Search

Acute exposure to terrestrial altitude (hypobaric hypoxia) causes decrements in endurance performance relative to sea level. Altitude acclimatization consistently results in partial attenuation of these decrements, but due to logistical challenges, it is not readily implemented. We discuss mechanisms and impact (or lack thereof) of other non-acclimatization interventions to improve endurance performance and provide suggestions for future research directions., (Copyright © 2025 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Purpose: To evaluate the significance of body surface area-to-mass ratio (BSA/mass) on the heat-tolerance test (HTT) results. We hypothesized that individuals defined as heat tolerant (HT) would have on average higher BSA/mass compared with heat intolerant (HI) individuals., Methods: A retrospective reanalysis of the HTT results of 517 soldiers (age, 18-38 yr; M/F, 96%:4%), who were tested by the Israel Defense Forces HTT protocol. The criterion for heat tolerance in the current analysis was a rectal temperature (T re ) plateau during the second hour of the test. A logistic regression analysis to evaluate the predictive power of BSA/mass for heat intolerance was performed; the spline model was applied to show the odds for heat intolerance across BSA/mass., Results: In men BSA/mass of HI individuals was lower than HT individuals (248 ± 19 vs 262 ± 18 cm 2 ·kg -1 , P < 0.01, d = 0.76). In women a similar trend was noted but with no statistical significance between HT and HI groups. The odd ratio for heat intolerance for every unit increase in BSA/mass was 0.97 (95% confidence interval, 0.95-0.99). The spline model plateaued above BSA/mass of 270 cm 2 ·kg -1 ., Conclusions: The results imply that body-core temperature responses to a standard exercise-heat stress (fixed external work rate and climatic conditions) are influenced by BSA/mass. More specifically, lack of a steady state in T re (indicating heat intolerance) was more likely to occur with every unit decrease in BSA/mass. These findings contribute to a better understanding of the role of body anthropometry in the response to a standard exercise-heat task that might have an implication on clinical decision making about return to duty/play of soldiers, athletes, and others who deemed to be identified as HI., (Copyright © 2024 by the American College of Sports Medicine.)

Understanding physiological mechanisms of tolerance to heat exposure, and potential ways to improve such tolerance, is increasingly important in the context of ongoing climate change. We discuss the concept of heat tolerance in humans and experimental models (primarily rodents), including intracellular mechanisms and improvements in tolerance with heat acclimation.

Rising global temperatures, driven by climate change, pose a threat to human health and regional livability. Empirical data and biophysical model-derived estimates suggest that the critical environmental limits (CELs) for livability are dependent on ambient temperature and humidity. We use a well-validated, physiology-based, six-cylinder thermoregulatory model (SCTM) to independently derive CELs during sustained minimal, light, and moderate activity across a broad range of ambient temperatures and humidity levels and compare with published data. The activity and environments were considered livable if predicted core temperatures did not reach 38 ± 0.25°C within 6 h. The outcomes for minimal activity revealed CELs ranging from 34°C/95% relative humidity (RH) to 50°C/5% RH. Corresponding dry heat losses ranged from 14 to -72 W·m -2 (negative = heat gain) and evaporative heat losses ranged from 39 to 104 W·m -2 . The wet-bulb temperature ( T wb ) at the CELs ranged from 33.3°C to 20.9°C. Activity shifted CELs toward lower temperatures and humidities. Importantly, our predicted CELs largely agree with observed livability CELs from physiology and those from a biophysical model. The physiology-grounded SCTM has utility for assessing the impact of climate change on regional livability. NEW & NOTEWORTHY This study is the first to use a physiology-grounded thermoregulatory model to predict critical environmental limits (CELs) above which human thermoregulatory capacity is exceeded. The model outcomes closely approximate empirically derived CELs, showing it is a strong model for estimating and preparing for the impact of climate warming on local, regional, and world human population livability and migration.

