Revisiting regional variation in the age-related reduction in sweat rate during passive heat stress.

Aging is associated with attenuated sweat gland function, which has been suggested to occur in a peripheral-to-central manner. However, evidence supporting this hypothesis remains equivocal. We revisited this hypothesis by evaluating the sweat rate across the limbs and trunk in young and older men during whole-body, passive heating. A water-perfused suit was used to raise and clamp esophageal temperature at 0.6°C (low-heat strain) and 1.2°C (moderate-heat strain) above baseline in 14 young (24 (SD 5) years) and 15 older (69 (4) years) men. Sweat rate was measured at multiple sites on the trunk (chest, abdomen) and limbs (biceps, forearm, quadriceps, calf) using ventilated capsules (3.8 cm2 ). Sweat rates, expressed as the average of 5 min of stable sweating at low- and moderate-heat strain, were compared between groups (young, older) and regions (trunk, limbs) within each level of heat strain using a linear mixed-effects model with nested intercepts (sites nested within region nested within participant). At low-heat strain, the age-related reduction in sweat rate (older-young values) was greater at the trunk (0.65 mg/cm2 /min [95% CI 0.44, 0.86]) compared to the limbs (0.42 mg/cm2 /min [0.22, 0.62]; interaction: p = 0.010). At moderate-heat strain, sweat rate was lower in older compared to young (main effect: p = 0.025), albeit that reduction did not differ between regions (interaction: p = 0.888). We conclude that, contrary to previous suggestions, the age-related decline in sweat rate was greater at the trunk compared to the limbs at low-heat strain, with no evidence of regional variation in that age-related decline at moderate-heat strain.

Effect of extracellular hyperosmolality during normothermia and hyperthermia on the autophagic response in peripheral blood mononuclear cells from young men.

Heat-stress-induced dehydration is associated with extracellular hyperosmolality. To counteract the associated stress, cells employ cytoprotective mechanisms, including autophagy; however, the autophagic response to hyperosmotic stress has yet to be evaluated in humans. Thus, we investigated autophagy and associated cellular stress pathways [the heat shock response (HSR), apoptosis, and the acute inflammatory response] to isosmotic and hyperosmotic conditions with and without hyperthermia in 12 young men (mean [SD]; 25 [5] yr). Participants received a 90-min intravenous infusion of either isosmotic (ISO; 0.9% NaCl; serum osmolality of 293 [4] mosmol/kgH2O) or hyperosmotic (HYP; 3.0% NaCl; 300 [6] mosmol/kgH2O) saline, followed by passive whole body heating using water perfused suit to increase esophageal temperature by ∼0.8°C. Peripheral blood mononuclear cells were harvested at baseline (preinfusion), postinfusion, and after heating, and changes in protein content were analyzed via Western blotting. Post infusion, the LC3-II/I ratio was higher in HYP compared with ISO infusion (P < 0.001), although no other protein changes were observed (all P > 0.050). Following passive heating, autophagy increased in HYP, as demonstrated by an increase in LC3-II from baseline (P = 0.004) and an elevated LC3-II/I ratio compared with ISO (P = 0.035), and a decrease in p62 when compared with the ISO condition (P = 0.019). This was accompanied by an elevation in cleaved caspase-3 following heating in the HYP condition (P < 0.010); however, the HSR and acute inflammatory response did not change under any condition (all P > 0.050). Taken together, our findings indicate that serum hyperosmolality induces autophagy and apoptotic signaling during mild hyperthermia with minimal autophagic activation during normothermia.NEW & NOTEWORTHY We demonstrate that a physiologically relevant increase in serum osmolality causes minimal activation of the autophagic response. However, the combined stressors of serum hyperosmolality and mild hyperthermia causes activation of both autophagy and apoptotic signaling. Thus, changes in osmotic homeostasis appear to influence the cell's cytoprotective ability during periods of heat stress, highlighting the importance of considering osmotic status when examining autophagic responses in vivo.

