Plasma epinephrine and norepinephrine responses to extreme heat exposures in young and older adults.

Hyperthermia is known as a hyperadrenergic state, yet there is a lack of data on the sympathetic responses to ambient heat stress in humans. Therefore, we investigated the plasma epinephrine and norepinephrine concentrations of healthy young and older adults exposed to 3 h of very hot and dry, as well as hot and humid, heat, both with accompanying activities of daily living. We hypothesized that older adults, compared with young adults, would have augmented increases in epinephrine and norepinephrine concentrations secondary to increased thermal strain. Young (n = 20) and older (n = 18) participants underwent two 3-h heat exposures on different days: very hot and dry [47°C and 15% relative humidity (RH)] and hot and humid (41°C and 40% RH). To mimic heat generation comparable to activities of daily living, participants performed seven 5-min bouts of light cycling (approximately 3 METS) dispersed throughout the heat exposure. We measured plasma concentrations of epinephrine and norepinephrine at baseline, end, and 2-h postheat exposure. There was a group-wide increase in epinephrine from baseline to the end of the heat exposure (Δ19 ± 27 pg/mL; P < 0.001) in the hot and humid condition, but not in the very hot and dry condition (Δ6 ± 19 pg/mL; P = 0.10). There were group-wide decreases in norepinephrine concentrations from baseline to the end of the heat exposure in both the very hot and dry (Δ-131 ± 169 pg/mL; P < 0.001) and the hot and humid (Δ-138 ± 157 pg/mL; P < 0.001) conditions, with both returning to near baseline at 2-h postexposure. These data suggest that ambient heating with accompanying bouts of light intermittent exercise may lead to decreases in circulating concentrations of norepinephrine.NEW & NOTEWORTHY Herein we present plasma epinephrine and norepinephrine concentrations to 3 h of very hot and dry, as well as hot and humid, heat exposures with accompanying activities of daily living in young and older participants. We found 1) increased plasma concentrations of epinephrine in young and older adults following the hot and humid, but not the very hot and dry exposures and 2) decreased concentrations of norepinephrine in both groups following exposure to both conditions.

Low-dose sufentanil does not affect tolerance to LBNP-induced central hypovolemia or blood pressure responses during the cold pressor test.

Hemorrhage is a leading cause of death in the pre-hospital setting. Since pain often accompanies a hemorrhagic insult, the administered pain medication must not interfere with critical autonomic regulation of arterial blood pressure and vital organ perfusion. The purpose of this study was to test two unique hypotheses: a) sublingual sufentanil (Dsuvia) impairs tolerance to progressive central hypovolemia, and b) sublingual sufentanil attenuates pain sensation and the accompanying cardiovascular responses to a noxious stimulus. Twenty-nine adults participated in this double-blinded, randomized, crossover, placebo-controlled trial. Following sublingual administration of sufentanil (30 µg) or placebo, participants completed a progressive lower-body negative pressure (LBNP) challenge to tolerance, followed by a cold pressor test (CPT) after LBNP recovery. Addressing the first aim, tolerance to LBNP was not different between trials (p = 0.495). Decreases in systolic blood pressure from baseline to the end of LBNP also did not differ between trials (time: p<0.001, trial p=0.477, interaction p=0.587). Finally, increases in heart rate from baseline to the end of LBNP did not differ between trials (time: p < 0.001, trial p= p=0.626, interaction p = 0.424). Addressing the second aim, sufentanil attenuated perceived pain (p < 0.001) in response to the CPT, though the magnitude of the change in mean blood pressure during the CPT (p = 0.078) was not different between trials. These data demonstrate that sublingual sufentanil does not impair tolerance to progressive central hypovolemia. Additionally, sublingual sufentanil attenuates perceived pain, but not the accompanying mean blood pressure responses to the CPT.

Comparing the Effects of Low-Dose Ketamine, Fentanyl, and Morphine on Hemorrhagic Tolerance and Analgesia in Humans.