Women are participating in military and athletic activities in the heat in increasing numbers, but potential sex differences in sequelae from exertional heat illness remain poorly understood. We tested the hypothesis that women suffering from exertional heat stroke (EHS) would have similar severity of organ damage biomarkers compared with men, as measured in a hospital setting. We studied women and men presenting with EHS to the emergency department at Fort Moore, GA. We measured creatinine (CR), creatine kinase (CK), alanine-transaminase (ALT), aspartate aminotransferase (AST), and estimated glomerular filtration rate (eGFR). Core temperature was also assessed by medical personnel. Biomarker data were obtained for 62 EHS cases (11 women). Men were significantly taller, and heavier, and had larger body mass index (BMI) and body surface area ( P < 0.05 for all). The highest recorded body core temperature was not different between groups [women: 41.11°C (40.06, 41.67); men: 41.11°C (40.28, 41.72), P = 0.57]. Women had significantly lower peak CR [women: 1.39 (1.2, 1.48) m·dL -1 ; men: 1.75 (1.53, 2.16) mg·dL -1 , P < 0.01] and peak CK [women: 584 (268, 2,412) U·L -1 ; men: 2,183 (724, 5,856) U·L -1 , P = 0.02]. Peak ALT and AST were not different between groups; during recovery time points, ALT and AST were either similar or lower in women. Women spent approximately half as much time in the hospital following admittance compared with men. Our findings suggest that women may be less susceptible to organ injury resulting from EHS. Further research is necessary to understand the pathophysiology underlying these differences and how biomarkers of end-organ damage severity can differ between women and men following EHS. NEW & NOTEWORTHY We studied otherwise healthy women and men after exertional heat stroke in a military training environment. Peak values for biomarkers of kidney and muscle damage were lower in women compared with men despite similar (highest recorded) body core temperatures. During recovery, organ damage markers were similar or lower in women. These sex differences may indicate differences in the pathophysiology of responses, but more work is needed to clarify specific mechanisms.

Exertional heat stroke (EHS) is a medical emergency characterized by elevated body temperature and central nervous system dysfunction, and it can include dizziness, confusion and loss of consciousness, as well as long-term organ and tissue damage. EHS is distinct from classic, or passive, heat stroke and is most commonly observed during intense physical activity in warfighters, athletes, and laborers. EHS is an ongoing non-combat threat that represents a risk to both the health and readiness of military personnel. Potential risk factors and their mitigation have been the subject of investigation for decades. One risk factor that is often mentioned in the literature, but not well quantified, is that of individual motivation to excel, wherein highly trained military personnel and athletes exert themselves beyond their physiological limits because of a desire to complete tasks and goals. The motivation to excel in tasks with high standards of achievement, such as those within elite military schools, appears to create an environment in which a disproportionately high number of exertional heat illness casualties occur. Here, we review existing biomedical literature to provide information about EHS in the context of motivation as a risk factor and then discuss five cases of EHS treated at Martin Army Community Hospital at Fort Moore, GA, from 2020 to 2022. In our discussion of the cases, we explore the influence of motivation on each occurrence. The findings from this case series provide further evidence of motivation to excel as a risk factor for EHS and highlight the need for creative strategies to mitigate this risk., (2024.)

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., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

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.

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.

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.

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.

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 Tcore critical value 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., (© 2023 Institute of Physics and Engineering in Medicine.)

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.

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 V̇o 2max . 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.

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., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

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., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

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/m 2 (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.

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 (T c ), heart rate (HR), and whole body sweating rate (SR) were compared across 1d, 5d, and 8d of HA. Criteria for HA were delta (Δ)T c  ≤ 0.9 °C and ΔHR≤33 beats·min -1 ., Results: Group averages on 1d, 5d, and 8d of HA for end exercise T c (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. ΔT c (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 T c and HR, ∼1/3 achieve STHA. Future research should evaluate potential mechanisms, and whether similar inter-individual variability occurs in women., (Published by Elsevier Ltd.)

