Search

The use of acute carbon monoxide inhalation (COi) and hot water immersion (HWI) are of growing interest as interventions to stimulate erythropoietin (EPO) production. However, whether EPO production is further augmented when combining these stressors and whether there are sex differences in this response are poorly understood. Therefore, we measured circulating EPO concentration in response to acute COi and HWI independently and in combination and determined whether the responses were altered by sex. Participants completed three study visits—COi, HWI, and combined COi and HWI—separated by 1 week in a randomized, balanced, crossover design. Renal blood velocity was measured during all interventions, and carboxyhaemoglobin was measured during and after COi. Serum samples were analysed every hour for 6 h post‐intervention for EPO concentration. HWI decreased renal blood velocity (46.2 cm/s to 36.2 cm/s) (P < 0.0001), and COi increased carboxyhaemoglobin (1.5%–12.8%) (P < 0.0001) without changing renal blood velocity (46.4–45.2 cm/s) (P = 0.4456). All three interventions increased peak EPO concentration from baseline (COi: 6.02–9.74 mIU/mL; HWI: 6.80–11.10 mIU/mL; COi + HWI: 6.71–10.91 mIU/mL) (P = 0.0048) and to the same extent (P = 0.3505). On average, females increased EPO while males did not in response to COi (females: 6.17 mIU/mL; males: 1.27 mIU/mL) (P = 0.0010), HWI (females: 6.47 mIU/mL; males: 2.14 mIU/mL) (P = 0.0104), and COi and HWI (females: 6.65 mIU/mL; males: 1.76 mIU/mL) (P = 0.0256). These data emphasize that combining these interventions does not augment EPO secretion and that these interventions may work better in females. What is the central question of the study?Do acute heat stress and carbon monoxide inhalation alone and in combination increase erythropoietin, and are there sex differences in erythropoietin?What is the main finding and its importance?All interventions increased erythropoietin, but combining the two interventions did not further augment erythropoietin. While erythropoietin increased in females in response to all interventions, there was greater erythropoietin variability in males and therefore, on average, males did not increase erythropoietin. This suggests that combining heat and hypoxic stressors does not further augment erythropoietin concentrations but these interventions may have greater efficacy in females. [ABSTRACT FROM AUTHOR]

Occupational heat stress increases the risk of acute kidney injury (AKI). This study presents a secondary analysis to generate novel hypotheses for future studies by investigating the diagnostic accuracy of thermal, hydration, and heart rate assessments in discriminating positive AKI risk following physical work in the heat in unacclimatized individuals. Unacclimatized participants (n = 13, 3 women, age: ∼23 years) completed four trials involving 2 h of exercise in a 39.7 ± 0.6 °C, 32 ± 3% relative humidity environment that differed by experimental manipulation of hyperthermia (i.e., cooling intervention) and dehydration (i.e., water drinking). Diagnostic accuracy was assessed via receiver operating characteristic curve analysis. Positive AKI risk was identified when the product of concentrations insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinase-2 [IGFBP7∙TIMP-2] exceeded 0.3 (ng∙mL−1)2∙1000−1. Peak absolute core temperature had the acceptable discriminatory ability (AUC = 0.71, p = 0.009), but a relatively large variance (AUC 95% CI: 0.57–0.86). Mean body temperature, urine specific gravity, urine osmolality, peak heart rate, and the peak percent of both maximum heart rate and heart rate reserve had poor discrimination (AUC = 0.66–0.69, p ≤ 0.051). Mean skin temperature, percent change in body mass and plasma volume, and serum sodium and osmolality had no discrimination (p ≥ 0.072). A peak increase in mean skin temperature of >4.7 °C had a positive likelihood ratio of 11.0 which suggests clinical significance. These data suggest that the absolute value of peak core temperature and the increase in mean skin temperature may be valuable to pursue in future studies as a biomarker for AKI risk in unacclimatized workers. [ABSTRACT FROM AUTHOR]

Men are likely at greater risk for heat-induced acute kidney injury compared with women, possibly due to differences in vascular control. We tested the hypothesis that the renal vasoconstrictor and vasodilator responses will be greater in younger women compared with men during passive heat stress. Twenty-five healthy adults [12 women (early follicular phase) and 13 men] completed two experimental visits, heat stress or normothermic time-control, assigned in a block-randomized crossover design. During heat stress, participants wore a water-perfused suit perfused with 50°C water. Core temperature was increased by ∼0.8°C in the first hour before commencing a 2-min cold pressor test (CPT). Core temperature remained clamped and at 1-h post-CPT, subjects ingested a whey protein shake (1.2 g of protein/kg body wt), and measurements were taken pre-, 75 min, and 150 min post-protein. Beat-to-beat blood pressure (Penaz method) was measured and segmental artery vascular resistance (VR, Doppler ultrasound) was calculated as segmental artery blood velocity ÷ mean arterial pressure. CPT-induced increases in segmental artery VR did not differ between trials (trial effect: P = 0.142) nor between men (heat stress: 1.5-±-1.0 mmHg/cm/s, normothermia: 1.4-±-1.0 mmHg/cm/s) and women (heat stress: 1.4-±-1.2 mmHg/cm/s, normothermia: 2.1-±-1.1 mmHg/cm/s) (group effect: P = 0.429). Reductions in segmental artery VR following oral protein loading did not differ between trials (trial effect: P = 0.080) nor between men (heat stress: −0.6-±-0.8 mmHg/cm/s, normothermia: −0.6-±-0.6 mmHg/cm/s) and women (heat stress: −0.5-±-0.5 mmHg/cm/s, normothermia: −1.1-±-0.6 mmHg/cm/s) (group effect: P = 0.204). Renal vasoconstrictor responses to the cold pressor test and vasodilator responses following an oral protein load during heat stress or normothermia do not differ between younger men and younger women in the early follicular phase of the menstrual cycle. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Wet bulb temperatures (Twet) during extreme heat events are commonly 31°C. Recent predictions indicate that Twet 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 Twet = 34°C compared with Twet = 31°C. Fifteen healthy men rested for 8 h in Twet = 31 (0)°C and Twet = 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 [þ26.9 (27.1) (ng/mL)²/ 1,000) compared with the 31°C [þ6.2 (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 [þ77.6 (47.5) ng/min] compared with the 31°C [þ16.2 (25.1) ng/min] trial (P < 0.01). Plasma IL-17a, an inflammatory marker, was elevated at 8 h in the 34°C [þ199.3 (90.0) fg/dL; P < 0.01] compared with the 31°C [þ9.0 (95.7) fg/dL] trial. Kidney injury risk is exacerbated during prolonged resting exposures to Twet experienced during future extreme heat events (34°C) compared with that experienced currently (31°C), likely because of oxidative stress and inflammatory processes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The purpose of this study was to test the hypothesis that consuming a soft drink (i.e., a highfructose, 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. [ABSTRACT FROM AUTHOR]

