Regulation of body temperature and blood pressure in women: Mechanisms and implications for heat illness risk.

Increasing global temperatures due to ongoing climate change phenomena have resulted in increased risk of exertional heat illness in otherwise healthy, young individuals who work or play in the heat. With increasing participation of women in athletic, military and industrial activities that involve exertion in the heat, there is a growing need to study female physiology in this context. Mechanisms controlling blood pressure and body temperature have substantial overlap in humans, largely due to autonomic mechanisms which contribute to both. Similarly, illnesses that result from excessive heat exposure can often be traced back to imbalances in one or more of these autonomic mechanisms. In recent years, there has been increased recognition of the importance of sex as a biological variable for basic and applied research in these areas. The goal of this paper is to present an update on the integrative physiology and pathophysiology of responses to heat stress in women (thermoregulation and blood pressure regulation). In this context, it is often the case that differences between sexes are presented as 'advantages' and 'disadvantages' of one sex over the other. In our opinion, this is an over-simplification of the physiology which ignores the nuances and complexities of the integrative physiology of responses to heat exposure and exercise, and their relevance for practical outcomes.

Modeling thermoregulatory responses during high-intensity exercise in warm environments.

The six cylinder thermoregulatory model (SCTM) has been validated thoroughly for resting humans. This type of modeling is helpful to predict and develop guidance for safe performance of work and recreational activities. In the context of a warming global climate, updating the accuracy of the model for intense exercise in warm environments will help a wide range of individuals in athletic, recreational, and military settings. Three sets of previously collected data were used to determine SCTM accuracy. Dataset 1: two groups [large (LG) 91.5 kg and small (SM) 67.7 kg] of individuals performed 60 min of semirecumbent cycling in temperate conditions (25.1°C) at metabolic rates of 570-700 W. Dataset 2: two LG (100 kg) and SM (65.8 kg) groups performed 60 min of semirecumbent cycling in warm/hot environmental conditions (36.2°C) at metabolic rates of 590-680 W. Dataset 3: seven volunteers completed 8-km track trials (∼30 min) in cool (17°C) and warm (30°C) environments. The volunteers' metabolic rates were estimated to be 1,268 W and 1,166 W, respectively. For all datasets, SCTM-predicted core temperatures were found to be similar to the observed core temperatures. The root mean square deviations (RMSDs) ranged from 0.06 to 0.46°C with an average of 0.2°C deviation, which is less than the acceptance threshold of 0.5°C. Thus, the present validation shows that SCTM predicts core temperatures with acceptable accuracy during intense exercise in warm environments and successfully captures core temperature differences between large and small individuals.NEW & NOTEWORTHY The SCTM has been validated thoroughly for resting humans in warm and cold environments and during water immersion. The present study further demonstrated that SCTM predicts core temperatures with acceptable accuracy during intense exercise up to 1,300 W in temperate and warm environments and captures core temperature differences between large and small individuals. SCTM is potentially useful to develop guidance for safe operation in athletic, military, and occupational settings during exposure to warm or hot environments.

Relation of body surface area-to-mass ratio to risk of exertional heat stroke in healthy men and women.

Risk of exertional heat stroke (EHS) is an ongoing challenge for United States military personnel, for athletes and for individuals with occupational stressors that involve prolonged activity in hot environments. Higher body mass index (BMI) is significantly associated with increased risk for EHS in activity duty U.S. Soldiers. During exercise, heat is generated primarily by contracting skeletal muscle (and other metabolically active body mass) and dissipated based on body surface area (BSA). Thus, in compensable environments, a higher BSA·mass-1 may be a benefit to heat dissipation and decrease the risk of EHS. The purpose of the present analysis was to test the hypothesis that BSA·mass-1 ratio is an important biophysical characteristic contributing to the risk of EHS. We employed a matched case-control approach, where each individual with a diagnosis of EHS was matched to five controls who were never diagnosed with EHS but were in the same unit and had the same job title. We used a multivariate conditional logistic regression model including variables of BSA·mass-1, sex, age, military rank, and race. BSA·mass-1 significantly predicted EHS risk (P = 0.006), such that people with higher BSA·mass-1 were at lower risk of developing EHS when controlling for other potential factors such as age and race. This relationship persisted after adjustment for other anthropometric measures of body size including weight, BMI, and BSA. These data suggest that biophysical factors play an important role in EHS risk, particularly in a healthy military-aged cohort of men and women.NEW & NOTEWORTHY With the impacts of climate change yielding higher average ambient temperatures over time, the incidence of EHS for individuals participating in outdoor activities may consequently increase. With the larger sample size in this study compared with prior research in this field, we were able to use various methods that had not been applied before. For example, we were able to mutually adjust for different measurements of body size to understand which metric had the highest association with EHS risk. Understanding factors that may be modifiable may be important for developing interventions to counteract the increased risk of EHS associated with climate change.