Military and/or emergency services personnel may be required to perform high-intensity physical activity during exposure to elevated inspired carbon dioxide (CO 2 ). Although many of the physiological consequences of hypercapnia are well characterized, the effects of graded increases in inspired CO 2 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 CO 2 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% CO 2 . 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% CO 2 trial due to lightheadedness during the run. Compared with the 0% CO 2 trial, run performance was 5 ± 3% and 7 ± 3% slower in the 2% and 4% CO 2 trials, respectively (both P < 0.001). Run performance was significantly slower with 4% versus 2% CO 2 ( 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% CO 2 trial compared with both the 0% and 2% trials. Overall, our findings show that graded increases in inspired CO 2 impair endurance performance in a stepwise manner in healthy humans.

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., (© 2022 The Authors. Experimental Physiology © 2022 The Physiological Society.)

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., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The foramen ovale is an essential component of the fetal circulation contributing to oxygenation and carbon dioxide elimination that remains patent under certain circumstances in ∼30% of the healthy adult population, without major negative sequelae in most. Adults with a patent foramen ovale (PFO) have a greater tendency to develop symptoms of acute mountain sickness and high-altitude pulmonary oedema upon ascent to high altitude, and PFO presence is associated with worse cardiopulmonary function in chronic mountain sickness. This increase in altitude illness prevalence may be related to dysregulated cerebral blood flow associated with altered respiratory chemoreflex sensitivity; however, the mechanisms remain to be elucidated. Interestingly, men with a PFO appear to have a shift in thermoregulatory control to higher internal temperatures, both at rest and during exercise, and they have blunted thermal hyperpnoea. The teleological 'reason' for this thermoregulatory shift is unclear, but the shift of ∼0.5°C in core body temperature does not appear to be sufficient to have any significant negative consequences in terms of risk of heat illness. Further work in this area is needed, particularly in women, to evaluate mechanisms of heat storage and dissipation in these individuals compared to people without a PFO. Consequences of a PFO in SCUBA divers include a greater incidence of unprovoked decompression sickness, but whether PFO is beneficial or detrimental to breath hold diving remains unexplored. Whether PFO presence will explain interindividual variability in responses to, and consequences from, other environmental stressors such as spaceflight remain entirely unknown., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

Abstract: Since 1948, the United States military has been open to both men and women as permanent party service members. However, in the majority of the time since, there have been a subset of military occupational specialties (MOS), or job descriptions, open only to men. In particular, jobs requiring more intense physical and/or environmental strain were considered to be beyond the physiological capabilities of women. In the present analysis, we review the literature regarding neuromuscular, physical performance, and environmental physiology in women, to highlight that women have no inherent limitation in their capacity to participate in relevant roles and jobs within the military, within accepted guidelines to promote risk mitigation across sexes. First, we discuss performance and injury risk: both neuromuscular function and physical capabilities. Second, physiological responses to environmental stress. Third, we discuss risk as it relates to reproductive health and nutritional considerations. We conclude with a summary of current physiological, performance, and injury risk data in men and women that support our overarching purpose, as well as suggestions for future directions., (Copyright © 2021 by the American College of Sports Medicine.)