Keywords: altitude; brain blood flow; cerebral blood flow; cold stress; heat stress; hypoxia Most of these studies have not assessed CBF and CDO SB 2 sb as mechanisms underlying these changes in cognitive function with independent or combined exposures to cold stress and hypoxia. Importantly, they found that exposure to acute hypoxia during cold stress attenuates the hypocapnia-induced cerebral vasoconstriction and that altitude acclimatization exacerbates the reductions in CBF and CDO SB 2 sb during cold stress. Altitude, brain blood flow, cerebral blood flow, cold stress, heat stress, hypoxia. [Extracted from the article]

Purpose: We tested the hypothesis that elevations in biomarkers of acute kidney injury are influenced by the magnitude of hyperthermia and dehydration elicited by two common firefighter work durations. Methods: Twenty-nine healthy adults (10 females) wearing firefighter protective clothing completed two randomized trials where they walked at 4.8 km⋅h-1, 5% grade in a 38°C, 50% RH environment. In the short trial, subjects completed two 20-min exercise bouts. In the long trial (LONG), subjects completed three 20-min exercise bouts. Each exercise bout was separated by 10 min of standing rest in an ~20°C environment. Venous blood samples were obtained before and immediately after exercise, and after 1 h recovery. Dependent variables included changes in core temperature, body weight, plasma volume, serum creatinine, and plasma neutrophil gelatinase-associated lipocalin, a marker of renal tubule injury. Results: Changes in core temperature (+2.0°C ± 0.7°C vs +1.1 °C ± 0.4°C, P < 0.01), body weight (-0.9% ± 0.6% vs -0.5% ± 0.5%, P < 0.01), and plasma volume (-11% ± 5% vs -8% ± 6%, P < 0.01) during exercise were greater in LONG. Increases in creatinine were higher in LONG postexercise (0.18 ± 0.15 vs 0.08 ± 0.07 mg⋅dL-1, P < 0.01) and after recovery (0.21 ± 0.16 vs 0.14 ± 0.10 mg⋅dL-1, P < 0.01). Increases in neutrophil gelatinase-associated lipocalin were greater in LONG postexercise (27.0 ± 20.5 vs 12.7 ± 18.0 ng⋅mL-1, P = 0.01) and after recovery (16.9 ± 15.6 vs 1.5 ± 15.1 ng⋅mL-1, P = 0.02). Conclusions: Biomarkers of acute kidney injury are influenced by the magnitude of hyperthermia and hypovolemia elicited by exercise in the heat. [ABSTRACT FROM AUTHOR]

Although there are physiological and cognitive challenges to the brain during acute heat stress, current epidemiological evidence indicates that heat therapy reduces the risk of stroke, dementia, and Alzheimer's disease. Keywords: cerebral blood flow; cerebral vascular function; cerebrovascular reactivity; heat stress; intracranial pressure EN cerebral blood flow cerebral vascular function cerebrovascular reactivity heat stress intracranial pressure 2789 2790 2 06/05/21 20210601 NES 210601 There has been a surge of renewed interest in understanding how chronic, repetitive exposure to passive heating (i.e. heat therapy) can be used to elicit beneficial adaptations to improve human health. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

• Motivational conflict decreases warm-seeking behavior during cold exposure. • The effect of motivational conflict on cooling during heat exposure was unknown. • It was found that voluntary cooling is lower when physical effort is required. • These findings elucidate the control of cool-seeking behavior during heat events. 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 <0.01) and there were no differences between trials (P = 0.32). Mean skin temperature at the end of heat exposure was lowest in Button [34.2(1.5) °C] compared to Handgrip [35.6(0.8) °C, P = 0.03] and Control [36.9(0.7) °C, P <0.01]. The total number of behaviors [8(3) vs. 10(5), P = 0.04] and cumulative cooling time [850(323) vs. 1230(616) seconds, P = 0.02] were lower in Handgrip compared to Button. These data indicate that when physical effort is required, the incidence and duration of cooling behavior during heat exposure is attenuated compared to when behaving requires minimal physical effort. [ABSTRACT FROM AUTHOR]