Guidelines on the use of sex and gender in cardiovascular research.

In cardiovascular research, sex and gender have not typically been considered in research design and reporting until recently. This has resulted in clinical research findings from which not only all women, but also gender-diverse individuals have been excluded. The resulting dearth of data has led to a lack of sex- and gender-specific clinical guidelines and raises serious questions about evidence-based care. Basic research has also excluded considerations of sex. Including sex and/or gender as research variables not only has the potential to improve the health of society overall now, but it also provides a foundation of knowledge on which to build future advances. The goal of this guidelines article is to provide advice on best practices to include sex and gender considerations in study design, as well as data collection, analysis, and interpretation to optimally establish rigor and reproducibility needed to inform clinical decision-making and improve outcomes. In cardiovascular physiology, incorporating sex and gender is a necessary component when optimally designing and executing research plans. The guidelines serve as the first guidance on how to include sex and gender in cardiovascular research. We provide here a beginning path toward achieving this goal and improve the ability of the research community to interpret results through a sex and gender lens to enable comparison across studies and laboratories, resulting in better health for all.

Individualized monitoring of heat illness risk: novel adaptive physiological strain index to assess exercise-heat strain from athletes to fully encapsulated workers.

Objective. Exercise-heat strain estimation approaches often involve combinations of body core temperature (Tcore), skin temperature (Tsk) and heart rate (HR). A successful existing measure is the 'Physiological Strain Index' (PSI), which combines HR and Tcore values to estimate strain. However, depending on variables such as aerobic fitness and clothing, the equation's 'maximal/critical' Tcore must be changed to accurately represent the strain, in part because high Tsk (small Tcore-Tsk) can increase cardiovascular strain and thereby negatively affect performance. Here, an 'adaptive PSI' (aPSI) is presented where the original PSI Tcorecriticalvalue is 'adapted' dynamically by the delta between Tcore and Tsk.Approach. PSI and aPSI were computed for athletes (ELITE,N= 11 male and 8 female, 8 km time-trial) and soldiers in fully encapsulating personal protective equipment (PPE,N= 8 male, 2 km approach-march). While these were dissimilar events, it was anticipated given that the clothing and work rates would elicit similar very-high exercise-heat strain values.Main results. Mean end HR values were similar (∼180 beats min-1) with higher Tcore = 40.1 ± 0.4 °C for ELITE versus PPE 38.4 ± 0.6 °C (P< 0.05). PSI end values were different between groups (P< 0.01) and appeared 'too-high' for ELITE (11.4 ± 0.8) and 'too-low' for PPE (7.6 ± 2.0). However, aPSI values were not different (9.9 ± 1.4 versus 9.0 ± 2.5 versus;p> 0.05) indicating a 'very high' level of exercise-heat strain for both conditions.Significance. A simple adaptation of the PSI equation, which accounts for differences in Tcore-to-Tsk gradients, provides a physiological approach to dynamically adapt PSI to provide a more accurate index of exercise-heat strain under very different working conditions.

Aging in females is associated with changes in respiratory modulation of sympathetic nerve activity and blood pressure.