Hemorrhage is a leading cause of preventable battlefield and civilian trauma deaths. Ketamine, fentanyl, and morphine are recommended analgesics for use in the prehospital (i.e., field) setting to reduce pain. However, it is unknown whether any of these analgesics reduce hemorrhagic tolerance in humans. We tested the hypothesis that fentanyl (75 µg) and morphine (5 mg), but not ketamine (20 mg), would reduce tolerance to simulated hemorrhage in conscious humans. Each of the three analgesics was evaluated independently among different cohorts of healthy adults in a randomized, crossover (within drug/placebo comparison), placebo-controlled fashion using doses derived from the Tactical Combat Casualty Care Guidelines for Medical Personnel. One minute after an intravenous infusion of the analgesic or placebo (saline), we employed a pre-syncopal limited progressive lower-body negative pressure (LBNP) protocol to determine hemorrhagic tolerance. Hemorrhagic tolerance was quantified as a cumulative stress index (CSI), which is the sum of products of the LBNP and the duration (e.g., [40 mmHg x 3 min] + [50 mmHg x 3 min] …). Compared with ketamine (p = 0.002 post hoc result) and fentanyl (p = 0.02 post hoc result), morphine reduced the CSI (ketamine (n = 30): 99 [73-139], fentanyl (n = 28): 95 [68-130], morphine (n = 30): 62 [35-85]; values expressed as a % of the respective placebo trial's CSI; median [IQR]; Kruskal-Wallis test p = 0.002). Morphine-induced reductions in tolerance to central hypovolemia were not well explained by a prediction model including biological sex, body mass, and age (R2=0.05, p = 0.74). These experimental data demonstrate that morphine reduces tolerance to simulated hemorrhage while fentanyl and ketamine do not affect tolerance. Thus, these laboratory-based data, captured via simulated hemorrhage, suggest that morphine should not be used for a hemorrhaging individual in the prehospital setting.

Low-dose morphine reduces pain perception and blood pressure, but not muscle sympathetic outflow, responses during the cold pressor test.

Our knowledge about how low-dose (analgesic) morphine affects autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low-dose morphine affects human autonomic cardiovascular responses during painful stimuli in conscious humans. Therefore, we tested the hypothesis that low-dose morphine reduces perceived pain and subsequent sympathetic and cardiovascular responses in humans during an experimental noxious stimulus. Twenty-nine participants (14 females/15 males; 29 ± 6 yr; 26 ± 4 kg·m-2, means ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed a cold pressor test (CPT; hand in ∼0.4°C ice bath for 2 min) before and ∼35 min after drug/placebo administration (5 mg iv morphine or saline). We compared pain perception (100 mm visual analog scale), muscle sympathetic nerve activity (MSNA; microneurography; 14 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) between trials (at both pre- and postdrug/placebo time points) using paired, two-tailed t tests. Before drug/placebo infusion, perceived pain (P = 0.92), ΔMSNA burst frequency (n = 14, P = 0.21), and Δmean BP (P = 0.39) during the CPT were not different between trials. After the drug/placebo infusion, morphine versus placebo attenuated perceived pain (morphine: 43 ± 20 vs. placebo: 57 ± 24 mm, P < 0.001) and Δmean BP (morphine: 10 ± 7 vs. placebo: 13 ± 8 mmHg, P = 0.003), but not ΔMSNA burst frequency (morphine: 10 ± 11 vs. placebo: 13 ± 11 bursts·min-1, P = 0.12), during the CPT. Reductions in pain perception and Δmean BP were only weakly related (r = 0.34, P = 0.07; postmorphine CPT minus postplacebo CPT). These data provide valuable information regarding how low-dose morphine affects autonomic cardiovascular responses during an experimental painful stimulus.NEW & NOTEWORTHY In this randomized, crossover, placebo-controlled trial, we found that low-dose morphine administration reduced pain perception and blood pressure responses during the cold pressor test via attenuated increases in heart rate and cardiac output. We also determined that muscle sympathetic outflow responses during the cold pressor test seem to be unaffected by low-dose morphine administration. Finally, our exploratory analysis suggests that biological sex does not influence morphine-induced antinociception in healthy adults.

Low-dose morphine reduces tolerance to central hypovolemia in healthy adults without affecting muscle sympathetic outflow.

