratory settings, in North America (71%), on healthy young adults, with 94% of the 642 participants being males. Most studies (66%) employed a protocol duration ≤240 min (222 ± 162 min, range: 37-660) and the time-weighted average wet-bulb globe temperature was 27 ± 4°C (range: 18-34). The work-rest regimens implemented were those proposed by the American Conference of Governmental and Industrial Hygiene (20%), National Institute of Occupational Safety and Health (11%), or the Australian Army (3%). The remaining studies (66%) did not mention how the work-rest regimens were derived. Most studies (89%) focused on physical tasks only. Most studies (94%) reported core temperature, whereas only 22% reported physical and/or mental performance outcomes, respectively. Of the 35 experimental studies included, 77% indicated that core temperature exceeded 38°C. CONCLUSIONS: Although work-rest regimens are widely used, few studies have investigated their physiological effectiveness. These studies were mainly short in duration, involved mostly healthy young males, and rarely considered the effect of work-rest regimens beyond heat strain during physical exertion.

Impact of passive heat stress and passive heat acclimation on circulating extracellular vesicles: An exploratory analysis.

NEW FINDINGS: What is the central question of this study? How does passive heat stress and subsequent heat acclimation affect the circulating concentration of extracellular vesicles? What is the main finding and its importance? Passive heat stress increased the circulating concentration of total and platelet extracellular vesicles. Seven days of hot water immersion did not modify the change in circulating concentrations of extracellular vesicles during passive heat stress. ABSTRACT: This retrospective exploratory analysis aimed to improve our understanding of the effect of passive heat stress and subsequent heat acclimation on the circulating concentration of extracellular vesicles (EVs). Healthy young adults (four females and six males, 25 ± 4 years of age, 1.72 ± 0.08 m in height and weighing 71.6 ± 9.0 kg) were heated with a water-perfused suit before and after seven consecutive days of hot water immersion. Pre-acclimation, participants were heated until oesophageal temperature increased to ∼1.4°C above baseline values. Post-acclimation, participants were heated until oesophageal temperature reached the same absolute value as the pre-acclimation visit (∼38.2°C). Venous blood samples were obtained before and at the end of passive heating to quantify plasma concentrations of EVs from all cell types (CSFE+ ), all cell types except erythrocytes (CSFE+ MHCI+ ), platelets (CSFE+ MHCI+ CD41+ ), endothelial cells (CSFE+ MHCI+ CD62e+ ), red blood cells (CSFE+ CD235a+ ) and leucocytes (CSFE+ MHCI+ CD45+ ) via flow cytometry. Passive heat stress increased the concentration of CFSE+ EVs (46,150,000/ml [3,620,784, 88,679,216], P = 0.036), CFSE+ MHCI+ EVs (28,787,500/ml [9,851,127, 47,723,873], P = 0.021) and CSFE+ MHCI+ CD41+ EVs (28,343,500/ml [9,637,432, 47,049,568], P = 0.008). The concentration of CSFE+ MHCI+ CD62e+ EVs (94,230/ml [-55,099, 243,559], P = 0.187), CSFE+ CD235a+ EVs (-1,414/ml [-15,709, 12,882], P = 0.403) or CSFE+ MHCI+ CD45+ EVs (-192,915/ml [-690,166, 304,336], P = 0.828) did not differ during heat stress. The change in circulating EVs during passive heat stress did not differ after heat acclimation (thermal state × acclimation interactions, all P ≥ 0.180). These results demonstrate that passive heat stress increases the circulating concentration of total and platelet EVs and that passive heat acclimation does not alter this increase.

The acute effect of heat exposure on forearm macro- and microvascular function: Impact of measurement timing, heating modality and biological sex.