There are clear differences between men and women, and differences among races, in the incidence and prevalence of hypertension. Furthermore, there is extensive inter-individual variability among humans in the extent to which sodium ingestion alters blood pressure. Orthostatic intolerance and orthostatic hypotension are more common in women; these are often treated with a high salt diet, which has variable efficacy in increasing blood volume and blood pressure. Conversely, people with certain forms of hypertension are often counseled to decrease their sodium intake. Non-Hispanic Black men and women have higher rates of hypertension compared to non-Hispanic White men and women and other racial/ethnic groups. In aggregate, Black women appear to have better orthostatic tolerance than White women. In the present paper, we summarize and evaluate the current evidence for mechanisms of blood pressure regulation in men and women, as well as differences between Black and White groups, with a focus on cardiovascular responses to salt and differences among these groups. We also provide a brief review of factors that are not traditionally considered to be "biological" - such as socio-economic disparities resulting from historic and contemporary inequity across racial groups. These non-biological factors have direct and substantial influences on cardiovascular mechanisms, as well as implications for the influences of salt and sodium intake on blood pressure and cardiovascular health. We conclude that both biological and socio-economic factors provide critical modulating influences when considering the impacts of sodium on cardiovascular health as functions of race and sex., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The purpose of this study was to investigate the relationship between volume regulatory biomarkers and the estrogen to progesterone ratio (E:P) prior to and following varying methods and degrees of dehydration. Ten women (20 ± 1 year, 56.98 ± 7.25 kg, 164 ± 6 cm, 39.59 ± 2.96 mL•kg•min -1 ) completed four intermittent exercise trials (1.5 h, 33.8 ± 1.3°C, 49.5 ± 4.3% relative humidity). Testing took place in two hydration conditions, dehydrated via 24-h fluid restriction (Dehy, USG > 1.020) and euhydrated (Euhy, USG ≤ 1.020), and in two phases of the menstrual cycle, the late follicular phase (days 10-13) and midluteal phase (days 18-22). Change in body mass (%BMΔ), serum copeptin concentration, and plasma osmolality (P osm ) were assessed before and after both dehydration stimuli (24-h fluid restriction and exercise heat stress). Serum estrogen and progesterone were analyzed pre-exercise only. Estrogen concentration did not differ between phases or hydration conditions. Progesterone was significantly elevated in luteal compared to follicular in both hydration conditions (Dehy-follicular: 1.156 ± 0.31, luteal: 5.190 ± 1.56 ng•mL -1 , P < 0.05; Euhy-follicular: 0.915 ± 0.18, luteal: 4.498 ± 1.38 ng·mL -1 , P < 0.05). As expected, E:P was significantly greater in the follicular phase compared to luteal in both hydration conditions (Dehy-F:138.94 ± 89.59, L: 64.22 ± 84.55, P < 0.01; Euhy-F:158.13 ± 70.15, L: 50.98 ± 39.69, P < 0.01, [all •10 3 ]). Copeptin concentration was increased following 24-h fluid restriction and exercise heat stress (mean change: 18 ± 9.4, P < 0.01). We observed a possible relationship of lower E:P and higher copeptin concentration following 24-h fluid restriction ( r = -0.35, P = 0.054). While these results did not reach the level of statistical significance, these data suggest that the differing E:P ratio may alter fluid volume regulation during low levels of dehydration but have no apparent impact after dehydrating exercise in the heat., Competing Interests: SK has provided scientific consultation to Danone Research and Quest Diagnostics and has active research grants with Danone Research and Standard Process. DC has served as expert witness and received consulting honoraria from Clif Bar, Sports Innovation Laboratories, and the National Football League, funding from Gatorade, and royalties from Jones and Bartlett, Springer, LWW, Wolters-Kluwer Publishers, Up-to-Date, and Routledge/Taylor & Francis Group. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Giersch, Charkoudian, Morrissey, Butler, Colburn, Caldwell, Kavouras and Casa.)

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., Competing Interests: No potential conflict of interest was reported by the authors., (This work was authored as part of the Contributor’s official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.)