Effect of extracellular hyperosmolality on sweat rate during metaboreflex activation in passively heated young men.

Metaboreflex activation augments sweating during mild-to-moderate hyperthermia in euhydrated (isosmotic isovolemic) individuals. Recent work indicates that extracellular hyperosmolality may augment metaboreflex-mediated elevations in sympathetic nervous activity. Our primary objective was, therefore, to test the hypothesis that extracellular hyperosmolality would exacerbate metaboreflex-mediated increases in sweat rate. On two separate occasions, 12 young men [means (SD): 25 (5) yr] received a 90-min intravenous infusion of either 0.9% saline (isosmotic condition, ISO) or 3.0% saline (hyperosmotic condition, HYP), resulting in a postinfusion serum osmolality of 290 (3) and 301 (7) mosmol/kgH2O, respectively. A whole body water perfusion suit was then used to increase esophageal temperature by 0.8°C above resting. Participants then performed a metaboreflex activation protocol consisting of 90-s isometric handgrip exercise (40% of their predetermined maximum voluntary contraction), followed by 150 s of brachial occlusion (trapping produced metabolites within the limb). Metaboreflex-induced sweating was quantified as the change in global sweat rate (from preisometric handgrip exercise to brachial occlusion), estimated as the surface area-weighted average of local sweat rate on the abdomen, axilla, chest, bicep, quadriceps, and calf, measured using ventilated capsules (3.8 cm2). We also explored whether this response differed between body regions. The change in global sweat rate due to metaboreflex activation was significantly greater in HYP compared with ISO (0.03 mg/min/cm2 [95% confidence interval: 0.00, 0.06]; P = 0.047), but was not modulated by body region (site × condition interaction: P = 0.679). These findings indicate that extracellular hyperosmolality augments metaboreflex-induced increases in global sweat rate, with no evidence for region-specific differences.

Myths and methodologies: Reliability of forearm cutaneous vasodilatation measured using laser-Doppler flowmetry during whole-body passive heating.

Laser-Doppler flowmetry (LDF) is commonly used to assess cutaneous vasodilatation responses, but its reliability (i.e. consistency) during whole-body passive heating is unknown. We therefore assessed the reliability of LDF-derived indices of cutaneous vasodilatation during incremental whole-body heating. Fourteen young men (age: 24 (SD 5) years) completed three identical trials, each separated by 1 week. During each trial, a water-perfused suit was used to raise and clamp oesophageal temperature at 0.6°C (low-heat strain; LHS) and 1.2°C (moderate-heat strain; MHS) above baseline. LDF-derived skin blood flow (SkBF) was measured at three dorsal mid-forearm sites, with local skin temperature clamped at 34°C. Data were expressed as absolute cutaneous vascular conductance (CVCabs ; SkBF/mean arterial pressure) and normalised to maximal conductance (%CVCmax ) achieved via simultaneous local skin heating to 44°C and increasing oesophageal temperature to 1.8°C above baseline. Between-day reliability was characterised as measurement consistency across trials, while within-day reliability was characterised as measurement consistency across adjacent skin sites during each trial. Between- and within-day absolute reliability (coefficient of variation) generally improved with increasing heat strain, changing from poor (>25%) at baseline, poor-to-moderate (15-34%) at LHS, and moderate (10-25%) at MHS. Generally, these estimates were more consistent when expressed as %CVCmax . Conversely, relative reliability was mostly acceptable (intraclass correlation coefficient ≥0.70) during LHS and when data were expressed as CVCabs . These findings indicate that the consistency of LDF-derived CVC estimates during heat stress depends on the level of heat strain and method of data expression, which should be considered when designing and interpreting experiments.

Regional variation in the reliability of sweat rate measured via the ventilated capsule technique during passive heating.