NEW FINDINGS: What is the central question of this study? Do measurement timing, heating modality and biological sex modulate the acute effect of heat exposure on brachial artery flow-mediated dilatation and postocclusion reactive hyperaemia? What is the main finding and its importance? The acute effect of heat exposure on brachial artery flow-mediated dilatation and postocclusion reactive hyperaemia is: (1) transient and short lasting; (2) different between forearm and whole-body heating; (3) unaffected by forearm heating during whole-body heating; and (4) not different but not always equivalent between males and females. These findings provide a useful basis for future studies to investigate the acute effect of heat exposure on vascular function. ABSTRACT: The aim of this study was to gain a better understanding of the acute effect of heat exposure on brachial artery flow-mediated dilatation (FMD) and postocclusion reactive hyperaemia (PORH) by: characterizing the time course of changes post-heating; comparing forearm and whole-body heating; determining the impact of forearm heating during whole-body heating; and comparing males and females. Twenty adults (11 males and nine females; 28 ± 6 years of age) underwent two forearm [10 min electric blanket (EB) or 30 min hot water immersion (WI)] and two whole-body [60 min water-perfused suit with forearm covered (WBH-C) or uncovered (WBH-U)] heating modalities. The FMD and PORH were measured before and after (≤5, 30, 60, 90 and 120 min) heating. The FMD increased from baseline 30 min after EB, and 30 and 90 min after WI. In contrast, FMD decreased from baseline immediately after both WBH modalities. Peak PORH increased immediately after WI and both WBH modalities. Total PORH did not differ after WI, whereas it decreased immediately after both WBH modalities. Covering the forearm during WBH did not alter acute changes in FMD or PORH. Changes in FMD and PORH did not differ statistically between males and females during each heating modality, although the observed differences could not always be considered equivalent. These results demonstrate that the acute effect of heat exposure on brachial artery FMD and PORH is: (1) transient and short lasting; (2) different between forearm heating and WBH; (3) unaffected by direct forearm heating during WBH; and (4) not different but not always equivalent between males and females.

Control of blood pressure in the cold: differentiation of skin and skeletal muscle vascular resistance.

NEW FINDINGS: What is the central question of this study? Why does blood pressure increases during cold air exposure? Specifically, what is the contribution of skin and skeletal muscle vascular resistance during whole body versus isolated face cooling? What is the main finding and its importance? Whole-body cooling caused an increase in blood pressure through an increase in skeletal muscle and cutaneous vascular resistance. However, isolated mild face cooling caused an increase in blood pressure predominately via an increase in cutaneous vasoconstriction. ABSTRACT: The primary aim of this investigation was to determine the individual contribution of the cutaneous and skeletal muscle circulations to the cold-induced pressor response. To address this, we examined local vascular resistances in the cutaneous and skeletal muscle of the arm and leg. Thirty-four healthy individuals underwent three different protocols, whereby cold air to clamp skin temperature (27°C) was passed over (1) the whole-body, (2) the whole-body, but with the forearm pre-cooled to clamp cutaneous vascular resistance, and (3) the face. Cold exposure applied to the whole body or isolated to the face increased mean arterial pressure (all, P < 0.001) and total peripheral resistance (all, P < 0.047) compared to thermal neutral baseline. Whole-body cooling increased femoral (P < 0.005) and brachial artery resistance (P < 0.003) compared to thermoneutral baseline. Moreover, when the forearm was pre-cooled to remove the contribution of cutaneous resistance (P = 0.991), there was a further increase in lower arm vasoconstriction (P = 0.036) when whole-body cooling was superimposed. Face cooling also caused a reflex increase in lower arm cutaneous (P = 0.009) and brachial resistance (P = 0.050), yet there was no change in femoral resistance (P = 0.815) despite a reflex increase in leg cutaneous resistance (P = 0.010). Cold stress causes an increase in blood pressure through a change in total peripheral resistance that is largely due to cutaneous vasoconstriction with face cooling, but there is additional vasoconstriction in the skeletal muscle vasculature with whole-body cooling.

Cardiovascular control during heat stress in older adults: time for an update.

