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We tested the hypothesis that, compared with normothermia, the increase in glomerular filtration rate (GFR) after an oral protein load (defined as the GFR reserve) is attenuated during moderate passive heat stress in young healthy adults. Sixteen participants (5 women; 26 ± 2 yr) completed two experimental visits, heat stress or a normothermic time-control, assigned in a block-randomized crossover design. During the heat stress trial, core temperature was increased by 0.6°C in the first hour before commencing a 2-min cold pressor test (CPT) to assess renal vasoconstrictor responses. One-hour post-CPT, subjects ingested a whey protein shake (1.2 g of protein/kg body wt), and measurements were taken pre-, 75, and 150 min postprotein. Segmental artery vascular resistance was calculated as the quotient of Doppler ultrasound-derived segmental artery blood velocity and mean arterial pressure and provided an estimate of renal vascular tone. GFR was estimated from creatinine clearance. The increase in segmental artery vascular resistance during the CPT was attenuated during heat stress (end CPT: 5.6 ± 0.9 vs. 4.7 ± 1.1 mmHg/cm/s, P = 0.024). However, the reduction in segmental artery vascular resistance in response to an oral protein load did not differ between heat stress (at 150 min: 1.9 ± 0.4 mmHg/cm/s) and normothermia (at 150 min: 1.8 ± 0.5 mmHg/cm/s; P = 0.979). The peak increase in creatinine clearance postprotein, independent of time, was attenuated during heat stress (+26 ± 19 vs. +16 ± 20 mL/min, P = 0.013, n = 13). GFR reserve is diminished by mild passive heat stress. Moreover, renal vasoconstrictor responses are attenuated by mild passive heat stress, but renal vasodilator responses are maintained.

Occupational heat exposure is linked to the development of kidney injury and disease in individuals who frequently perform physically demanding work in the heat. For instance, in Central America, an epidemic of chronic kidney disease of nontraditional origin (CKDnt) is occurring among manual laborers, whereas potentially related epidemics have emerged in India and Sri Lanka. There is growing concern that workers in the United States suffer with CKDnt, but reports are limited. One of the leading hypotheses is that repetitive kidney injury caused by physical work in the heat can progress to CKDnt. Whether heat stress is the primary causal agent or accelerates existing underlying pathology remains contested. However, the current evidence supports that heat stress induces tubular kidney injury, which is worsened by higher core temperatures, dehydration, longer work durations, muscle damaging exercise, and consumption of beverages containing high levels of fructose. The purpose of this narrative review is to identify occupations that may place US workers at greater risk of kidney injury and CKDnt. Specifically, we reviewed the scientific literature to characterize the demographics, environmental conditions, physiological strain (i.e., core temperature increase, dehydration, heart rate), and work durations in sectors typically experiencing occupational heat exposure, including farming, wildland firefighting, landscaping, and utilities. Overall, the surprisingly limited available evidence characterizing occupational heat exposure in US workers supports the need for future investigations to understand this risk of CKDnt.

INTRODUCTION We tested the hypothesis that people with multiple sclerosis (MS) who experience heat sensitivity voluntarily engage in cool-seeking behavior during exercise to a greater extent than healthy controls. METHODS In a 27.0°C ± 0.2°C, 41% ± 2% RH environment, seven participants with relapsing-remitting MS who exhibited heat sensitivity and seven healthy controls completed two randomized trials cycling for 40 min (EX) at 3.5 W·kg-1 metabolic heat production, followed by 30 min recovery (REC). In one trial, participants were restricted from engaging in cooling (CON). In the other trial, participants voluntarily pressed a button to receive 2 min of ~2°C water perfusing a top (COOL). Mean skin and core temperatures and mean skin wettedness were recorded continuously. Total time in cooling provided an index of cool-seeking behavior. RPE, total symptom scores (MS only), and subjective fatigue (MS only) were recorded every 10 min. RESULTS Core temperature (+0.5°C ± 0.1°C) and skin wettedness (+0.53 ± 0.02 a.u.) increased but were not different between groups or trials at end exercise (P = 0.196) or end recovery (P = 0.342). Mean skin temperature was reduced in COOL compared with CON at end exercise (P ≤ 0.002), with no differences between groups (P ≥ 0.532). MS spent more total time in cooling during EX (MS, 13 ± 3 min; healthy, 7 ± 4 min; P < 0.001) but not REC (MS, 2 ± 1 min; healthy, 0 ± 1 min; P = 0.496). RPE was greater at end exercise in MS (P = 0.001). Total symptom scores increased during exercise (P = 0.005) but was not different between trials (P = 0.321), whereas subjective fatigue was not attenuated in the cooling trial (P = 0.065). CONCLUSION Voluntary cooling is augmented in MS but does not consistently mitigate perceptions of heat-related symptoms or subjective fatigue.