Although it is well established that dehydration has a negative impact on thermoregulation during exercise in the heat, it is unclear whether this effect of dehydration is different between men and women, or across the phases of the menstrual cycle (MC). Twelve men and seven women (men: 20 ± 2 years, 70.13 ± 10.5 kg, 173.4 ± 6.0 cm, 54.2 ± 8.6 ml kg -1  min -1 ; women: 20 ± 2 years, 57.21 ± 7.58 kg, 161 ± 5 cm, 40.39 ± 3.26 ml kg -1  min -1 ) completed trials either euhydrated (urine specific gravity, USG ≤ 1.020, Euhy) or dehydrated (USG > 1.020, Dehy). Trial order was randomized and counterbalanced; men completed two trials (MEuhy and MDehy) and women completed four over two MC phases (late follicular: days 10-13, FDehy, FEuhy; midluteal: days 18-22, LDehy, LEuhy). Each trial consisted of 1.5 h, split into two 30 min blocks of exercise (B1 and B2, 15 min at 11 W/kg & 15 min at 7 W/kg) separated by 15 min rest in between and after. Rectal temperature (T re ) was measured continuously and estimated sweat loss was calculated from the body mass measured before and after each block of exercise. When dehydrated, the rate of rise in T re was greater in women in the first block of exercise compared to men, independently of the MC phase (MDehy: 0.03 ± 0.03°C/min, FDehy: 0.06 ± 0.02, LDehy: 0.06 ± 0.02, p = 0.03). Estimated sweat loss was lower in all groups in B1 compared to B2 when dehydrated (p < 0.05), with no difference between sexes for either hydration condition. These data suggest that women may be more sensitive to the negative thermoregulatory effects of dehydration during the early stages of exercise in the heat., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Athletes and certain occupations (e.g., military, firefighters) must navigate unique heat challenges as they perform physical tasks during prolonged heat stress, at times while wearing protective clothing that hinders heat dissipation. Such environments and activities elicit physiological adjustments that prioritize thermoregulatory skin perfusion at the expense of arterial blood pressure and may result in decreases in cerebral blood flow. High levels of skin blood flow combined with an upright body position augment venous pooling and transcapillary fluid shifts in the lower extremities. Combined with sweat-driven reductions in plasma volume, these cardiovascular alterations result in levels of cardiac output that do not meet requirements for brain blood flow, which can lead to orthostatic intolerance and occasionally syncope. Skin surface cooling countermeasures appear to be a promising means of improving orthostatic tolerance via autonomic mechanisms. Increases in transduction of sympathetic activity into vascular resistance, and an increased baroreflex set-point have been shown to be induced by surface cooling implemented after passive heating and other arterial pressure challenges. Considering the further contribution of exercise thermogenesis to orthostatic intolerance risk, our goal in this review is to provide an overview of post-exercise cooling strategies as they are capable of improving autonomic control of the circulation to optimize orthostatic tolerance. We aim to synthesize both basic and applied physiology knowledge available regarding real-world application of cooling strategies to reduce the likelihood of experiencing symptomatic orthostatic intolerance after exercise in the heat., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Seeley, Giersch and Charkoudian.)

Purpose: This study aimed to characterize HTT specificity and to determine any effect of HA on the outcome., Methods: Thirteen unacclimatized, healthy men (V˙O2peak, 43.0 ± 4.8 mL·kg-1⋅min-1) with no previous history of heat illness completed 8 d of HA using the HTT protocol (40°C/40% RH; 120 min; 5 km·h-1 and 2% grade). Heart rate (HR) and core temperature (Tcore) recorded every 5 min during exercise and at the end of 120 min (terminal value) were compared between days 1 and 8. Test specificity (given no previous history of heat illness, the probability of being heat tolerant) was calculated on days 1 and 8., Results: There was a significant reduction in HR and Tcore between days 1 and 8, indicating successful HA. All volunteers successfully completed 120 min of walking on all days. HTT specificity ranged between 54% and 85% on day 1 and between 77% and 92% on day 8, depending on the HTT criteria used., Conclusion: Young healthy men without any previous heat illness experienced a 15% to 46% false-positive fail rate for the HTT without HA. After HA, the false-positive fail rate decreased to between 8% and 13%. Outcomes of the HTT are significantly affected by the criteria used and by HA status. The use of HTT for RTA decisions should be done with the recognition of these effects., (Copyright © 2020 by the American College of Sports Medicine.)