It is generally accepted that older adults display an impaired cardiovascular response to heat stress, and it has been suggested that this impaired response contributes to their increased risk of mortality during extreme heat events. Seminal studies have shown that cutaneous vasodilation, the redistribution of blood flow from visceral organs, and the increase in cardiac output are blunted in older adults during passive heating. The blunted rise of cardiac output was initially attributed to an inability to maintain stroke volume, suggesting that cardiac systolic and/or diastolic function does not adequately respond to the constraints of heat stress in older adults. Recent studies evaluated potential mechanisms underlying these seminal findings and their results challenge some of these initial observations. Notably, stroke volume is maintained during heat exposure in older adults and studies have provided evidence for preserved cardiac systolic and diastolic functions in this population. Nonetheless, a blunted increase in cardiac output during heat exposure remains a consistent observation in older adults, although it is now attributed to a blunted increase in heart rate. Recent studies have also evaluated the possibility that the attenuated capacity of aged skin to vasodilate contributes to a blunted increase in cardiac output during heat stress. The objective of this Mini-Review is to highlight these recent advances and challenge the long-standing view that the control of stroke volume during heat exposure is compromised in older adults. By doing so, our intent is to stimulate future studies to evaluate several unanswered questions in this area of research.

Revisiting the evaluation of central versus peripheral thermoregulatory control in humans.

Human thermoregulatory control is often evaluated through the relationship between thermoeffector output and core or mean body temperature. In addition to providing a general indication of whether a variable of interest alters thermoregulatory control, this relationship is often used to determine how this alteration may occur. This latter interpretation relies upon two parameters of the thermoeffector output-body temperature relationship: the onset threshold and thermosensitivity. Traditionally, changes in the onset threshold and thermosensitivity are interpreted as "central" or "peripheral" modulation of thermoregulatory control, respectively. This mini-review revisits the origins of the thermoeffector output-body temperature relationship and its use to interpret "central" or "peripheral" modulation of thermoregulatory control. Against this background, we discuss the strengths and weaknesses of this approach and highlight that "central" thermoregulatory control reflects the neural control of body temperature whereas "peripheral" thermoregulatory control reflects properties specific to the thermoeffector organs. We highlight studies that employed more direct approaches to investigate the neural control of body temperature and peripheral properties of thermoeffector organs. We conclude by encouraging future investigations interested in studying thermoregulatory control to more directly investigate the component of the thermoeffector loop under investigation.heat; human; skin blood flow; sweat; thermoregulatory.

A retrospective analysis to determine if exercise training-induced thermoregulatory adaptations are mediated by increased fitness or heat acclimation.

NEW FINDINGS: What is the central question of this study? Are fitness-related improvements in thermoregulatory responses during uncompensable heat stress mediated by aerobic capacity V̇O2max or is it the partial heat acclimation associated with training? What is the main finding and its importance? During uncompensable heat stress, individuals with high and low V̇O2max displayed similar sweating and core temperature responses whereas exercise training in previously untrained individuals resulted in a greater sweat rate and a smaller rise in core temperature. These observations suggest that it is training, not V̇O2max per se, that mediates thermoregulatory improvements during uncompensable heat stress. ABSTRACT: It remains unclear whether aerobic fitness, as defined by the maximum rate of oxygen consumption V̇O2max , independently improves heat dissipation in uncompensable environments, or whether the thermoregulatory adaptations associated with heat acclimation are due to repeated bouts of exercise-induced heat stress during regular aerobic training. The present analysis sought to determine if V̇O2max independently influences thermoregulatory sweating, maximum skin wettedness (ωmax ) and the change in rectal temperature (ΔTre ) during 60 min of exercise in an uncompensable environment (37.0 ± 0.8°C, 4.0 ± 0.2 kPa, 64 ± 3% relative humidity) at a fixed rate of heat production per unit mass (6 W kg-1 ). Retrospective analyses were performed on 22 participants (3 groups), aerobically unfit (UF; n = 7; V̇O2max : 41.7 ± 9.4 ml kg-1  min-1 ), aerobically fit (F; n = 7; V̇O2max : 55.6 ± 4.3 ml kg-1  min-1 ; P < 0.01) and aerobically unfit (n = 8) individuals, before (pre; V̇O2max : 45.8 ± 11.6 ml kg-1  min-1 ) and after (post; V̇O2max : 52.0 ± 11.1 ml kg-1  min-1 ; P < 0.001) an 8-week training intervention. ωmax was similar between UF (0.74 ± 0.09) and F (0.78 ± 0.08, P = 0.22). However, ωmax was greater post- (0.84 ± 0.08) compared to pre- (0.72 ± 0.06, P = 0.02) training. During exercise, mean local sweat rate (forearm and upper-back) was greater post- (1.24 ± 0.20 mg cm-2  min-1 ) compared to pre- (1.04 ± 0.25 mg cm-2  min-1 , P < 0.01) training, but similar between UF (0.94 ± 0.31 mg cm-2  min-1 , P = 0.90) and F (1.02 ± 0.30 mg cm-2  min-1 ). The ΔTre at 60 min of exercise was greater pre- (1.13 ± 0.16°C, P < 0.01) compared to post- (0.96 ± 0.14°C) training, but similar between UF (0.85 ± 0.29°C, P = 0.22) and F (0.95 ± 0.22°C). Taken together, aerobic training, not V̇O2max per se, confers an increased ωmax , greater sweat rate, and smaller rise in core temperature during uncompensable heat stress in fit individuals.