In healthy humans, fructose-sweetened water consumption increases blood pressure variability (BPV) and decreases spontaneous cardiovagal baroreflex sensitivity (cBRS) and heart rate variability (HRV). However, whether consuming commercially available soft drinks containing high levels of fructose elicits similar responses is unknown. We hypothesized that high-fructose corn syrup (HFCS)-sweetened soft drink consumption increases BPV and decreases cBRS and HRV to a greater extent compared with artificially sweetened (diet) and sucrose-sweetened (sucrose) soft drinks and water. Twelve subjects completed four randomized, double-blinded trials in which they drank 500 mL of water or commercially available soft drinks matched for taste and caffeine content. We continuously measured beat-to-beat blood pressure (photoplethysmography) and R-R interval (ECG) before and 30 min after drink consumption during supine rest for 5 min during spontaneous and paced breathing. BPV was evaluated using standard deviation (SD), average real variability (ARV), and successive variation (SV) methods for systolic and diastolic blood pressure. cBRS was assessed using the sequence method. HRV was evaluated using the root mean square of successive differences (RMSSD) in R-R interval. There were no differences between conditions in the magnitude of change from baseline in SD, ARV, and SV ( P ≥ 0.07). There were greater reductions in cBRS during spontaneous breathing in the HFCS (−3 ± 5 ms/mmHg) and sucrose (−3 ± 5 ms/mmHg) trials compared with the water trial (+1 ± 5 ms/mmHg, P < 0.03). During paced breathing, HFCS evoked greater reductions in RMSSD compared with water (−26 ± 34 vs. +2 ± 26 ms, P < 0.01). These findings suggest that sugar-sweetened soft drink consumption alters cBRS and HRV but not BPV.

We first tested the hypothesis that consuming a high-fructose corn syrup (HFCS)-sweetened soft drink augments kidney vasoconstriction to sympathetic stimulation compared with water ( study 1). In a second study, we examined the mechanisms underlying these observations ( study 2). In study 1, 13 healthy adults completed a cold pressor test, a sympathoexcitatory maneuver, before (preconsumption) and 30 min after drinking 500 mL of decarbonated HFCS-sweetened soft drink or water (postconsumption). In study 2, venous blood samples were obtained in 12 healthy adults before and 30 min after consumption of 500 mL water or soft drinks matched for caffeine content and taste, which were either artificially sweetened (Diet trial), sucrose-sweetened (Sucrose trial), or sweetened with HFCS (HFCS trial). In both study 1 and study 2, vascular resistance was calculated as mean arterial pressure divided by blood velocity, which was measured via Doppler ultrasound in renal and segmental arteries. In study 1, HFCS consumption increased vascular resistance in the segmental artery at rest (by 0.5 ± 0.6 mmHg·cm−1·s−1, P = 0.01) and during the cold pressor test (average change: 0.5 ± 1.0 mmHg·cm−1·s−1, main effect: P = 0.05). In study 2, segmental artery vascular resistance increased in the HFCS trial (by 0.8 ± 0.7 mmHg·cm−1·s−1, P = 0.02) but not in the other trials. Increases in serum uric acid were greater in the HFCS trial (0.3 ± 0.4 mg/dL, P ≤ 0.04) compared with the Water and Diet trials, and serum copeptin increased in the HFCS trial (by 0.8 ± 1.0 pmol/L, P = 0.06). These findings indicate that HFCS acutely increases vascular resistance in the kidneys, independent of caffeine content and beverage osmolality, which likely occurs via simultaneous elevations in circulating uric acid and vasopressin.

Profound increases (>15 mmHg) in arterial carbon dioxide (i.e., hypercapnia) reduce renal blood flow. However, a relatively brief and mild hypercapnia can occur in patients with sleep apnea or in those receiving supplemental oxygen therapy during an acute exacerbation of chronic obstructive pulmonary disease. We tested the hypothesis that a brief, mild hypercapnic exposure increases vascular resistance in the renal and segmental arteries. Blood velocity in 14 healthy adults (26 ± 4 yr; 7 women, 7 men) was measured in the renal and segmental arteries with Doppler ultrasound while subjects breathed room air (Air) and while they breathed a 3% CO2, 21% O2, 76% N2 gas mixture for 5 min (CO2). The end-tidal partial pressure of CO2 ([Formula: see text]) was measured via capnography. Mean arterial pressure (MAP) was measured beat to beat via the Penaz method. Vascular resistance in the renal and segmental arteries was calculated as MAP divided by blood velocity. [Formula: see text] increased with CO2 (Air: 45 ± 3, CO2: 48 ± 3 mmHg, P < 0.01), but there were no changes in MAP ( P = 0.77). CO2 decreased blood velocity in the renal (Air: 35.2 ± 8.1, CO2: 32.2 ± 7.3 cm/s, P < 0.01) and segmental (Air: 24.2 ± 5.1, CO2: 21.8 ± 4.2 cm/s, P < 0.01) arteries and increased vascular resistance in the renal (Air: 2.7 ± 0.9, CO2: 3.0 ± 0.9 mmHg·cm−1·s, P < 0.01) and segmental (Air: 3.9 ± 1.0, CO2: 4.4 ± 1.0 mmHg·cm−1·s, P < 0.01) arteries. These data provide evidence that the kidneys are hemodynamically responsive to a mild and acute hypercapnic stimulus in healthy humans.