Toussaint, Claudia M., Robert W. Kenefick, Frank A. Petrassi, Stephen R. Muza, and Nisha Charkoudian. Altitude, acute mountain sickness, and acetazolamide: recommendations for rapid ascent. High Alt Med Biol . 22:5-13, 2021. Background: Sea level natives ascending rapidly to altitudes above 1,500 m often develop acute mountain sickness (AMS), including nausea, headaches, fatigue, and lightheadedness. Acetazolamide (AZ), a carbonic anhydrase inhibitor, is a commonly used medication for the prevention and treatment of AMS. However, there is continued debate about appropriate dosing, particularly when considering rapid and physically demanding ascents to elevations above 3,500 m by emergency medical and military personnel. Aims: Our goal in the present analysis was to evaluate and synthesize the current literature regarding the use of AZ to determine the most effective dosing for prophylaxis and treatment of AMS for rapid ascents to elevations >3,500 m. These circumstances are specifically relevant to military and emergency medical personnel who often need to ascend rapidly and perform physically demanding tasks upon arrival at altitude. Methods: We conducted a literature search from April 2018 to February 2020 using PubMed, Google Scholar, and Web of Science to identify randomized controlled trials that compared AZ with placebo or other treatment with the primary endpoint of AMS incidence and severity. We included only research articles/studies that focused on evaluation of AZ use during rapid ascent. Results: Four doses of AZ (125, 250, 500, and 750 mg daily) were identified as efficacious in decreasing the incidence and/or severity of AMS during rapid ascents, with evidence of enhanced effectiveness with higher doses. Conclusions: For military, emergency medical, or other activities involving rapid ascent to altitudes >3,500 m, doses 500-750 mg/day within 24 hours of altitude exposure appear to be the most effective for minimizing symptoms of AMS.

Over the past several decades, it has become increasingly clear that women have distinct cardiovascular profiles compared to men. In this review, our goal is to provide an overview of the literature regarding the influences of female sex and reproductive hormones (primarily estradiol) on mechanisms of cardiovascular control relevant to regulation of blood pressure, body temperature, and cerebral blood flow. Young women tend to have lower resting blood pressure compared with men. This sex difference is reversed at menopause, when women develop higher sympathetic nerve activity and the risk of systemic hypertension increases sharply as postmenopausal women age. Vascular responses to thermal stress, including cutaneous vasodilation and vasoconstriction, are also affected by reproductive hormones in women, where estradiol appears to promote vasodilation and heat dissipation. The influence of reproductive hormones on cerebral blood flow and sex differences in the ability of the cerebral vasculature to increase its blood flow (cerebrovascular reactivity) are relatively new areas of investigation. Sex and hormonal influences on integrative blood flow regulation have further implications during challenges to physiological homeostasis, including exercise. We propose that increasing awareness of these sex-specific mechanisms is important for optimizing health care and promotion of wellness in women across the life span., (© 2020 Federation of American Societies for Experimental Biology.)

Reproductive hormones have significant nonreproductive physiological effects, including altering fluid regulation. Our purpose was to explore the impact of sex and menstrual cycle (MC) phase on volume-regulatory responses to 24-h fluid restriction (24-h FR). Participants (men: n = 12, 20 ± 2 yr; women: n = 10, 20 ± 1 yr) were assigned two randomized and counterbalanced fluid prescriptions [Euhy: euhydrated, urine specific gravity (USG) < 1.020; Dehy: 24-h FR, USG > 1.020]. Men completed both (MEuhy, MDehy), while women completed both in the late-follicular ( days 10-13 ; FDehy, FEuhy) and midluteal ( days 18-22 ; LDehy, LEuhy) phases. We measured body mass, plasma and urine osmolality (P osm , U osm ), urine specific gravity (USG), urine color (U col ), and serum copeptin; 24-h FR yielded mild dehydration without influence of sex or MC ( P > 0.05). Copeptin increased in men following Dehy (pre: 8.2 ± 5.2, post: 15.8 ± 12.6, P = 0.04) but not in women (FDehy pre: 4.3 ± 1.6, post: 10.5 ± 6.9, P = 0.06; LDehy pre: 5.6 ± 3.5, post: 10.4 ± 6.2, P = 0.16). In FDehy, P osm increased following FR (pre: 288 ± 2, post: 292 ± 1, P = 0.03) but not in men (pre: 292 ± 3, post: 293 ± 2, P = 0.46). No MC differences were observed between body mass loss, P osm , U osm , USG, and copeptin ( P > 0.05). These results suggest that volume-regulatory responses to 24-h FR were present in men but not in women, without apparent effects of the menstrual cycle.