Exercise-heat Stress Research Articles

CARDIAC AUTONOMIC MODULATION IN INDIVIDUALS WITH CONTROLLED AND UNCOMPLICATED HYPERTENSION DURING EXERCISE-HEAT STRESS.

Impaired cardiac autonomic modulation is implicated in the development of hypertension. Exercise improves sympathovagal balance and is often prescribed for hypertension management. Environmental conditions, however, are not considered during the development of these exercise recommendations. We examined cardiac autonomic modulation, assessed using heart rate variability (HRV), in individuals (49-77 years) with (n=20) and without (n=28) controlled, uncomplicated hypertension performing three 30-minute bouts of exercise (light, moderate, vigorous) in dry heat (40.2±0.3˚C, 17±7% relative humidity), each separated by 15-minute breaks. Regardless of intensity, short bouts of exercise-heat stress did not significantly disrupt HRV in individuals with hypertension relative to normotensives.

Impact of high intensity interval exercise with and without heat stress on cardiovascular and aerobic performance: a pilot study

BackgroundHeat stress during aerobic exercise training may offer an additional stimulus to improve cardiovascular function and performance in a cool-temperate environment. However, there is a paucity of information on the additive effects of high-intensity interval exercise (HIIE) and acute heat stress. We aimed to determine the effects of HIIE in combination with acute heat stress on cardiovascular function and exercise performance.MethodsTwelve active (peak O2 consumption [VO2peak]: 47 ± 8 ml·O2/min/kg) young adults were counterbalanced to six sessions of HIIE in hot (HIIE-H, 30 ± 1 °C, 50 ± 5% relative humidity [RH]) or temperate conditions (HIIE-T, 20 ± 2 °C, 15 ± 10% RH). Resting heart rate (HR), HR variability (HRV), central (cBP) and peripheral blood pressure (pBP), peripheral mean arterial pressure (pMAP), pulse wave velocity (PWV), VO2peak, and 5-km treadmill time-trial were measured pre- and post-training.ResultsResting HR and HRV were not significantly different between groups. However, expressed as percent change from baseline, cSBP (HIIE-T: + 0.9 ± 3.6 and HIIE-H: -6.6 ± 3.0%, p = 0.03) and pSBP (HIIE-T: -2.0 ± 4.6 and HIIE-H: -8.4 ± 4.7%, p = 0.04) were lower in the heat group. Post-training PWV was also significantly lower in the heat group (HIIE-T: + 0.4% and HIIE-H: -6.3%, p = 0.03). Time-trial performance improved with training when data from both groups were pooled, and estimated VO2peak was not significantly different between groups (HIIE-T: 0.7% and HIIE-H: 6.0%, p = 0.10, Cohen’s d = 1.4).ConclusionsThe addition of acute heat stress to HIIE elicited additive adaptations in only cardiovascular function compared to HIIE alone in active young adults in temperate conditions, thus providing evidence for its effectiveness as a strategy to amplify exercise-induced cardiovascular adaptations.

Core temperature responses in well-healed burn survivors during exercise heat stress: effect of cooling modalities

Introduction: Every year, ~150,000 patients are treated in the United States with burn-related injuries. Previously, our group has shown that ~75% of burn survivors have a maximal aerobic capacity in the lowest 20th percentile rankings, relative to sex and age-adjusted non-burned individuals. This level of impairment is strongly associated with cardiovascular-specific, as well as all cause, morbidity, and mortality. Moreover, burn injuries that require grafting impair thermoregulation, and the subsequent increases in skin and core temperature may dissuade these individuals from engaging in exercise and/or physical activity. Low-energy cooling strategies have potential to attenuate increases in core temperature in burn survivors, which may promote regular physical activity. Thus, the purpose of this study was to evaluate the efficacy of low-energy cooling modalities on thermoregulatory responses during physical activity in the heat. Methods: Twenty-four adults with NO-BURN (n = 9), MODERATE burns (20-40% body surface area burned, n = 7), or LARGE burns (> 40% body surface area burned, n = 8) walked for one hour at a moderate intensity (rate of metabolic heat production of 4.5 W/kg body mass) in an environmental chamber (39°C, 40% RH). Burn survivors were at least 2 years post-injury. Participants performed this activity four times, with the following modalities randomly applied throughout each trial on separate days: no cooling (i.e., control), fan at 4 m/s (FAN), water spray (WS, minimum 10-50 g every 5 min, scaled to burn area size), or WS+FAN. Core temperature (Tcore) was recorded throughout each trial via a telemetric pill. Final Tcore values for each cooling modality were compared against the no cooling condition. Results: For the LARGE burn group, WS reduced end-exercise Tcore by 0.37°C (range 0.09 to 0.66°C) compared with no cooling ( p = 0.01). FAN and WS+FAN did not impact end-exercise Tcore for the LARGE burn group ( p ≥ 0.48). No cooling modality affected Tcore for the MODERATE burn group ( p ≥ 0.12) or the NO-BURN group (p ≥ 0.55). Conclusion: At the assessed workload and environmental condition, the efficacy of the applied cooling modalities on Tcore responses for burn survivors appears to be dependent on both the selected modality and the size of the burn surface area. Namely, WS attenuated the increases in Tcore in participants with LARGE burn injuries, but FAN and WS+FAN did not attenuate Tcore responses in any group. Supported by NIHGrant R01GM068865 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Site-specific tissue lipolysis and fat metabolism differs between men and women during a treadmill-based heat tolerance test without differences in circulating biomarkers