The ventilated capsule technique is widely used to measure time-dependent changes in sweating in humans. However, evaluations of its reliability (consistency) have been restricted to the forearm, despite extensive regional heterogeneity in the sweating response. Given the importance of such information for experimental design, statistical analysis and interpretation, we determined the reliability of local sweat rate at nine sites during whole-body passive (resting) heating. On three separate occasions, a water-perfused suit was used to increase and clamp oesophageal temperature 0.6, 1.2 and 1.8°C above baseline in 14 young men [24 (SD 5) years of age], while sweat rate was measured at the forehead, chest, abdomen, biceps, forearm, hand, quadriceps, calf and foot using ventilated capsules (3.8 cm2 ). Absolute and relative reliability were determined via the coefficient of variation (CV) and intraclass correlation coefficient (ICC), respectively. At low heat strain (0.6°C), almost all sites had acceptable relative reliability (ICC ≥ 0.70) and moderate absolute reliability (CV < 25%). At moderate heat strain (1.2°C), only the abdomen, hand, quadriceps and foot had acceptable relative reliability, whereas the forehead, abdomen, forearm, hand and quadriceps had moderate absolute reliability. At high heat strain (1.8°C), relative reliability was acceptable at the abdomen, quadriceps, calf and foot, whereas the chest, abdomen, forearm, hand, quadriceps, calf and foot had moderate absolute reliability. Our findings indicate that the measurement site and level of heat strain impact the consistency of local sweat rate measured via the ventilated capsule technique, and we demonstrate the possible implications for research design and data interpretation.

Myths and methodologies: Reliability of non-invasive estimates of cardiac autonomic modulation during whole-body passive heating.

Observed individual variability in cardiac baroreflex sensitivity (cBRS) and heart rate variability (HRV) is extensive, especially during exposure to stressors such as heat. A large part of the observed variation may be related to the reliability (consistency) of the measurement. We therefore examined the test-retest reliability of cBRS and HRV measurements on three separate occasions in 14 young men (age: 24 (SD 5) years), at rest and during whole-body heating (water-perfused suit) to raise and clamp oesophageal temperature 0.6°C, 1.2°C and 1.8°C above baseline. Beat-to-beat measurements of RR interval and systolic blood pressure (BP) were obtained for deriving HRV (from RR), and cBRS calculated via (i) the spontaneous method, α coefficients and transfer function analysis at each level of heat strain, and (ii) during forced oscillations via squat-stand manoeuvres (0.1 Hz) before and after heating. Absolute values and changes in all cBRS estimates were variable but generally consistent with reductions in parasympathetic activity. cBRS estimates demonstrated poor absolute reliability (coefficient of variation ≥25%), but relative reliability (intraclass correlation coefficient; ICC) of some frequency estimates was acceptable (ICC ≥0.70) during low-heat strain (ICC: 0.56-0.74). After heating, forced oscillations in BP demonstrated more favourable responses than spontaneous oscillations (better reliability, lower minimum detectable change). Absolute reliability of HRV estimates were poor, but relative reliability estimates were often acceptable (≥0.70). Our findings illustrate how measurement consistency of cardiac autonomic modulation estimates are altered during heat stress, and we demonstrate the possible implications on research design and data interpretation.

Ageing attenuates the effect of extracellular hyperosmolality on whole-body heat exchange during exercise-heat stress.