Impact of passive heat acclimation on markers of kidney function during heat stress.

NEW FINDINGS: What is the central question of this study? Does passive heat acclimation alter glomerular filtration rate and urine-concentrating ability in response to passive heat stress? What is the main finding and its importance? Glomerular filtration rate remained unchanged after passive heat stress, and heat acclimation did not alter this response. However, heat acclimation mitigated the reduction in urine-concentrating ability and reduced the incidence of albuminuria in young healthy adults after passive heat stress. Collectively, these results suggest that passive heat acclimation might improve structural integrity and reduce glomerular permeability during passive heat stress. ABSTRACT: Little is known about the effect of heat acclimation on kidney function during heat stress. The purpose of this study was to determine the impact of passive heat stress and subsequent passive heat acclimation on markers of kidney function. Twelve healthy adults (seven men and five women; 26 ± 5 years of age; 72.7 ± 8.6 kg; 172.4 ± 7.5 cm) underwent passive heat stress before and after a 7 day controlled hyperthermia heat acclimation protocol. The impact of passive heat exposure on urine and serum markers of kidney function was evaluated before and after heat acclimation. Glomerular filtration rate, determined from creatinine clearance, was unchanged with passive heat stress before (pre, 133 ± 41 ml min-1 ; post, 127 ± 51 ml min-1 ; P = 0.99) and after (pre, 129 ± 46 ml min-1 ; post, 130 ± 36 ml min-1 ; P = 0.99) heat acclimation. The urine-to-serum osmolality ratio was reduced after passive heating (P < 0.01), but heat acclimation did not alter this response. In comparison to baseline, free water clearance was greater after passive heating before (pre, -0.86 ± 0.67 ml min-1 ; post, 0.40 ± 1.01 ml min-1 ; P < 0.01) but not after (pre, -0.16 ± 0.57 ml min-1 ; post, 0.76 ± 1.2 ml min-1 ; P = 0.11) heat acclimation. Furthermore, passive heating increased the fractional excretion rate of potassium (P < 0.03) but not sodium (P = 0.13) or chloride (P = 0.20). Lastly, heat acclimation reduced the fractional incidence of albuminuria after passive heating (before, 58 ± 51%; after, 8 ± 29%; P = 0.03). Collectively, these results demonstrate that passive heat stress does not alter the glomerular filtration rate. However, heat acclimation might improve urine-concentrating ability and filtration within the glomerulus.

Integrative crosstalk between hypoxia and the cold: Old data and new opportunities.

NEW FINDINGS: What is the topic of this review? The aim was to examine the influence of hypoxia on thermoregulatory and cardiovascular control in the cold. What advances does it highlight? Exposure to hypoxia seems to alter both thermoregulatory and cardiovascular control, but these conclusions are based on limited data, and this review highlights the need for future research in this area. ABSTRACT: Cold stress and hypoxia have been the subject of research for decades; however, humans often encounter these stressors together, such as in the alpine environment. Therefore, this review summarizes previous data with respect to the influence of hypoxia on thermoregulatory and cardiovascular control in the cold and presents new ideas for the future. Altogether, little to no evidence is available on the integrative and adaptive mechanisms by which the human body regulates heat conservation, oxygen delivery and maintenance of blood pressure.

Improved neural control of body temperature following heat acclimation in humans.