Purpose: To test the hypothesis that measures of lipid metabolism and substrate utilization differ between men and women exposed to extreme exercise-heat stress. Methods: Physically active men (n=6, 30±8 yrs, 78.8±11.0 kg, body fat 19.4±9.8%, VO2max 49.9±2.9 mL -1· kg -1· min -1 ) and women (n=6, 25±3 yrs, 60.6±4.1 kg, 25.2±6.8%, 46.3±4.5mL -1· kg -1· min -1 ) completed a treadmill-based heat tolerance test (HTT) (2 hours, 3.1 mph, 2% grade in extreme environmental conditions (104°F, 40% relative humidity). Differences (pre-, post-, change, percentage change, mean difference (MD)) within and between groups were analyzed with nonparametric inferential statistical tests. Subcutaneous abdominal adipose tissue (SCAAT) interstitial glycerol concentration and adipose tissue blood flow (i.e., ethanol Output: Input (O:I)) pre-exercise, every 30 minutes (min) of exercise, and during recovery was measured with microdialysis and assay of biofluids. Circulating concentrations of non-esterified fatty acids (NEFAs), insulin, insulin-like growth factor (IGF-1), epinephrine (EPI), and norepinephrine (NE), and cortisol were measured with commercially available kits. Resting energy expenditure (REE) was measured pre- and post-exercise using a metabolic cart. Exercising substrate utilization and metabolic heat production (MHP) were collected during 30 and 90 mins of the HTT. Results: Despite no sex differences in markers associated with stress-related metabolic signaling (cortisol, EPI, NE), endocrine response (IGF-1, insulin), or systemic concentrations of NEFAs, fat oxidation (g·min -1 ) was higher in men (vs. women) at 30 min of HTT (men (M), women (W): 0.56±0.03, 0.45±0.05, p=0.005) and at 90 min of HTT (0.61±0.05, 0.48±0.12, p=0.05). SCAAT interstitial glycerol and O:I were similar across all time points between sexes (baseline glycerol ranges (mmol·L -1 ): 92.8-530.7 (W), 321.8-588.8 (M); O:I ratio ranges: 0.42-0.79 (W), 0.55-0.77 (M). However, women had significantly greater percent change in interstitial glycerol concentration from baseline (vs. M) (W vs. M: 275 ± 287.56% vs. -8.69 ± 32.41%, p=0.003). Pre- and post-exercise REE were 16.9% (MD:371.6 kcal·day -1 , p=0.003) and 15.5% (MD:343.5kcal·day -1 , p=0.050) lower in W compared to M. Mean MHP was higher in men (MD 85W). Conclusion: Fat oxidation and SCAAT lipolysis rates were higher in men vs. women after an acute bout of strenuous exercise-heat stress. Ongoing analyses are investigating sex, energy expenditure, and heat production contributions to differences between men and women observed in our study. Our findings suggest potential for sex-specific dietary recommendations during stress exposures. DoD BA200299, HRPO E02882.1a This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Epicore Discovery Patch® sweat collection system to assess sweat proteomics-based biomarker discovery in exercise-heat stress and acclimation