Sympathetic nerve activity (SNA) is tightly coupled with the respiratory cycle. In healthy human males, respiratory modulation of SNA does not change with age. However, it is unclear how this modulation is affected by age in females. We investigated whether respiratory sympathetic modulation is altered in healthy postmenopausal (PMF) versus premenopausal female (YF), and younger male (YM) adults, and determined its relationship to resting blood pressure. Muscle SNA (MSNA; microneurography), respiration (transducer belt), ECG, and continuous blood pressure were measured in 12 YF, 13 PMF, and 12 YM healthy volunteers. Respiratory modulation of MSNA was quantified during two phases of the respiratory cycle: mid-late expiration and inspiration/postinspiration. All groups showed respiratory modulation of MSNA (P < 0.0005). There was an interaction between the respiratory phase and group for MSNA [bursts/100 heartbeats (HB) (P = 0.004) and bursts/min (P = 0.029)], with smaller reductions in MSNA during inspiration observed in PMF versus the other groups. Respiratory modulation of blood pressure was also reduced in PMF versus YF (6 [2] vs. 12 [9] mmHg, P = 0.008) and YM (13 [13] mmHg, P = 0.001, median [interquartile range]). The magnitude of respiratory sympathetic modulation was related to resting blood pressure in PMF only, such that individuals with less modulation had greater resting blood pressure. The data indicate that aging in postmenopausal females is associated with less inspiratory inhibition of MSNA. This correlated with a higher resting blood pressure in PMF only. Thus, the reduced modulation of MSNA could contribute to the age-related rise in blood pressure that occurs in females.NEW & NOTEWORTHY The current study demonstrates that respiratory modulation of sympathetic nerve activity (SNA) is reduced in healthy postmenopausal (PMF) versus premenopausal females (YF). Furthermore, respiratory sympathetic modulation was negatively related to resting blood pressure in postmenopausal females, such that blood pressure was greater in individual with less modulation. Reduced respiratory sympathetic modulation may have implications for the autonomic control of blood pressure in aging postmenopausal females, by contributing to age-related sympathetic activation and reducing acute, respiratory-linked blood pressure variation.

Beating the heat: military training and operations in the era of global warming.

Global climate change has resulted in an increase in the number and intensity of environmental heat waves, both in areas traditionally associated with hot temperatures and in areas where heat waves did not previously occur. For military communities around the world, these changes pose progressively increasing risks of heat-related illnesses and interference with training sessions. This is a significant and persistent "noncombat threat" to both training and operational activities of military personnel. In addition to these important health and safety concerns, there are broader implications in terms of the ability of worldwide security forces to effectively do their job (particularly in areas that historically already have high ambient temperatures). In the present review, we attempt to quantify the impact of climate change on various aspects of military training and performance. We also summarize ongoing research efforts designed to minimize and/or prevent heat injuries and illness. In terms of future approaches, we propose the need to "think outside the box" for a more effective training/schedule paradigm. One approach may be to investigate potential impacts of a reversal of sleep-wake cycles during basic training during the hot months of the year, to minimize the usual increase in heat-related injuries, and to enhance the capacity for physical training and combat performance. Regardless of which approaches are taken, a central feature of successful present and future interventions will be that they are rigorously tested using integrative physiological approaches.

Combining hypoxia with thermal stimuli in humans: physiological responses and potential sex differences.

Increasing prevalence of native lowlanders sojourning to high altitudes (>2,500 m) for recreational, occupational, military, and competitive reasons has generated increased interest in physiological responses to multistressor environments. Exposure to hypoxia poses recognized physiological challenges that are amplified during exercise and further complicated by environments that might include combinations of heat, cold, and high altitude. There is a sparsity of data examining integrated responses in varied combinations of environmental conditions, with even less known about potential sex differences. How this translates into performance, occupational, and health outcomes requires further investigation. Acute hypoxic exposure decreases arterial oxygen saturation, resulting in a reflex hypoxic ventilatory response and sympathoexcitation causing an increase in heart rate, myocardial contractility, and arterial blood pressure, to compensate for the decreased arterial oxygen saturation. Acute altitude exposure impairs exercise performance, for example, reduced time to exhaustion and slower time trials, largely owing to impairments in pulmonary gas exchange and peripheral delivery resulting in reduced V̇o2max. This exacerbates with increasing altitude, as does the risk of developing acute mountain sickness and more serious altitude-related illnesses, but modulation of those risks with additional stressors is unclear. This review aims to summarize and evaluate current literature regarding cardiovascular, autonomic, and thermoregulatory responses to acute hypoxia, and how these may be affected by simultaneous thermal environmental challenges. There is minimal available information regarding sex as a biological variable in integrative responses to hypoxia or multistressor environments; we highlight these areas as current knowledge gaps and the need for future research.