To optimize study design and data interpretation, there is a need to understand the reliability of Doppler ultrasound-derived measures of blood velocity (BV) measured in the renal and segmental arteries. Thus, this study tested the following two hypotheses: 1) renal and segmental artery BV measured over the current standard of three cardiac cycles have good agreement with measurements over nine cardiac cycles ( study 1); and 2) renal and segmental artery BV measurements have relatively poor day-to-day reliability ( study 2). In study 1, there was excellent agreement between measurements over three and nine cardiac cycles for BV in both the renal and segmental arteries, as evidenced by BV measurements that were not statistically different ( P ≥ 0.68), were highly consistent ( r ≥ 0.99, P < 0.01), had a coefficient of variation ≤2.5 ± 1.8%, and 97% (renal artery) and 92% (segmental artery) of the individual differences fell within the 95% limits of agreement. In study 2, there was relatively good day-to-day reliability in renal artery BV as evidenced by no differences between three separate days ( P ≥ 0.30), an intraclass correlation coefficient (ICC) of 0.92 (0.78, 0.98), and 7.4 ± 5.5% coefficient of variation. The day-to-day reliability was relatively poor in the segmental artery with an ICC of 0.77 (0.41, 0.93) and 9.0 ± 5.6% coefficient of variation. These findings support measuring renal and segmental artery hemodynamics over three cardiac cycles and the utility in reporting renal BV across days. However, because of the variation across days, hemodynamic responses in the segmental arteries should be reported as changes from baseline when making comparisons across multiple days. NEW & NOTEWORTHY The present study indicates that Doppler ultrasound-derived measures of renal and segmental artery hemodynamics over three cardiac cycles have excellent agreement with those over nine cardiac cycles. These findings support the current practice of measuring renal and segmental artery blood velocity over three cardiac cycles. This study also demonstrates that there is excellent day-to-day reliability for measures of renal artery blood velocity, which supports reporting absolute values of renal artery blood velocity across days. However, it was also found that the day-to-day reliability of segmental artery measurements is relatively poor. Thus, to account for this variability, we suggest that segmental artery hemodynamics be compared as relative changes from baseline across separate days.

Wet bulb temperatures (T(wet)) during extreme heat events are commonly 31°C. Recent predictions indicate that T(wet) will approach or exceed 34°C. Epidemiological data indicate that exposure to extreme heat events increases kidney injury risk. We tested the hypothesis that kidney injury risk is elevated to a greater extent during prolonged exposure to T(wet) = 34°C compared with T(wet) = 31°C. Fifteen healthy men rested for 8 h in T(wet) = 31 (0)°C and T(wet) = 34 (0)°C. Insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinase 2 (TIMP-2), and thioredoxin 1 (TRX-1) were measured from urine samples. The primary outcome was the product of IGFBP7 and TIMP-2 ([IGFBP7·TIMP-2]), which provided an index of kidney injury risk. Plasma interleukin-17a (IL-17a) was also measured. Data are presented at preexposure and after 8 h of exposure and as mean (SD) change from preexposure. The increase in [IGFBP7·TIMP-2] was markedly greater at 8 h in the 34°C [+26.9 (27.1) (ng/mL)(2)/1,000) compared with the 31°C [+6.2 (6.5) (ng/mL)(2)/1,000] trial (P < 0.01). Urine TRX-1, a marker of renal oxidative stress, was higher at 8 h in the 34°C [+77.6 (47.5) ng/min] compared with the 31°C [+16.2 (25.1) ng/min] trial (P < 0.01). Plasma IL-17a, an inflammatory marker, was elevated at 8 h in the 34°C [+199.3 (90.0) fg/dL; P < 0.01] compared with the 31°C [+9.0 (95.7) fg/dL] trial. Kidney injury risk is exacerbated during prolonged resting exposures to T(wet) experienced during future extreme heat events (34°C) compared with that experienced currently (31°C), likely because of oxidative stress and inflammatory processes. NEW AND NOTEWORTHY We have demonstrated that kidney injury risk is increased when men are exposed over an 8-h period to a wet bulb temperature of 31°C and exacerbated at a wet bulb temperature of 34°C. Importantly, these heat stress conditions parallel those that are encountered during current (31°C) and future (34°C) extreme heat events. The kidney injury biomarker analyses indicate both the proximal and distal tubules as the locations of potential renal injury and that the injury is likely due to oxidative stress and inflammation.

There has been a surge of studies published in the last 10 y examining the potential for pathology related to exercise (or physical work) in the heat and the kidneys. For instance, a PubMed search ...