Purpose: To optimize sample processing workflow, test the hypothesis that sweat proteome expression is expansive and stress-specific, and to discover novel sweat biomarkers able to detect heat stress exposure and acclimation state. Methods: Men and women (n=5, 25.7±4.5 yrs, 66.7±10.5 kg, 69±4 inches, VO2max 49.5±4 ml×kg-1 ×min-1) completed 7 bouts of exercise in hot and humid conditions (40°C, 40% relative humidity). Parallel sweat samples (thigh) were collected on days 1 and 7 (HE1 and HE7, respectively) using the Epicore Discovery Patch® system and using gauze confined to the skin using Tegaderm. A subset of sweat samples were processed immediately vs. frozen for at least 24 hours prior to processing. ~30 ug of protein in 2% SDS in 0.1 M Tris HCl, pH 8 were reduced and alkylated (5 mM dithiothreitol, 20 mM iodoacetamide), acidified (2.5% (v/v) phosphoric acid), and subjected to the S-Trap protocol (ProtiFi, LLC) and digestion with porcine modified sequencing grade trypsin (Promega). Eluted peptides were dried, desalted, and submitted to mass spectrometry for proteomics analyses. Differential expression analyses were conducted with Scaffold and R. Results: Proteomics verified that immediately processed sweat samples yielded 213 more uniquely expressed proteins, but 188 shared proteins (vs. frozen >24 h) in presence/absence analyses, but only 1 significantly expressed protein (FDR<0.05) different between the two sample preservation protocols. In the exercise-heat stress experiments, 1,922 unique peptide sequences were detected for 2,774 unique spectra. Presence/absence analysis revealed 6 proteins uniquely present in HE1, 172 mutually present in both time points and 45 uniquely present in HE7. Based on the quantitative profile (p<0.05) of the 223 unique proteins, 13 were significantly expressed in HE7, including CD59 glycoprotein, heat shock-related 70 kDa protein 2, and aspartate aminotransferase, which have been previously linked to heat stress, although never in sweat. Conclusion: Protocol optimization reveals unique stability of Epicore Discovery Patch® sweat collection quantifiable by highly sensitive proteomics assays. Specific to a physiological heat acclimation over 7 days, stress response proteins such as various histone family members, and unique biomarkers such as CD59 glycoprotein, HSP72 and aspartate aminotransferase appeared in sweat samples. Our novel observations regarding sweat composition complexity and specific supports ongoing work with diverse subject populations and other stress conditions. ONR, DoD, Faculty IDC This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Serum klotho concentrations in older men with hypertension or type 2 diabetes during prolonged exercise in temperate and hot conditions.

Klotho is a cytoprotective protein that increases during acute physiological stressors (e.g., exercise heat stress), although age-related declines in klotho may underlie cellular vulnerability to heat stress. The present study aimed to compare serum klotho in healthy older men and men with type 2 diabetes (T2D) or hypertension (HTN) during prolonged exercise in temperate or hot conditions. We evaluated serum klotho in 12 healthy older men (mean [SD]; 59years [4]), 10 men with HTN (60years [4]), and 9 men with T2D (60years [5]) before and after 180min of moderate-intensity (fixed metabolic rate of 200 W/m2; ~ 3.4 METs) exercise and 60min of recovery in temperate (wet-bulb globe temperature (WBGT) 16°C) and hot (WBGT 32°C) environments. Core temperature (rectal), heart rate (HR), and heart rate reserve (HRR) were measured continuously while klotho was measured at the end of baseline, exercise, and recovery. Total exercise duration was reduced during the hot condition in older men with HTN and T2D than healthy older men (both p ≤ 0.049), despite similar core temperatures, HR, and HRR. Klotho was higher than rest following exercise in the heat in healthy older men (+ 191pg/mL [189]; p < 0.001) and responses were greater (p = 0.036) than men with HTN (+ 118pg/mL [49]; p = 0.030), although klotho did not increase in men with T2D (+ 4pg/mL [71]; p ≥ 0.638). Given klotho's role in cytoprotection, older men with HTN and especially T2D may be at increased cellular vulnerability to prolonged exercise or physically demanding exercise in the heat.

Association between haemoglobin A1c and whole-body heat loss during exercise-heat stress in physically active men with type 2 diabetes.