KEY POINTS: With the advent of more frequent extreme heat events, adaptability to hot environments will be crucial for the survival of many species, including humans. However, the mechanisms that mediate human heat adaptation have remained elusive. We tested the hypothesis that heat acclimation improves the neural control of body temperature. Skin sympathetic nerve activity, comprising the efferent neural signal that activates heat loss thermoeffectors, was measured in healthy adults exposed to passive heat stress before and after a 7 day heat acclimation protocol. Heat acclimation reduced the activation threshold for skin sympathetic nerve activity, leading to an earlier activation of cutaneous vasodilatation and sweat production. These findings demonstrate that heat acclimation improves the neural control of body temperature in humans. ABSTRACT: Heat acclimation improves autonomic temperature regulation in humans. However, the mechanisms that mediate human heat adaptation remain poorly understood. The present study tested the hypothesis that heat acclimation improves the neural control of body temperature. Body temperatures, skin sympathetic nerve activity, cutaneous vasodilatation, and sweat production were measured in 14 healthy adults (nine men and five women, aged 27 ± 5 years) during passive heat stress performed before and after a 7 day heat acclimation protocol. Heat acclimation increased whole-body sweat rate [+0.54 L h-1 (0.32, 0.75), P < 0.01] and reduced resting core temperature [-0.29°C (-0.40, -0.18), P < 0.01]. During passive heat stress, the change in mean body temperature required to activate skin sympathetic nerve activity was reduced [-0.21°C (-0.34, -0.08), P < 0.01] following heat acclimation. The earlier activation of skin sympathetic nerve activity resulted in lower activation thresholds for cutaneous vasodilatation [-0.18°C (-0.35, -0.01), P = 0.04] and local sweat rate [-0.13°C (-0.24, -0.01), P = 0.03]. These results demonstrate that heat acclimation leads to an earlier activation of the neural efferent outflow that activates the heat loss thermoeffectors of cutaneous vasodilatation and sweating.

Cardiac function during heat stress: impact of short-term passive heat acclimation.

A lower heart rate (HR) during heat exposure is a classic marker of heat acclimation (HA), although it remains unclear whether this adaptation occurs secondary to reduced thermal strain and/or improvements in cardiac function. We evaluated the hypothesis that short-term passive HA reduces HR and improves cardiac function during passive heating. Echocardiography was performed under thermoneutral and hyperthermic conditions in 10 healthy adults (9 men/1 woman, 29 ± 6 yr old), pre and post 7 days of controlled hyperthermia. HR (P = 0.61), stroke volume (P = 0.99), and cardiac output (P = 0.99), were similar on days 1 and 7 of HA. Core (pre: 38.17 ± 0.42, post: 38.15 ± 0.27°C, P = 0.95) and mean skin (pre: 38.24 ± 0.41, post: 38.51 ± 0.29°C, P = 0.17) temperatures were similar during hyperthermic echocardiographic assessments. Cardiac systolic function was unaffected by HA (P ≥ 0.10). HA attenuated the decrease in end-diastolic volume (pre: -18 ± 18, post: -12 ± 19 mL, P = 0.05), accentuated the greater atrial contribution to diastolic filling (pre: +11 ± 5, post: +14 ± 5%, P = 0.02), and attenuated the increase in left atrial reservoir strain rate (pre: +1.5 ± 1.2, post: +0.8 ± 0.8 1/s, P = 0.02) during heating. Nonetheless, there were no differences in HR (pre: 106 ± 12, post: 104 ± 12 beats/min, P = 0.50), stroke volume (pre: 65 ± 15, post: 68 ± 13 mL, P = 0.55), or cardiac output (pre: 6.9 ± 2.0, post: 7.1 ± 1.7 L/min, P = 0.70) during passive heating. Short-term controlled hyperthermia HA results in limited adaptations of cardiac function during passive heating.NEW & NOTEWORTHY A lower heart rate during heat exposure is a classic marker of heat acclimation (HA). It remains unknown if improved cardiac function contributes to this response. A 7-day passive HA protocol did not alter cardiac systolic function during passive heating, whereas it improved some indexes of diastolic function in young adults. Nonetheless, heart rate during heating was unaffected by HA. These results suggest that passive HA induces limited adaptations in cardiac function during passive heating.