We tested the hypothesis that thermal behavior resulting in reductions in mean skin temperature alleviates thermal discomfort and mitigates the rise in core temperature during light-intensity exercise. In a 27 ± 0°C, 48 ± 6% relative humidity environment, 12 healthy subjects (6 men, 6 women) completed 60 min of recumbent cycling. In both trials, subjects wore a water-perfused suit top continually perfusing 34 ± 0°C water. In the behavior trial, subjects maintained their upper body thermally comfortable by pressing a button to perfuse cool water (2.2 ± 0.5°C) through the top for 2 min per button press. Metabolic heat production (control: 404 ± 52 W, behavior: 397 ± 65 W; P = 0.44) was similar between trials. Mean skin temperature was reduced in the behavior trial (by −2.1 ± 1.8°C, P < 0.01) because of voluntary reductions in water-perfused top temperature ( P < 0.01). Whole body ( P = 0.02) and local sweat rates were lower in the behavior trial ( P ≤ 0.05). Absolute core temperature was similar ( P ≥ 0.30); however, the change in core temperature was greater in the behavior trial after 40 min of exercise ( P ≤ 0.03). Partitional calorimetry did not reveal any differences in cumulative heat storage (control: 554 ± 229, behavior: 544 ± 283 kJ; P = 0.90). Thermal behavior alleviated whole body thermal discomfort during exercise (by −1.17 ± 0.40 arbitrary units, P < 0.01). Despite lower evaporative cooling in the behavior trial, similar heat loss was achieved by voluntarily employing convective cooling. Therefore, thermal behavior resulting in large reductions in skin temperature is effective at alleviating thermal discomfort during exercise without affecting whole body heat loss. NEW & NOTEWORTHY This study aimed to determine the effectiveness of thermal behavior in maintaining thermal comfort during exercise by allowing subjects to voluntarily cool their torso and upper limbs with 2°C water throughout a light-intensity exercise protocol. We show that voluntary cooling of the upper body alleviates thermal discomfort while maintaining heat balance through convective rather than evaporative means of heat loss.

High environmental temperatures are associated with increased risk of acute kidney injury, which may be related to reductions in renal blood flow. The susceptibility of the kidneys may be increased because of heat stress-induced changes in renal vascular resistance (RVR) to sympathetic activation. We tested the hypotheses that, compared with normothermia, increases in RVR during the cold pressor test (CPT, a sympathoexcitatory maneuver) are attenuated during passive heating and exacerbated after cooling recovery. Twenty-four healthy adults (22 ± 2 yr; 12 women, 12 men) completed CPTs at normothermic baseline, after passive heating to a rise in core temperature of ~1.2°C, and after cooling recovery when core temperature returned to ~0.2°C above normothermic baseline. Blood velocity was measured by Doppler ultrasound in the distal segment of the right renal artery (Renal, n = 24 during thermal stress, n = 12 during CPTs) or the middle portion of a segmental artery (Segmental, n = 12). RVR was calculated as mean arterial pressure divided by renal or segmental blood velocity. RVR increased at the end of CPT during normothermic baseline in both arteries (Renal: by 1.0 ± 1.0 mmHg·cm−1·s, Segmental: by 2.2 ± 1.2 mmHg·cm−1·s, P ≤ 0.03), and these increases were abolished with passive heating ( P ≥ 0.76). At the end of cooling recovery, RVR in both arteries to the CPT was restored to that of normothermic baseline ( P ≤ 0.17). These data show that increases in RVR to sympathetic activation during passive heating are attenuated and return to that of normothermic baseline after cooling recovery. NEW & NOTEWORTHY Our data indicate that increases in renal vascular resistance to the cold pressor test (i.e., sympathetic activation) are attenuated during passive heating, but at the end of cooling recovery this response returns to that of normothermic baseline. Importantly, hemodynamic responses were assessed in arteries going to (renal artery) and within (segmental artery) the kidney, which has not been previously examined in the same study during thermal and/or sympathetic stressors.

We tested the hypothesis that thermal behavior is greater during and after high- compared with moderate-intensity exercise. In a 27°C, 20% relative humidity environment, 20 participants (10 women, 10 men) cycled for 30 min at moderate [53% (SD 6) peak oxygen uptake (V̇o2peak) or high [78% (SD 6) V̇o2peak] intensity, followed by 120 min of recovery. Mean skin and core temperatures and mean skin wettedness were recorded continuously. Participants maintained thermally comfortable neck temperatures with a custom-made neck device. Neck device temperature provided an index of thermal behavior. The weighted average of mean skin and core temperatures and mean skin wettedness provided an indication of the afferent stimulus to thermally behave. Mean skin and core temperatures were greater at end-exercise in high intensity ( P < 0.01). Core temperature remained elevated in high intensity until 70 min of recovery ( P = 0.03). Mean skin wettedness and the afferent stimulus were greater at 10–20 min of exercise in high intensity ( P ≤ 0.03) and remained elevated until 60 min of recovery ( P < 0.01). Neck device temperature was lower during exercise in high versus moderate intensity ( P ≤ 0.02). There was a strong relation between the afferent stimulus and neck device temperature during exercise (high: R2 = 0.82, P < 0.01; moderate: R2 = 0.95, P < 0.01) and recovery (high: R2 = 0.97, P < 0.01; moderate: R2 = 0.93, P < 0.01). During exercise, slope ( P = 0.49) and y-intercept ( P = 0.91) did not differ between intensities. In contrast, slope was steeper ( P < 0.01) and y-intercept was higher ( P < 0.01) during recovery from high-intensity exercise. Thermal behavior is greater during high-intensity exercise because of the greater stimulus to behave. The withdrawal of thermal behavior is augmented after high-intensity exercise. NEW & NOTEWORTHY This is the first study to determine the effects of exercise intensity on thermal behavior. We show that exercise intensity does not independently modulate thermal behavior during exercise but is dependent on the magnitude of afferent stimuli. In contrast, the withdrawal of thermal behavior after high-intensity exercise is augmented. This may be a consequence of an attenuated perceptual response to afferent stimuli, which may be due to processes underlying postexercise hypoalgesia.