What is the central question of this study? Is the impairment in heat dissipation during exercise observed in men with type 2 diabetes related to glycaemic control (indexed by glycated haemoglobin; haemoglobin A1c )? What is the main finding and its importance? No association was found between haemoglobin A1c (range: 5.1-9.1%) and whole-body heat loss in men with type 2 diabetes during exercise in the heat. However, individuals with elevated haemoglobin A1c exhibited higher body core temperature and heart rate responses. Thus, while haemoglobin A1c is not associated with heat loss per se, it may still have important implications for physiological strain during exercise. Type 2 diabetes is associated with a reduced capacity to dissipate heat. It is unknown whether this impairment is related to glycaemic control (indexed by glycated haemoglobin; haemoglobin A1c ) is unknown. We evaluated the association between haemoglobin A1c and whole-body heat loss (via direct calorimetry), body core temperature, and heart rate in 26 physically active men with type 2 diabetes (43-73 years; HbA1c 5.1-9.1%) during exercise at increasing rates of metabolic heat production (∼150, 200, 250Wm-2 ) in the heat (40°C, ∼17% relative humidity). Haemoglobin A1c was not associated with whole-body heat loss (P=0.617), nor the increase in core temperature from pre-exercise (P=0.347). However, absolute core temperature and heart rate were elevated ∼0.2°C (P=0.014) and ∼6beatsmin-1 (P=0.049), respectively, with every percentage point increase in haemoglobin A1c . Thus, while haemoglobin A1c does not appear to modify diabetes-related reductions in capacity for heat dissipation, it may still have important implications for physiological strain during exercise-heat stress.

Dynamic Relationship Between Heart Rate And Core Temperature During Exercise-heat Stress And Iced Sheet Cooling

Athletes, military personnel, and others who perform physical work in the heat are at risk for exertional heat illness due to the combined presence of high ambient temperature and elevated metabolic heat production. Cooling with iced sheets is an immediate treatment used by the military and others to rapidly decrease body temperature in a field setting. Physiologically, increases in core temperature (Tc) and heart rate (HR) contribute to the cardiovascular strain associated with exercising in the heat. This increased HR is linked to the combination of metabolic (exercise) and thermal (environmental) requirements for systemic blood flow (i.e. cardiac output). Mechanisms include both autonomic neural and local influences of temperature on the heart. PURPOSE: To quantify the dynamic response of HR to changes in Tc during exercise in the heat and subsequent iced sheet cooling. We hypothesized that for a given Tc, HR would be higher during increases in Tc compared to during decreases in Tc. METHODS: Nine healthy (n = 8 males) volunteers (age 25 ± 6 y, ht 176.9 ± 9.7 cm, wt 86.6 ± 15.9 kg, body surface area 2.03 ± 0.2 m2) participated in a exercise-heat stress protocol consisting of up to 180 minutes of treadmill walking (3.5 mi·hr-1, 5% grade, in 40 °C, 30% RH). Volunteers then lay supine and underwent iced-sheet cooling (ISC) (bed sheets placed in 5-gallon ice buckets with 2/3 ice, 1/3 cool water; rotated out with pre-soaked sheets every 3 min) until Tc decreased to ≤38.0 °C. Individual changes in HR during both exercise and cooling were compared at Tc = 38.2 and 38.6 °C using 2-way analysis of variance. RESULTS: HR was significantly higher for a given Tc when Tc was increasing during exercise compared to when it was decreasing during cooling. For example, during exercise, HR was 150 ± 13 bpm at Tc = 38.2 °C and 157 ± 9 bpm at Tc = 38.6 °C, while during cooling, HR was 96 ± 10 bpm at Tc = 38.2 °C and 104 ± 14 bpm at Tc = 38.6 °C (both p < 0.01). CONCLUSION: These data confirm the efficacy of iced-sheet cooling for decreasing cardiovascular strain associated with heat-related events. The fact that cooling resulted in lower HR for a given Tc suggests that exercise associated autonomic reflexes predominated over direct effects of temperature on sinus node control of HR. Supported by USAMRDC; author views not official US Army or DoD policy.

Influence of sex and biological maturation on the sudomotor response to exercise-heat stress: are girls disadvantaged?

Both adult females and children have been reported to have a lower sweating capacity and thus reduced evaporative heat loss potential that may increase their susceptibility to exertional hyperthermia in the heat. Compared with males, females have a lower maximal sweat rate and thus a theoretically lower maximum skin wettedness due to a lower sweat output per gland. Similarly, children have been suggested to be disadvantaged in high ambient temperatures due to a lower sweat production and therefore reduced evaporative capacity, despite modifications of heat transfer due to physical attributes and possible evaporative efficiency. The reported reductions in the sudomotor activity of females and children suggest a lower sweating capacity in girls. However, because of the complexities of isolating sex and maturation from the confounding effects of morphological differences (e.g., body surface area-to-mass ratio) and metabolic heat production, limited evidence exists supporting whether children, and, more specifically, girls are at a thermoregulatory disadvantage. Furthermore, a limited number of child-adult comparison studies involve females and very few studies have directly compared regional and whole body sudomotor activity between boys and girls. This minireview highlights the exercise-induced sudomotor response of females and children, summarizes previous research investigating the sudomotor response to exercise in girls, and suggests important areas for further research.