KEY POINTS: In humans, hypohydration attenuates sweat secretion and attenuates whole-body heat loss, probably to mitigate further fluid losses and thereby support blood pressure regulation. Recently, however, we demonstrated that the hypohydration-mediated reduction in net whole-body heat exchange (evaporative heat loss - dry heat gain) was blunted in middle-aged compared to younger men during moderate exercise in dry heat; albeit, the underpinning mechanisms could not be determined. Here we evaluated the hypothesis that those findings stemmed from a diminished influence of extracellular hyperosmolality on net whole-body heat exchange in middle-aged-to-older compared to young men. Consistent with that hypothesis, extracellular hyperosmolality induced by an intravenous infusion of hypertonic saline (3% NaCl) reduced net heat exchange and augmented rectal temperature to a greater extent in the young compared to middle-aged-to-older men. Thus, age-related differences in the influence of hypohydration on thermoregulatory function appear to be due to blunted sensitivity to hyperosmolality with ageing. ABSTRACT: We recently demonstrated that sweating-induced hypohydration attenuated whole-body heat dissipation to a greater extent in young compared to middle-aged men during exercise-heat stress. Here, we evaluated whether this divergent response stemmed from an attenuated influence of extracellular hyperosmolality on heat exchange with ageing. To achieve this, ten young (mean (SD): 25 (5) years) and ten middle-aged-to-older (61 (5) years) men completed two trials involving a 90-min intravenous infusion of isosmotic saline (0.9% NaCl; ISO) or hyperosmotic saline (3.0% NaCl; HYP) followed by 60 min of cycling at a fixed metabolic heat production of 250 W/m2 (∼50% peak aerobic power) in dry heat (40°C, ∼17% relative humidity). Whole-body net heat exchange (evaporative heat loss - dry heat gain) was measured via direct calorimetry. Rectal temperature was monitored continuously. Heat exchange was attenuated in HYP compared to ISO in the young (233 (20) vs. 251 (17) W/m2 ; P = 0.002) but not older group (229 (16) vs. 227 (20) W/m2 ; P = 0.621). Further, heat exchange was lower in the middle-aged-to-older vs. young men in ISO (P = 0.034) but not in HYP (P = 0.623). Similarly, end-exercise rectal temperature was greater in HYP relative to ISO in the young (38.3 (0.4)°C vs. 37.9 (0.3)°C; P = 0.015) but not the middle-aged-to-older men (38.3 (0.3)°C vs. 38.2 (0.2)°C; P = 0.652). Compared to the young, rectal temperature was greater in the middle-aged-to-older during ISO (P = 0.035) whereas no between-group difference was observed in HYP (P = 0.746). Our findings indicate that ageing blunts the effect of extracellular hyperosmolality on thermoregulatory function during exercise-heat stress.

Heat Exchange in Young and Older Men during Constant- and Variable-Intensity Work.

PURPOSE: Current occupational heat stress guidelines rely on time-weighted averaging to quantify the metabolic demands of variable-intensity work. However, variable-intensity work may be associated with impairments in whole-body total heat loss (dry + evaporative heat loss), especially in older workers, which exacerbate heat strain relative to constant-intensity work eliciting the same time-weighted average metabolic rate. We, therefore, used direct calorimetry to evaluate whether variable-intensity work would cause decrements in the average rate of whole-body total heat loss that augment body heat storage and core temperature compared with constant-intensity work in young and older men. METHODS: Eight young (19-31 yr) and eight older (54-65 yr) men completed four trials involving 90 min of work (cycling) eliciting an average metabolic heat production of ~200 W·m in dry-heat (40°C, 20% relative humidity). One trial involved constant-intensity work (CON), whereas the others involved 10-min cycles of variable-intensity work: 5-min low-intensity and 5-min high-intensity (VAR 5:5), 6-min low-intensity and 4-min very high-intensity (VAR 6:4), and 7-min low- and 3-min very, very high-intensity (VAR 7:3). Metabolic heat production, total heat loss, body heat storage (heat production minus total heat loss), and core (rectal) temperature were measured throughout. RESULTS: When averaged over each 90-min work period, metabolic heat production, total heat loss, and heat storage were similar between groups and conditions (all P ≥ 0.152). Peak core temperature (average of final 10 min) was also similar between groups and conditions (both P ≥ 0.111). CONCLUSIONS: Whole-body total heat loss, heat storage, and core temperature were not significantly influenced by the partitioning of work intensity in young or older men, indicating that time-weighted averaging appears to be appropriate for quantifying the metabolic demands of variable-intensity work to assess occupational heat stress.