The purpose of this study was to test the hypothesis that consuming a soft drink (i.e., a high-fructose, caffeinated beverage) during and following exercise in the heat elevates biomarkers of acute kidney injury (AKI) in humans. Twelve healthy adults drank 2 liters of an assigned beverage during 4 h of exercise in the heat [35.1 (0.1)°C, 61 (5)% relative humidity] in counterbalanced soft drink and water trials, and ≥1 liter of the same beverage after leaving the laboratory. Stage 1 AKI (i.e., increased serum creatinine ≥0.30 mg/dl) was detected at postexercise in 75% of participants in the Soft Drink trial compared with 8% in Water trial ( P = 0.02). Furthermore, urinary neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of AKI, was higher during an overnight collection period after the Soft Drink trial compared with Water in both absolute concentration [6 (4) ng/dl vs. 5 (4) ng/dl, P < 0.04] and after correcting for urine flow rate [6 (7) (ng/dl)/(ml/min) vs. 4 (4) (ng/dl)/(ml/min), P = 0.03]. Changes in serum uric acid from preexercise were greater in the Soft Drink trial than the Water trial at postexercise ( P < 0.01) and 24 h ( P = 0.05). There were greater increases from preexercise in serum copeptin, a stable marker of vasopressin, at postexercise in the Soft Drink trial ( P < 0.02) than the Water trial. These findings indicate that consuming a soft drink during and following exercise in the heat induces AKI, likely via vasopressin-mediated mechanisms.

Arterial hypercapnia reduces renal perfusion. Beetroot juice (BRJ) increases nitric oxide bioavailability and may improve renal blood flow. We tested the hypothesis that acute consumption of BRJ attenuates both decreases in blood velocity and increases in vascular resistance in the renal and segmental arteries during acute hypercapnia. In fourteen healthy young adults, blood velocity and vascular resistance were measured with Doppler ultrasound in the renal and segmental arteries during five minutes of breathing a carbon dioxide gas mixture (CO2) before and three hours after consuming 500 mL of BRJ. There was no difference between pre- and post-BRJ consumption in the increase in the partial pressure of end-tidal CO2 during CO2 breathing (pre: +4 ± 1 mmHg, post: +4 ± 2 mmHg, p = 0.4281). Segmental artery blood velocity decreased during CO2 breathing in both pre- (by −1.8 ± 1.9 cm/s, p = 0.0193) and post-BRJ (by −2.1 ± 1.9 cm/s, p = 0.0079), but there were no differences between pre- and post-consumption (p = 0.7633). Segmental artery vascular resistance increased from room air baseline during CO2 at pre-BRJ consumption (by 0.4 ± 0.4 mmHg/cm/s, p = 0.0153) but not post-BRJ (p = 0.1336), with no differences between pre- and post-consumption (p = 0.7407). These findings indicate that BRJ consumption does not attenuate reductions in renal perfusion during acute mild hypercapnia in healthy young adults.

The kidneys' integrative responses to heat stress aid thermoregulation, cardiovascular control, and water and electrolyte regulation. Recent evidence suggests the kidneys are at increased risk of pathological events during heat stress, namely acute kidney injury (AKI), and that this risk is compounded by dehydration and exercise. This heat stress related AKI is believed to contribute to the epidemic of chronic kidney disease (CKD) occurring in occupational settings. It is estimated that AKI and CKD affect upwards of 45 million individuals in the global workforce. Water and electrolyte disturbances and AKI, both of which are representative of kidney-related pathology, are the two leading causes of hospitalizations during heat waves in older adults. Structural and physiological alterations in aging kidneys likely contribute to this increased risk. With this background, this comprehensive narrative review will provide the first aggregation of research into the integrative physiological response of the kidneys to heat stress. While the focus of this review is on the human kidneys, we will utilize both human and animal data to describe these responses to passive and exercise heat stress, and how they are altered with heat acclimation. Additionally, we will discuss recent studies that indicate an increased risk of AKI due to exercise in the heat. Lastly, we will introduce the emerging public health crisis of older adults during extreme heat events and how the aging kidneys may be more susceptible to injury during heat stress.