The effect of acute intradermal administration of ascorbate on heat loss responses in older adults with uncomplicated controlled hypertension.

What is the central question of this study? Does acute intradermal administration of the antioxidant ascorbate augment local forearm cutaneous vasodilatation and sweating via nitric oxide synthase (NOS)-dependent mechanisms during exercise-heat stress in older adults with uncomplicated controlled hypertension? What is the main finding and its importance? Relative to the control site, ascorbate had no effect on forearm cutaneous vascular conductance (CVC) and sweat rate, although CVC was reduced with NOS inhibition in older adults with hypertension. Acute local administration of ascorbate to forearm skin does not modulate heat loss responses during exercise-heat stress in older adults with hypertension. Nitric oxide synthase (NOS) contributes to the heat loss responses of cutaneous vasodilatation and sweating during exercise. However, the contribution of NOS may be attenuated in individuals with uncomplicated, controlled hypertension due to elevated oxidative stress, which can reduce NO bioavailability. We evaluated the hypothesis that the acute local intradermal administration of the antioxidant ascorbate would enhance cutaneous vasodilatation and sweating via NOS-dependent mechanisms during an exercise-heat stress in adults with hypertension. Habitually active adults who were normotensive (n=14, 7 females, 62±4years) or had uncomplicated, controlled hypertension (n=13, 6 females, 62±5years) performed 30min of moderate-intensity (50% of their pre-determined peak oxygen uptake) semi-recumbent cycling in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC) and sweat rate were assessed at four forearm skin sites continuously perfused with (1) lactated Ringer solution (Control), (2) 10mM antioxidant ascorbate, (3) 10mMNG -nitro-l-arginine methyl ester (l-NAME), a non-selective NOS inhibitor, or (4) a combination of ascorbate and l-NAME. Relative to Control, no effect of ascorbate was observed on CVC or sweating in either group (P=0.619). However, l-NAME reduced CVC relative to Control in both groups (P≤0.038). No effect of any treatment on sweating was observed (P≥0.306). Thus, acute local administration of ascorbate to forearm skin does not enhance the activation of heat loss responses of cutaneous vasodilatation and sweating in older adults, and those with hypertension during an exercise-heat stress.

The Autophagic Response to Passive and Exercise‐induced Increases in Body Core Temperature in Young Adults

Autophagy is an essential cellular survival mechanism that involves the degradation and recycling of aged or damaged organelles and protein aggregates to maintain cellular homeostasis. While autophagic dysfunction occurs with aging and is associated with many disease‐related pathologies, methods to modulate autophagic activity remain poorly understood in the context of human physiology. Recently, we demonstrated that autophagy is activated in an intensity‐dependent manner during both exercise and passive heat stress, however it is unknown if the autophagic response to elevations in body core temperature (Tcore) during passive heat exposure are comparable to those elicited through exercise. Therefore, we sought to assess the autophagic response to an elevated state of hyperthermia associated with intense exercise and compare responses to a similar rate and magnitude of increase in Tcore elicited through warm water immersion (WI). We evaluated the hypothesis that autophagic stimulation would occur during both exercise and WI, although responses would be greater during the exercise bout. To assess this hypothesis, 6 young men (mean [SD] 23 [3] years) performed 30 min of intense (70% of maximal oxygen consumption (VO2max)) semi‐recumbent cycling. On a separate day (at least 72h after the exercise bout), the same participants were immersed in warm water (up to the clavicle) for 30 min, with the water temperature adjusted to elicit the same relative increase in Tcore (as estimated by rectal temperature) as was achieved during the prior exercise session. Given Tcore during WI was matched to the prior exercise bout, all WI trials were conducted after the exercise session. Autophagic activity was assessed in peripheral blood mononuclear cells prior to, immediately post‐exercise or WI, and following a seated recovery (3 and 6h). Western blot was used to assess changes in autophagy via microtubule‐associated light chain 3 beta (LC3‐II) and normalized to β‐actin (expressed as relative fold change to the respective baseline). Area under the curve was used to assess the Tcore response between conditions and protein data were analyzed via a two‐way repeated measures ANOVA with Fisher’s LSD (α=0.05). A similar average relative increase in Tcore was observed during the exercise and WI bouts (0.65 [0.21]°C vs 0.61 [0.19]°C, respectively; p=0.80) with a return to baseline within 3h in both conditions. In response to 30‐min of exercise, LC3‐II significantly increased immediately after exercise (1.69 [0.12]; p&lt;0.01) and remained elevated above baseline at 3h (1.51 [0.23]; p&lt;0.01) and 6h (1.38 [0.16]; p&lt;0.01). A similar pattern of response was observed following WI (1.86 [0.77]; p=0.04), however, LC3‐II returned to pre‐WI levels within the first 3h of recovery. Our preliminary findings show similar increases in autophagy following a similar elevation in core temperature associated induced by exercise and WI. However, the autophagic response only remained elevated after exercise, likely caused by exercise‐associated metabolic perturbations. Further research is warranted to delineate the underlying pathways of autophagic activation during these different thermal stressors.