Human performance augmentation: the importance of integrative physiological quantification.

In recent years, there has been an explosion of new approaches (technological, methodological, pharmacological, etc.) designed to improve physical performance for athletes, the military and in other applications. The goal of the present discussion is to review and quantify several ways in which physiology can provide important insights about which tools may lead to improved performance (and may therefore be worth resource investment) and which tools are less likely to provide meaningful enhancement. To address these objectives, we review examples of technological solutions/approaches in terms of the magnitude of their potential (or actual) influences: transformational, moderate, ineffective or undetermined. As one example, if there were a technology which significantly increased arterial oxygen partial pressure by 10%, this would be relatively meaningless in healthy people resting at sea level, where it would have a minimal effect on arterial oxygen content. However, there might be specific situations where such an effect would be very helpful, including at high altitude or in some patient populations. We discuss the importance of quantitative evaluation of putative approaches to performance enhancement and highlight the important role of integrative physiologists in the development and critical appraisal of these approaches.

Body mass index, but not sex, influences exertional heat stroke risk in young healthy men and women.

Exertional heat stroke (EHS) remains a persistent threat for individuals working or playing in the heat, including athletes and military and emergency service personnel. However, influence of biological sex and/or body mass index (BMI) on the risk of EHS remain poorly understood. The purpose of this study was to retrospectively assess the influence of sex and BMI on risk of EHS in the active-duty US Army. We analyzed data from 2016 to 2021, using a matched case-control approach, where each individual with a diagnosis of EHS was matched to five controls based on calendar time, unit ID, and job category, to capture control individuals who were matched to EHS events by location, time, and activity. We used a multivariate logistic regression model mutually adjusted for sex, BMI, and age to compare 745 (n = 61 F) individuals (26 ± 7 yr) with a diagnosed EHS to 4,290 (n = 384 F) case controls (25 ± 5 yr). Group average BMI were similar: 26.6 ± 3.1 (EHS) and 26.5 ± 3.6 kg/m2 (CON). BMI was significantly (P < 0.0001) associated with higher risk of EHS with a 3% increase in risk of EHS for every unit increase in BMI. Notably, sex was not associated with any difference in risk for EHS (P = 0.54). These data suggest that young healthy people with higher BMI have significantly higher risk of EHS, but, contrary to what some have proposed, this risk was not higher in young women.

Effects of sex and ageing on the human respiratory muscle metaboreflex.

Intense inspiratory muscle work evokes a sympathetically mediated pressor reflex, termed the respiratory muscle metaboreflex, in which young females demonstrate an attenuated response relative to males. However, the effects of ageing and female sex hormones on the respiratory muscle metaboreflex are unclear. We tested the hypothesis that the pressor response to inspiratory work would be similar between older males and females, and higher relative to their younger counterparts. Healthy, normotensive young (26 ± 3 years) males (YM; n = 10) and females (YF; n = 10), as well as older (64 ± 5 years) males (OM; n = 10) and females (OF; n = 10), performed inspiratory pressure threshold loading (PTL) to task failure. Older adults had a greater mean arterial pressure (MAP) response to PTL than young (P < 0.001). YF had a lower MAP compared to YM (+10 ± 6 vs. +19 ± 15 mmHg, P = 0.026); however, there was no difference observed between OF and OM (+26 ± 11 vs. +27 ± 11 mmHg, P = 0.162). Older adults had a lower heart rate response to PTL than young (P = 0.002). There was no effect of sex between young females and males (+19 ± 9 and +27 ± 11 bpm, P = 0.186) or older females and males (+17 ± 7 and +20 ± 7 bpm, P = 0.753). We conclude the respiratory muscle metaboreflex response is heightened in older adults, and the sex effect between older males and post-menopause females is absent, suggesting an effect of circulating sex hormones. KEY POINTS: The arterial blood pressure response to the respiratory muscle metaboreflex is greater in older males and females. Compared to sex-matched young individuals, there is no sex differences in the blood pressure response between older males and post-menopause females. Our results suggest the differences between males and females in the cardiovascular response to high levels of inspiratory muscle work is abolished with reduced circulating female sex hormones.