This study tested the hypothesis that females rely on thermal behavior to a greater extent during and after exercise, relative to males.In a 24°C ± 1°C; (45% ± 10% RH) environment, 10 males (M) and 10 females (F) (22 ± 2 yr) cycled for 60 min (metabolic heat production: M, 117 ± 18 W·m; F, 129 ± 21 W·m), followed by 60-min recovery. Mean skin and core temperatures, skin blood flow and local sweat rates were measured continually. Subjects controlled the temperature of their dorsal neck to perceived thermal comfort using a custom-made device. Neck device temperature provided an index of thermal behavior and mean body temperature provided an index of the stimulus for thermal behavior. Data were analyzed for total area under the curve for exercise and recovery time points. To further isolate the effect of exercise on thermal behavior during recovery, data were also analyzed the minute mean body temperature returned to preexercise levels within a subject.There were no sex differences in metabolic heat production (P = 0.71) or body temperatures (P ≥ 0.10) during exercise. Area under the curve for neck device temperature during exercise was greater for F (-98.4°C·min ± 33.6°C·min vs -64.5°C·min ± 47.8°C·min, P = 0.04), but did not differ during recovery (F, 86.8°C·min ± 37.8°C·min; M, 65.6°C·min ± 35.9°C·min; P = 0.11). In M, mean skin (P = 0.90), core (P = 0.70) and neck device (P = 0.99) temperatures had recovered by the time that mean body temperature had returned to preexercise levels. However, in F, neck device temperature (P = 0.04) was reduced while core temperature remained elevated (P0.01).Females use thermal behavior during exercise to a greater extent than M. During recovery, thermal behavior may compensate for elevated core temperatures in F despite mean body temperatures returning to preexercise levels.

We tested the hypothesis that the motivation to behaviorally thermoregulate in humans is dependent on the magnitude of changes in mean skin temperature. Ten healthy subjects (22 ± 3 y, 5 females) underwent 60 min of seated rest in a 32±1 °C or 42±1 °C environment (20% relative humidity). Trials were completed in a counterbalanced order. The motivation to behaviorally thermoregulate was measured using an operant behavior task on a fixed ratio schedule, in which subjects received thermal reinforcement after clicking a button 100 times. The reinforcer was 30 s of cooling on the dorsal aspect of the neck. The motivation to behave was defined as the cumulative number of button clicks over time and behavioral thermoregulation was defined as the change in neck skin temperature. Mean skin temperature was higher throughout the 42 °C versus the 32 °C trial (at 60 min: 36.3±0.5 °C vs. 34.5±0.5 °C, P

We tested the hypothesis that thermal behavior during the exercise recovery compensates for elevated core temperatures despite autonomic thermoeffector withdrawal. In a thermoneutral environment, 6 females and 6 males (22 ± 1 y) cycled for 60 min (225 ± 46 W metabolic heat production), followed by 60 min passive recovery. Mean skin and core temperatures, skin blood flow, and local sweat rate were measured continually. Subjects controlled the temperature of their dorsal neck to perceived thermal comfort using a custom-made neck device. Neck device temperature provided an index of thermal behavior. Mean body temperature, calculated as the average of mean skin and core temperatures, provided an index of the stimulus for thermal behavior. To isolate the independent effect of exercise on thermal behavior during recovery, data were analyzed post-exercise the exact minute mean body temperature recovered to pre-exercise levels within a subject. Mean body temperature returned to pre-exercise levels 28 ± 20 min into recovery (Pre: 33.5 ± 0.2, Post: 33.5 ± 0.2 °C, P = 0.20), at which point, mean skin temperature had recovered (Pre: 29.6 ± 0.4, Post: 29.5 ± 0.5 °C, P = 0.20) and core temperature (Pre: 37.3 ± 0.2, Post: 37.5 ± 0.3 °C, P = 0.01) remained elevated. Post-exercise, skin blood flow (Pre: 59 ± 78, Post: 26 ± 25 PU, P = 0.10) and local sweat rate (Pre: 0.05 ± 0.25, Post: 0.13 ± 0.14 mg/cm2 min−1, P = 0.09) returned to pre-exercise levels, while neck device temperature was depressed (Pre: 27.4 ± 1.1, Post: 21.6 ± 7.4 °C, P = 0.03). These findings suggest that thermal behavior compensates for autonomic thermoeffector withdrawal in the presence of elevated core temperatures post-exercise.