Effects of sex and wet-bulb globe temperature on heart rate variability during prolonged moderate-intensity exercise: a secondary analysis.

Sex differences in heart rate (HR) and heart rate variability (HRV), a surrogate of cardiac autonomic modulation, are evident during rest and exercise in young healthy individuals. However, it remains unclear whether sex impacts HRV during prolonged exercise at differing levels of environmental heat stress. Therefore, we completed a secondary analysis upon the effects of sex and wet-bulb globe temperature (WBGT) on HR and HRV during prolonged exercise. To achieve this, HR and HRV were assessed in non-endurance-trained and non-heat-acclimatised healthy men (n=19) and women (n=15) aged 18-45 years during 180min of treadmill walking at a moderate metabolic rate (200W/m2: equivalent to ∼35% peak aerobic power) in 16, 24, 28, and 32°C WBGT. In the final 5min prior to exercise termination, HR was observed to be higher in women relative to men in all but the 32 °C WBGT. Although no sex differences were observed for the HRV metric of root-mean-square of successive differences, high-frequency power was higher in women relative to men across WBGT conditions. These findings indicate that, in healthy non-heat-acclimatised individuals, women respond to prolonged exercise-heat stress with a greater increase in HR despite cardiac vagal autonomic modulation remaining equal or increasing compared to men. Novelty: Prior to exercise termination, females respond with a greater increase in HR under all WBGTs except the hottest (32 °C). Sexinfluenced HRV metrics during all WBGTs, but results were mixed. Further characterisation of HRV sex differences remains an important area of research.

The impact of age, type 2 diabetes and hypertension on heart rate variability during rest and exercise at increasing levels of heat stress.

In older adults with type 2 diabetes (T2D) and hypertension (HTN), cardiac autonomic modulation is markedly attenuated during exercise-heat stress. However, the extent to which this impairment is evident under increasing levels of heat stress remains unknown. We examined heart rate variability (HRV), a surrogate of cardiac autonomic modulation, during incremental exercise-heat stress exposures in young (20-30years) and middle-aged-to-older individuals (50-70years) without and with T2D and HTN. Thirteen young and healthy (Young, n = 13) and 37 older men without (Older, n = 14) and with HTN (n = 13) or T2D (n = 10) performed 180-min treadmill walking at a fixed metabolic rate (~ 200W/m2; ~ 3.5 METs) in a differing wet-bulb globe temperature (WBGT; 16°C, 24°C, 28°C, and 32°C). Electrocardiogram (ECG) and core temperature measurements were recorded throughout. Data were analysed using 5-min averaged epochs following 60-min exercise, which represented the last common timepoint across groups and conditions. Ageing did not significantly reduce HRV during increasing exercise-heat stress (all p > 0.050). However, T2D and HTN modified HRV during exercise-heat stress such that Detrended Fluctuation Analysis (DFA) α1 (p = 0.012) and the cardiac sympathetic index (p = 0.037) were decreased compared to Older in all except the warmest WBGT condition (32°C). Our unique observations indicate that, relative to their younger counterparts, HRV in healthy older individuals is not perturbed during exercise heat-stress. However, relative to their age-matched healthy counterparts, HRV is reduced during exercise-heat stress in individuals with age-associated chronic conditions, indicative of cardiac autonomic dysfunction.

The combined effects of exercise-induced muscle damage and heat stress on acute kidney stress and heat strain during subsequent endurance exercise.