Skin blood flow measurements during heat stress: technical and analytical considerations.

During heat stress, the skin vasculature can greatly increase conductance secondary to vasodilation. The subsequent increase in skin blood flow allows for convective heat transfer from the core to the skin and between the skin surface and the surrounding environment. Measurement of skin blood flow, therefore, provides valuable information regarding heat exchange between the body and the environment. In addition, assessment of skin blood flow can be used to study vascular control mechanisms. Most often, skin blood flow is measured by venous occlusion plethysmography, Doppler ultrasound, laser-Doppler flowmetry, and, more recently, optical coherence tomography. However, important delimitations to each of these methods, which may be dependent on the research question, must be considered when responses from these approaches are interpreted. In this brief review, we discuss these methods of skin blood flow measurement and highlight potential sources of error and limitations. We also provide recommendations to guide the interpretation of skin blood flow data.

Acute heat stress reduces biomarkers of endothelial activation but not macro- or microvascular dysfunction in cervical spinal cord injury.

Cardiovascular diseases (CVD) are highly prevalent in spinal cord injury (SCI), and peripheral vascular dysfunction might be a contributing factor. Recent evidence demonstrates that exposure to heat stress can improve vascular function and reduce the risk of CVD in uninjured populations. We therefore aimed to examine the extent of vascular dysfunction in SCI and the acute effects of passive heating. Fifteen participants with cervical SCI and 15 uninjured control (CON) participants underwent ultrasound assessments of vascular function and venous blood sampling for biomarkers of endothelial activation (i.e., CD62e+) and apoptosis (i.e., CD31+/42b-) before and after a 60-min exposure to lower limb hot water immersion (40°C). In SCI, macrovascular endothelial function was reduced in the brachial artery [SCI: 4.8 (3.2)% vs. CON: 7.6 (3.4)%, P = 0.04] but not the femoral artery [SCI: 3.7 (2.6)% vs. CON: 4.0 (2.1)%, P = 0.70]. Microvascular function, via reactive hyperemia, was ~40% lower in SCI versus CON in both the femoral and brachial arteries ( P < 0.01). Circulating concentrations of CD62e+ were elevated in SCI versus CON [SCI: 152 (106) microparticles/µl vs. CON: 58 (24) microparticles/µl, P < 0.05]. In response to heating, macrovascular and microvascular function remained unchanged, whereas increases (+83%) and decreases (-93%) in antegrade and retrograde shear rates, respectively, were associated with heat-induced reductions of CD62e+ concentrations in SCI to levels similar to CON ( P = 0.05). These data highlight the potential of acute heating to provide a safe and practical strategy to improve vascular function in SCI. The chronic effects of controlled heating warrant long-term testing. NEW & NOTEWORTHY Individuals with cervical level spinal cord injury exhibit selectively lower flow-mediated dilation in the brachial but not femoral artery, whereas peak reactive hyperemia was lower in both arteries compared with uninjured controls. After 60 min of lower limb hot water immersion, femoral artery blood flow and shear patterns were acutely improved in both groups. Elevated biomarkers of endothelial activation in the spinal cord injury group decreased with heating, but these biomarkers remained unchanged in controls.

Hemostatic responses to exercise, dehydration, and simulated bleeding in heat-stressed humans.