New Findings What is the central question of the study? Is central chemosensitivity blunted during thermoneutral head out water immersion in healthy humans? What is the main finding and its importance? Central chemosensitivity is augmented during thermoneutral head out water immersion in healthy men and women. Thus, we suggest that the central chemoreceptors do not contribute CO2 retention during head out water immersion. Abstract Carbon dioxide (CO2) retention occurs during water immersion. Therefore, we tested the hypothesis that central chemosensitivity to hypercapnia is blunted during two hours of thermoneutral head out water immersion (HOWI) in healthy young adults. Twenty-six participants (age: 22 ± 2 years, BMI: 24 ± 3 kg/m2, 14 women) participated in two experimental visits: a HOWI visit (HOWI) and a dry time-control visit (Control). Central chemosensitivity was assessed via a rebreathing test at baseline, 10 minutes, 60 minutes, 90 minutes, 120 minutes, and post HOWI and Control. End tidal CO2 tension (PETCO2), minute ventilation, blood pressure, and heart rate were recorded continuously. PETCO2 increased from baseline throughout HOWI (peak increase at 120 minutes: 2 ± 2 mmHg; p

We tested the hypotheses that older adults with cardiovascular co-morbidities will demonstrate greater changes in body temperature and exaggerated changes in blood pressure before initiating thermal behavior. We studied twelve healthy younger adults (Younger, 25 ± 4 y) and six older adults (‘At Risk’, 67 ± 4 y) taking prescription medications for at least two of the following conditions: hypertension, type II diabetes, hypercholesterolemia. Subjects underwent a 90-min test in which they voluntarily moved between cool (18.1 ± 1.8°C, RH: 29 ± 5%) and warm (40.2 ± 0.3°C, RH: 20 ± 0%) rooms when they felt ‘too cool’ (C→W) or ‘too warm’ (W→C). Mean skin and intestinal temperatures and blood pressure were measured. Data were analyzed as a change from pretest baseline. Changes in mean skin temperature were not different between groups at C→W (Younger: +0.2 ± 0.8°C, ‘At Risk’: +0.7 ± 1.8°C, P = 0.51) or W→C (Younger: +2.7 ± 0.6°C, ‘At Risk’: +2.9 ± 1.9°C, P = 0.53). Changes in intestinal temperature were not different at C→W (Younger: 0.0 ± 0.1°C, ‘At Risk’: +0.1 ± 0.2, P = 0.11), but differed at W→C (-0.1 ± 0.2°C vs. +0.1 ± 0.3°C, P = 0.02). Systolic pressure at C→W increased (Younger: +10 ± 9 mmHg, ‘At Risk’: +24 ± 17 mmHg) and at W→C decreased (Younger: −4 ± 13 mmHg, ‘At Risk’: -23 ± 19 mmHg) to a greater extent in ‘At Risk’ (P ≤ 0.05). Differences were also apparent for diastolic pressure at C→W (Younger: −2 ± 4 mmHg, ‘At Risk’: +17 ± 23 mmHg, P < 0.01), but not at W→C (Younger Y: +4 ± 13 mmHg, ‘At Risk’: −1 ± 6 mmHg, P = 0.29). Despite little evidence for differential control of thermal behavior, the initiation of behavior in ‘at risk’ older adults is preceded by exaggerated blood pressure responses.

Occupational heat stress increases the risk of acute kidney injury (AKI) and kidney disease. This study tested the hypothesis that attenuating the magnitude of hyperthermia (i.e., increase in core temperature) and/or dehydration during prolonged physical work in the heat attenuates increases in AKI biomarkers. Thirteen healthy adults (3 women, 23 ± 2 yr) exercised for 2 h in a 39.7 ± 0.6°C, 32 ± 3% relative-humidity environmental chamber. In four trials, subjects received water to remain euhydrated ( Water), continuous upper-body cooling ( Cooling), a combination of both ( Water + Cooling), or no intervention ( Control). The magnitude of hyperthermia (increased core temperature of 1.9 ± 0.3°C; P < 0.01) and dehydration (percent loss of body mass of −2.4 ± 0.5%; P < 0.01) were greatest in the Control group. There were greater increases in the urinary biomarkers of AKI in the Control trial: albumin (increase of 13 ± 11 μg/mL; P ≤ 0.05 compared with other trials), neutrophil gelatinase-associated lipocalin (NGAL) (increase of 16 ± 14 ng/dL, P ≤ 0.05 compared with Cooling and Water + Cooling groups), and insulin-like growth factor-binding protein 7 (IGFBP7) (increase of 227 ± 190 ng/mL; P ≤ 0.05 compared with other trials). Increases in IGFBP7 in the Control trial persisted after correcting for urine production/concentration. There were no differences in the AKI biomarker tissue inhibitor of metalloproteinase 2 (TIMP-2) between trials ( P ≥ 0.11). Our findings indicate that the risk of AKI is highest with greater magnitudes of hyperthermia and dehydration during physical work in the heat. Additionally, the differential findings between IGFBP7 (preferentially secreted in proximal tubules) and TIMP-2 (distal tubules) suggest the proximal tubules as the location of potential renal injury. NEW & NOTEWORTHY We demonstrate that the risk for acute kidney injury (AKI) is higher in humans with greater magnitudes of hyperthermia and dehydration during physical work in the heat and that alleviating the hyperthermia and/or limiting dehydration equally reduce the risk of AKI. The biomarker panel employed in this study suggests the proximal tubules as the location of potential renal injury.