The purpose of the study was to investigate the combined effect of downhill running and heat stress on muscle damage, as well as on heat strain and kidney stress during subsequent running in the heat. In a randomized cross-over study, ten non-heat-acclimated, physically active males completed downhill running in temperate (EIMD in Temp) and hot (EIMD in Hot) conditions followed by an exercise-heat stress (HS) test after 3-h seated rest. Blood and urine samples were collected immediately pre- and post-EIMD and HS, and 24h post-EIMD (post-24h). Core temperature and thermal sensation were measured to evaluate heat strain. Serum creatine kinase (CK), maximal voluntary isometric contraction of the quadriceps (MVC) and perceived muscle soreness were measured to evaluate muscle damage. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) levels were measured to indicate acute kidney stress. CK, MVC and perceived soreness were not different between conditions at any timepoints. In the EIMD in Hot condition, urinary NGAL was significantly elevated from pre- to post-HS (pre-HS: 6.56 {1.53-12.24}ng/min, post-HS: 13.72 {7.67-21.46}ng/min, p = 0.034). Such elevation of NGAL or KIM-1 was not found in the EIMD in Temp condition. As compared with downhill running in a temperate environment, downhill running in a hot environment does not appear to aggravate muscle damage. However, elevated NGAL levels following EIMD in a hot environment suggest such exercise may increase risk of mild acute kidney injury during subsequent endurance exercise in the heat.

Heat shock protein response during fixed intensity and self-paced exercise in the heat in young, healthy women on oral contraceptives compared with young healthy men.

Heat shock proteins respond to a variety of physiological and environmental stresses, including heat stress, ischemia and endotoxic shock. Hormonal changes during the female menstrual cycle can have a thermogenic effect on body temperature. The monophasic oral contraceptive (OC) pill provides low doses of progesterone and oestrogen over the course of the normal menstrual phase. There is little evidence regarding the combined effects of OC on exercise performance and heat stress with respect to heat shock protein response. This study aimed to determine the response of heat shock proteins (Hsp72) during fixed-intensity and self-paced exercise in the heat in young, healthy women on oral contraceptives compared with young healthy men. Sixteen physically active men and women performed 30 min fixed-intensity cycling at 50% of maximum workload, followed by 30 min of a self-paced time trial (TT) interspersed by 30 s maximal sprint at 9, 19 and 29 min respectively. Trials were undertaken in cool (20°C; 48±3% relative humidity (RH)) and warm (32°C; 66±2% RH) ambient conditions. Core (T c) and skin temperature, heart rate (HR) and subjective responses were measured before, during and post exercise. The distance, mean and peak power output, mean and peak speed during the self-paced time trial showed no difference between the ambient temperatures for men and women. Hsp72 in females was higher than males at all sample points at both 20°C and 32°C, except for pre-exercise at 20°C (p< 0.04). Women also attained a higher T c than men at the end of the TT in the heat (38.5°C v 37.9°C for women and men, respectively; p<0.03), higher mean HR and perceived exertion. This study indicates that females who use oral contraceptives (OC) had higher levels of Hsp72 than males when tested under the same environmental conditions.

Therapeutic effects of novel type1 ryanodine receptor inhibitor on skeletal muscle diseases

Type 1 ryanodine receptor (RyR1) plays a key role in Ca2+ release from the sarcoplasmic reticulum (SR) during excitation-contraction coupling of skeletal muscle. Mutations in RyR1 hyperactivate the channel to cause malignant hyperthermia (MH). MH is a serious complication characterized by skeletal muscle rigidity and elevated body temperature in response to commonly used inhalational anesthetics. Thus far, more than 300 mutations in RyR1 gene have been reported in patients with MH. Some heat stroke triggered by exercise or environmental heat stress is also related to MH mutations in the RyR1 gene. The only drug approved for ameliorating the symptoms of MH is dantrolene, which has been first developed in 1960s as a muscle relaxant. However, dantrolene has several disadvantages for clinical use: poor water solubility which makes rapid preparation difficult in emergency situations and long plasma half-life, which causes long-lasting side effects such as muscle weakness. Here we show that a novel RyR1-selective inhibitor, 6,7-(methylenedioxy)-1-octyl-4-quinolone-3-carboxylic acid (Compound 1, Cpd1), effectively rescues MH and heat stroke in new mouse model relevant to MH. Cpd1 has great advantages of higher water solubility and shorter plasma half-life compared to dantrolene. Our data suggest that Cpd1 has the potential to be a promising new candidate for effective treatment of patients carrying RyR1 mutations.

A 32-day long fieldwork in Antarctica improves heat tolerance during physical exercise.