Individual variability in achievement of short-term heat acclimation during a fixed intensity protocol.

INTRODUCTION: Heat acclimation (HA) occurs with ∼8-10d of repeated heat exposure; however, adaptations can occur earlier (<7d; termed short-term heat acclimation; STHA). PURPOSE: To test the hypothesis that some, but not all, young healthy men would achieve STHA after 5d of a standard HA protocol. METHODS: We conducted a novel, post-hoc analysis of data from 13 healthy men (21 ± 3 yrs; 173 ± 8 cm; 75.1 ± 12.2 kg) who participated in an 8d HA protocol (120 min treadmill walking: 5 km h-1, 2% grade; 40 °C, 40% relative humidity). Core temperature (Tc), heart rate (HR), and whole body sweating rate (SR) were compared across 1d, 5d, and 8d of HA. Criteria for HA were delta (Δ)Tc ≤ 0.9 °C and ΔHR≤33 beats·min-1. RESULTS: Group averages on 1d, 5d, and 8d of HA for end exercise Tc (38.1 ± 0.34; 37.9 ± 0.3; 37.8 ± 0.3 °C) and HR (134 ± 17; 122 ± 13; 121 ± 13 beats·min-1) were decreased by 5d (p < 0.05) and did not decrease further by 8d. ΔTc (1.1 ± 0.36; 0.95 ± 0.45; 0.95 ± 0.33 °C) and ΔHR (36 ± 18; 33 ± 17; 33 ± 15 beats·min-1) showed similar patterns (p > 0.05). At 5d, 31% (4/13) of the volunteers achieved HA; the remaining 9 volunteers had further adaptations between 5d and 8d. SR was not different across 1d, 5d, and 8d (860 ± 148; 908 ± 210; 873 ± 203 mL h-1 respectively; p > 0.05). CONCLUSION: Our results suggest that during a fixed-intensity HA protocol in young men, using criteria of changes in Tc and HR, ∼1/3 achieve STHA. Future research should evaluate potential mechanisms, and whether similar inter-individual variability occurs in women.

Influence of graded hypercapnia on endurance exercise performance in healthy humans.

Military and/or emergency services personnel may be required to perform high-intensity physical activity during exposure to elevated inspired carbon dioxide (CO2). Although many of the physiological consequences of hypercapnia are well characterized, the effects of graded increases in inspired CO2 on self-paced endurance performance have not been determined. The aim of this study was to compare the effects of 0%, 2%, and 4% inspired CO2 on 2-mile run performance, as well as physiological and perceptual responses during time trial exercise. Twelve physically active volunteers (peak oxygen uptake = 49 ± 5 mL·kg-1·min-1; 3 women) performed three experimental trials in a randomized, single-blind, crossover manner, breathing 21% oxygen with either 0%, 2%, or 4% CO2. During each trial, participants completed 10 min of walking at ∼40% peak oxygen uptake followed by a self-paced 2-mile treadmill time trial. One participant was unable to complete the 4% CO2 trial due to lightheadedness during the run. Compared with the 0% CO2 trial, run performance was 5 ± 3% and 7 ± 3% slower in the 2% and 4% CO2 trials, respectively (both P < 0.001). Run performance was significantly slower with 4% versus 2% CO2 (P = 0.046). The dose-dependent performance impairments were accompanied by stepwise increases in mean ventilation, despite significant reductions in running speed. Dyspnea and headache were significantly elevated during the 4% CO2 trial compared with both the 0% and 2% trials. Overall, our findings show that graded increases in inspired CO2 impair endurance performance in a stepwise manner in healthy humans.

Influences of ovarian hormones on physiological responses to cold in women.