KEY POINTS Skin wetness occurring secondary to the build-up of sweat on the skin provokes thermal discomfort, the precursor to engaging in cool-seeking behaviour. Associative evidence indicates that skin wetness stimulates cool-seeking behaviour to a greater extent than increases in core and mean skin temperatures. The independent contribution of skin wetness to cool-seeking behaviour during heat stress has never been established. We demonstrate that skin wetness augments cool-seeking behaviour during passive heat stress independently of differential increases in skin temperature and core temperature. We also identify that perceptions of skin wetness were not elevated despite increases in actual skin wetness. These data support the proposition that afferent signalling from skin wetness enhances the desire to engage in cool-seeking behaviour during passive heat stress. ABSTRACT This study tested the hypothesis that elevations in skin wetness augments cool-seeking behaviour during passive heat stress. Twelve subjects (6 females, age: 24 ± 2 y) donned a water-perfused suit circulating 34 °C water and completed two trials resting supine in a 28.5 ± 0.4 °C environment. The trials involved a 20 min baseline period (26 ± 3% relative humidity (RH)), 60 min while ambient humidity was maintained at 26±3% RH (LOW) or increased to 67 ± 5% RH (HIGH), followed by 60 min passive heat stress (HS) where the water temperature in the suit was incrementally increased to 50 °C. Subjects were able to seek cooling when their neck was thermally uncomfortable by pressing a button. Each button press initiated 30 s of -20 °C fluid perfusing through a custom-made device secured against the skin on the dorsal neck. Mean skin (Tskin ) and core (Tcore ) temperatures, mean skin wetness (Wskin ) and neck device temperature (Tdevice ) were measured continuously. Cool-seeking behaviour was determined from total time receiving cooling (TTcool ) and cumulative button presses. Tskin and Tcore increased during HS (P

An epidemic of chronic kidney disease (CKD) is occurring in laborers who undertake physical work in hot conditions. Rodent data indicate that heat exposure causes kidney injury, and when this injury is regularly repeated it can elicit CKD. Studies in humans demonstrate that a single bout of exercise in the heat increases biomarkers of acute kidney injury (AKI). Elevations in AKI biomarkers in this context likely reflect an increased susceptibility of the kidneys to AKI. Data largely derived from animal models indicate that the mechanism(s) by which exercise in the heat may increase the risk of AKI is multifactorial. For instance, heat-related reductions in renal blood flow may provoke heterogenous intrarenal blood flow. This can promote localized ischemia, hypoxemia and ATP depletion in renal tubular cells, which could be exacerbated by increased sodium reabsorption. Heightened fructokinase pathway activity likely exacerbates ATP depletion occurring secondary to intrarenal fructose production and hyperuricemia. Collectively, these responses can promote inflammation and oxidative stress, thereby increasing the risk of AKI. Equivalent mechanistic evidence in humans is lacking. Such an understanding could inform the development of countermeasures to safeguard the renal health of laborers who regularly engage in physical work in hot environments.

We tested the hypothesis that cool-seeking behavior during heat exposure is attenuated when physical effort is required. Twelve healthy adults (mean(SD), 24(4) years, four women) underwent three experimental trials during two hours of exposure to 41(1) °C, 20(0)% relative humidity in which subjects undertook intermittent exercise alternating between seated rest and cycling exercise at ~4 metabolic equivalents every 15 min. In all trials, subjects wore a water perfused suit top. In the control trial (Control), no water perfused the suit. In the other trials, subjects were freely able to perfuse 2.1(0.2) °C water through the suit. In one cooling trial, subjects received two minutes of cooling by pressing a button (Button). The other cooling trial permitted cooling by engaging in isometric handgrip exercise at 15% of maximal grip strength (Handgrip), with cooling maintained throughout the duration the required force was produced or until two minutes elapsed. In both Button and Handgrip, a one-minute washout proceeded cooling. Core temperature increased over time in all trials (P

What is the central question of this study? Do increases in metabolic heat production and sweat rate precede the initiation of thermoregulatory behaviour in resting humans exposed to cool and warm environments? What is the main finding and its importance? Thermoregulatory behaviour at rest in cool and warm environments is preceded by changes in vasomotor tone in glabrous and non-glabrous skin, but not by acute increases in metabolic heat production or sweat rate. These findings suggest that sweating and shivering are not obligatory for thermal behaviour to be initiated in humans. We tested the hypothesis that acute increases in metabolic heat production and sweating precede the initiation of thermoregulatory behaviour in resting humans exposed to cool and warm environments. Twelve healthy young subjects passively moved between 17 and 40°C rooms when they felt 'too cool' (C→W) or 'too warm' (W→C). Skin and internal (intestinal) temperatures, metabolic heat production, local sweat rate (forearm and chest) and cutaneous vascular conductance (CVC; forearm and fingertip) were measured continually. Compared with pretest baseline (31.8 ± 0.3°C), skin temperature was higher at C→W (32.0 ± 0.7°C; P = 0.01) and W→C (34.5 ± 0.5°C; P