We evaluated the influence of a 32-day camping in Antarctica on physical performance and exercise-induced thermoregulatory responses. In Brazil, before and after the Antarctic camping, the volunteers performed an incremental exercise at temperate conditions and, two days later, an exercise heat stress protocol (45-min running at 60% of maximum aerobic speed, at 31°C and 60% of relative humidity). In Antarctica, core temperature was assessed on a day of fieldwork, and average values higher than 38.5°C were reported. At pre- and post-Antarctica, physiological (whole-body and local sweat rate, number of active sweat glands, sweat gland output, core and skin temperatures) and perceptual (thermal comfort and sensation) variables were measured. The Antarctic camping improved the participants' performance and induced heat-related adaptations, as evidenced by sweat redistribution (lower in the chest but higher in grouped data from the forehead, forearm, and thigh) and reduced skin temperatures in the forehead and chest during the exercise heat stress protocol. Notwithstanding the acclimatization, the participants did not report differences of the thermal sensation and comfort. In conclusion, staying in an Antarctic camp for 32 days improved physical performance and elicited physiological adaptations to heat due to the physical exertion-induced hyperthermia in the field.

Exercise-Heat Stress, Hyperthermia, Dehydration and Fatigue Effects on Cognitive Performance among Semi-Professional Male Athletes

Background: Evidence regarding heat stress, dehydration, hypohydration and fluid balance effects on semi-professional athletes’ cognitive function is still limited. This study aimed to examine the effects of exercise heat-stress, hyperthermia, dehydration and fatigue on cognitive performances in semi-professional athletes. Methods: Eighteen healthy male athletes from individual and team sports participated. Participants completed a cognitive and mood test battery prior, immediately after and post 120 min of treadmill exercise. A soccer-specific intermittent treadmill exercise protocol was completed in four experimental trials in temperate (normothermic) and hot (hyperthermic) conditions. Participants were hydrated and dehydrated in both conditions. Trial conditions were; normothermic 16.4 ± 0.02°C and 52 ± 1% RH, while hyperthermic 33.9 ± 0.3°C and 61 ± 1% RH. Results: Response times; the Stroop effect and Visual search tasks were quicker (584 to 690 ms, p= 0.001; 1978 to 2213 ms, p= 0.003) in the heat. Cognitive tasks showed that reaction time, visual process, motor speed and mood were similar in normothermic (p=0.001). Accuracy improved in hydrated hyperthermic by 1.2% (p=0.002) in Visual search. Total Mood Disturbance was significant in heat (p&lt;0.001). Hydration status had no major effect in some cognition performance markers except for mood. Conclusion: The response times and accuracy improved following the cognitive testing in semi-professional athletes exercising in relatively humid, hot conditions. However, semi-professional athletes’ cognitive performances were relatively affected by hypohydration and their hydration status needs to be closely monitored during exercise.

Therapeutic effects of novel type 1 ryanodine receptor inhibitor on malignant hyperthermia

Ca2+-induced Ca2+ release (CICR) is mediated by ryanodine receptors, a Ca2+ release channel in the sarcoplasmic/endoplasmic reticulum (SR/ER), and plays an important role in various tissues. Type 1 ryanodine receptor (RYR1) plays a key role during excitation-contraction coupling of skeletal muscle. Mutations in RYR1 overactivate the channel to cause malignant hyperthermia (MH). MH is a serious complication characterized by skeletal muscle rigidity and elevated body temperature in response to commonly used inhalational anesthetics. Thus far, >300 mutations in the RYR1 gene have been reported in patients with MH. Some heat stroke triggered by exercise or environmental heat stress is also related to MH mutations in the RYR1 gene. The only drug approved for ameliorating the symptoms of MH is dantrolene, which has been first developed in the 1960s as a muscle relaxant. However, dantrolene has several disadvantages for clinical use: poor water solubility, which makes rapid preparation difficult in emergency situations, and long plasma half-life, which causes long-lasting side effects such as muscle weakness. Here, we show that a novel RYR1-selective inhibitor, 6,7-(methylenedioxy)-1-octyl-4-quinolone-3-carboxylic acid (compound 1 [Cpd1]), effectively rescues MH and heat stroke in new mouse model (RYR1-p.R2509C) relevant to MH. Cpd1 has great advantages of higher water solubility and shorter plasma half-life compared with dantrolene. Our data suggest that Cpd1 has the potential to be a promising new candidate for effective treatment of patients carrying RYR1 mutations. Finally, we have recently identified that heat directly activates RYR1, which induces Ca2+ release from intracellular stores. Our results provide direct evidence that heat induces Ca2+ release (HICR) from the SR through the mutants rather than wild type RYR1, causing an immediate rise in the cytosolic Ca2+ concentration.

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

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 (Posm) 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 •103]). 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.