While it is clear that the ovarian hormones estradiol and progesterone have important influences on physiological thermoregulation in women, the influences of these hormones on responses to cold exposure are not well understood. Both heat conservation and heat production must increase to offset heat losses that decrease body temperature in cold ambient conditions. Cutaneous vasoconstriction conserves heat, whereas shivering and non-shivering thermogenesis produce heat - all as part of reflex physiological responses to cold exposure. Our goal in this brief review is to highlight existing knowledge and recent advances pertaining to sex and sex hormone influences on thermoeffector responses to cold stress. Estrogens have multiple influences that contribute to heat dissipation and a lower body temperature, while the influence of progesterone appears to primarily increase body temperature. Fluctuations in estrogen and progesterone across the menstrual cycle can alter the level at which body temperature is regulated. Recent evidence suggests that female reproductive hormones can modulate the cutaneous vasoconstrictor response, and may influence metabolic mechanisms such as substrate utilization during shivering and non-shivering thermogenesis. Overall, it appears that quantitative differences in cold thermoregulation between sexes are minimal when anthropometric measures are minimized, such that women do not have a strong "advantage" or "disadvantage" in terms of overall ability to tolerate cold. Thermoregulatory physiology in women during cold exposure remains relatively understudied and many mechanisms require further elucidation.

Are there sex differences in risk for exertional heat stroke? A translational approach.

NEW FINDINGS: What is the topic of this review? Whether there are sex differences in exertional heat stroke. What advances does it highlight? This review utilizes a translational model between animal and human research to explore possible physical and physiological differences with respect to risk and treatment of exertional heat stroke. ABSTRACT: Exertional heat stroke (EHS) is a potentially fatal condition brought about by a combination of physical activity and heat stress and resulting in central nervous system dysfunction and organ damage. EHS impacts several hundred individuals each year ranging from military personnel, athletes, to occupational workers. Understanding the pathophysiology and risk factors can aid in reducing EHS across the globe. While we know there are differences between sexes in mechanisms of thermoregulation, there is currently not a clear understanding of if or how those differences impact EHS risk. The purpose of this review is to assess the current status of the literature surrounding EHS from risk factors to treatment using both animal and human models. We use a translational approach, considering both animal and human research to elucidate the possible influence of female sex hormones on temperature regulation and performance in the heat and highlight the specific areas with limited research. While more work is necessary to comprehensively understand these differences, the current research presented provides a good framework for future investigations.

The Effectiveness of a Standardized Ice-Sheet Cooling Method Following Exertional Hyperthermia.

INTRODUCTION: Exertional heat illnesses remain a major threat to military service members in the United States and around the world. Exertional heat stroke (EHS) is the most severe heat illness, characterized by core hyperthermia and central nervous system dysfunction. Per current Army regulations, iced-sheet cooling (ISC) is the recommended immediate treatment for heat casualties in the field, but concerns have been raised regarding the efficacy of this approach. Thus, the purpose of this study was to quantify the cooling rate of ISC following exertional hyperthermia. MATERIALS AND METHODS: We utilized a randomized crossover design with 2 experimental trials. In both trials, exertional hyperthermia was induced by walking (3.5 mph at 5% grade) on a treadmill in an environmental chamber (40 °C, 30% RH) for up to 3 hours or until core body temperature reached 39.2 °C. After the walking portion, individuals either received ISC (experimental trial) or cooling and rested supine in the same environmental conditions for 30 minutes with no ISC (control trial). For ISC, bed sheets soaked in ice water were applied (per Army guidance) at the neck, chest, and groin with another sheet covering the body. Sheets were rotated and resoaked every 3 minutes until core temperature decreased to <38.0 °C. RESULTS: By design, participants finished exercise with increased core temperature (38.8 ± 0.39 °C vs. 38.90 ± 0.34 °C, ISC and control trials, P = 1.00). The ISC trial provided significantly (P = .023) greater cooling rates, 0.068 °C/min 95% confidence interval [CI; 0.053, 0.086], compared to the control trial, 0.047 °C/min 95% CI [0.038, 0.056]. Additionally, the time to decrease to less than 38.0 °C was significantly (P = .018) faster in the ISC trial (median = 9.3 minutes) compared to the control trial (median = 26.6 minutes). CONCLUSION: ISC increases the cooling rate of those recovering from exertional hyperthermia. With the observed cooling rate, we can extrapolate that ISC would reduce core temperature by ∼2 °C within 30 minutes during a case of EHS. We conclude that ISC provides a safe and effective alternative for the field where cold water immersion resources may not be readily available.

Corrigendum: Estrogen to Progesterone Ratio and Fluid Regulatory Responses to Varying Degrees and Methods of Dehydration.

[This corrects the article DOI: 10.3389/fspor.2021.722305.].