Heat stress followed by an accompanying hemorrhagic challenge may influence hemostasis. We tested the hypothesis that hemostatic responses would be increased by passive heat stress, as well as exercise-induced heat stress, each with accompanying central hypovolemia to simulate a hemorrhagic insult. In aim 1, subjects were exposed to passive heating or normothermic time control, each followed by progressive lower-body negative pressure (LBNP) to presyncope. In aim 2 subjects exercised in hyperthermic environmental conditions, with and without accompanying dehydration, each also followed by progressive LBNP to presyncope. At baseline, pre-LBNP, and post-LBNP (<1, 30, and 60 min), hemostatic activity of venous blood was evaluated by plasma markers of hemostasis and thrombelastography. For aim 1, both hyperthermic and normothermic LBNP (H-LBNP and N-LBNP, respectively) resulted in higher levels of factor V, factor VIII, and von Willebrand factor antigen compared with the time control trial (all P < 0.05), but these responses were temperature independent. Hyperthermia increased fibrinolysis [clot lysis 30 min after the maximal amplitude reflecting clot strength (LY30)] to 5.1% post-LBNP compared with 1.5% (time control) and 2.7% in N-LBNP ( P = 0.05 for main effect). Hyperthermia also potentiated increased platelet counts post-LBNP as follows: 274 K/µl for H-LBNP, 246 K/µl for N-LBNP, and 196 K/µl for time control ( P < 0.05 for the interaction). For aim 2, hydration status associated with exercise in the heat did not affect the hemostatic activity, but fibrinolysis (LY30) was increased to 6-10% when subjects were dehydrated compared with an increase to 2-4% when hydrated ( P = 0.05 for treatment). Central hypovolemia via LBNP is a primary driver of hemostasis compared with hyperthermia and dehydration effects. However, hyperthermia does induce significant thrombocytosis and by itself causes an increase in clot lysis. Dehydration associated with exercise-induced heat stress increases clot lysis but does not affect exercise-activated or subsequent hypovolemia-activated hemostasis in hyperthermic humans. Clinical implications of these findings are that quickly restoring a hemorrhaging hypovolemic trauma patient with cold noncoagulant fluids (crystalloids) can have serious deleterious effects on the body's innate ability to form essential clots, and several factors can increase clot lysis, which should therefore be closely monitored.

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.

Volume loading augments cutaneous vasodilatation and cardiac output of heat stressed older adults.

KEY POINTS: Age-related changes in cutaneous microvascular and cardiac functions limit the extent of cutaneous vasodilatation and the increase in cardiac output that healthy older adults can achieve during passive heat stress. However, it is unclear if these age-related changes in microvascular and cardiac functions maximally restrain the levels of cutaneous vasodilatation and cardiac output that healthy older adults can achieve during heat stress. We observed that rapid volume loading, performed during passive heat stress, augments both cutaneous vasodilatation and cardiac output in healthy older humans. These findings demonstrate that the microcirculation of healthy aged skin can further dilate during passive heat exposure, despite peripheral limitations to vasodilatation. Furthermore, healthy older humans can augment cardiac output when cardiac pre-load is increased during heat stress. ABSTRACT: Primary ageing markedly attenuates cutaneous vasodilatation and the increase in cardiac output during passive heating. However, it remains unclear if these responses are maximally restrained by age-related changes in cutaneous microvascular and cardiac functions. We hypothesized that rapid volume loading performed during heat stress would increase cardiac output in older adults without parallel increases in cutaneous vasodilatation. Twelve young (Y: 26 ± 5 years) and ten older (O: 69 ± 3 years) healthy adults were passively heated until core temperature increased by 1.5°C. Cardiac output (thermodilution), forearm vascular conductance (FVC, venous occlusion plethysmography) and cutaneous vascular conductance (CVC, laser-Doppler) were measured before and after rapid infusion of warmed saline (15 mL kg-1 , ∼7 min). While heat stressed, but prior to saline infusion, cardiac output (O: 6.8 ± 0.4 vs. Y: 9.4 ± 0.6 L min-1 ), FVC (O: 0.08 ± 0.01 vs. Y: 0.17 ± 0.02 mL (100 mL min-1  mmHg-1 )-1 ), and CVC (O: 1.29 ± 0.34 vs. Y: 1.93 ± 0.30 units mmHg-1 ) were lower in older adults (all P < 0.01). Rapid saline infusion increased cardiac output (O: +1.9 ± 0.3, Y: +1.8 ± 0.7 L min-1 ), FVC (O: +0.015 ± 0.007, Y: +0.048 ± 0.013 mL (100 mL min-1  mmHg-1 )-1 ), and CVC (O: +0.28 ± 0.10, Y: +0.29 ± 0.16 units mmHg-1 ) in both groups (all P < 0.01). The absolute increase in cardiac output and CVC were similar between groups, whereas FVC increased to a greater extent in young adults (P < 0.01). These results demonstrate that healthy older adults can achieve greater levels of cutaneous vasodilatation and cardiac output during passive heating.

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.