Hemorrhage is a leading cause of preventable battlefield and civilian trauma deaths. Low-dose (i.e., an analgesic dose) morphine is recommended for use in the prehospital (i.e., field) setting. Morphine administration reduces hemorrhagic tolerance in rodents. However, it is unknown whether morphine impairs autonomic cardiovascular regulation and consequently reduces hemorrhagic tolerance in humans. Thus, the purpose of this study was to test the hypothesis that low-dose morphine reduces hemorrhagic tolerance in conscious humans. Thirty adults (15 women/15 men; 29 ± 6 yr; 26 ± 4 kg·m-2, means ± SD) completed this randomized, crossover, double-blinded, placebo-controlled trial. One minute after intravenous administration of morphine (5 mg) or placebo (saline), we used a presyncopal limited progressive lower-body negative pressure (LBNP) protocol to determine hemorrhagic tolerance. Hemorrhagic tolerance was quantified as a cumulative stress index (mmHg·min), which was compared between trials using a Wilcoxon matched-pairs signed-rank test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat blood pressure (photoplethysmography) during the LBNP test using mixed-effects analyses [time (LBNP stage) × trial]. Median LBNP tolerance was lower during morphine trials (placebo: 692 [473-997] vs. morphine: 385 [251-728] mmHg·min, P < 0.001, CI: -394 to -128). Systolic blood pressure was 8 mmHg lower during moderate central hypovolemia during morphine trials (post hoc P = 0.02; time: P < 0.001, trial: P = 0.13, interaction: P = 0.006). MSNA burst frequency responses were not different between trials (time: P < 0.001, trial: P = 0.80, interaction: P = 0.51). These data demonstrate that low-dose morphine reduces hemorrhagic tolerance in conscious humans. Thus, morphine is not an ideal analgesic for a hemorrhaging individual in the prehospital setting.NEW & NOTEWORTHY In this randomized, crossover, placebo-controlled trial, we found that tolerance to simulated hemorrhage was lower after low-dose morphine administration. Such reductions in hemorrhagic tolerance were observed without differences in MSNA burst frequency responses between morphine and placebo trials. These data, the first to be obtained in conscious humans, demonstrate that low-dose morphine reduces hemorrhagic tolerance. Thus, morphine is not an ideal analgesic for a hemorrhaging individual in the prehospital setting.

Quantifying the impact of heat on human physical work capacity; part IV: interactions between work duration and heat stress severity.

High workplace temperatures negatively impact physical work capacity (PWC). Although PWC loss models with heat based on 1-h exposures are available, it is unclear if further adjustments are required to accommodate repeated work/rest cycles over the course of a full work shift. Therefore, we examined the impact of heat stress exposure on human PWC during a simulated work shift consisting of six 1-h work-rest cycles. Nine healthy males completed six 50-min work bouts, separated by 10-min rest intervals and an extended lunch break, on four separate occasions: once in a cool environment (15 °C/50% RH) and in three different air temperature and relative humidity combinations (moderate, 35 °C/50% RH; hot, 40 °C/50% RH; and very hot, 40 °C/70%). To mimic moderate to heavy workload, work was performed on a treadmill at a fixed heart rate of 130 beats·min-1. During each work bout, PWC was quantified as the kilojoules expended above resting levels. Over the shift, work output per cycle decreased, even in the cool climate, with the biggest decrement after the lunch break and meal consumption. Expressing PWC relative to that achieved in the cool environment for the same work duration, there was an additional 5(± 4)%, 7(± 6)%, and 16(± 7)% decrease in PWC when work was performed across a full work shift for the moderate, hot, and very hot condition respectively, compared with 1-h projections. Empirical models to predict PWC based on the level of heat stress (Wet-Bulb Globe Temperature, Universal Thermal Climate Index, Psychrometric Wet-Bulb Temperature, Humidex, and Heat Index) and the number of work cycles performed are presented.

Quantifying the impact of heat on human physical work capacity; part II: the observed interaction of air velocity with temperature, humidity, sweat rate, and clothing is not captured by most heat stress indices.

Increasing air movement can alleviate or exacerbate occupational heat strain, but the impact is not well defined across a wide range of hot environments, with different clothing levels. Therefore, we combined a large empirical study with a physical model of human heat transfer to determine the climates where increased air movement (with electric fans) provides effective body cooling. The model allowed us to generate practical advice using a high-resolution matrix of temperature and humidity. The empirical study involved a total of 300 1-h work trials in a variety of environments (35, 40, 45, and 50 °C, with 20 up to 80% relative humidity) with and without simulated wind (3.5 vs 0.2 m∙s-1), and wearing either minimal clothing or a full body work coverall. Our data provides compelling evidence that the impact of fans is strongly determined by air temperature and humidity. When air temperature is ≥ 35 °C, fans are ineffective and potentially harmful when relative humidity is below 50%. Our simulated data also show the climates where high wind/fans are beneficial or harmful, considering heat acclimation, age, and wind speed. Using unified weather indices, the impact of air movement is well captured by the universal thermal climate index, but not by wet-bulb globe temperature and aspirated wet-bulb temperature. Overall, the data from this study can inform new guidance for major public and occupational health agencies, potentially maintaining health and productivity in a warming climate.

Quantifying the impact of heat on human physical work capacity; part III: the impact of solar radiation varies with air temperature, humidity, and clothing coverage.

Heat stress decreases human physical work capacity (PWC), but the extent to which solar radiation (SOLAR) compounds this response is not well understood. This study empirically quantified how SOLAR impacts PWC in the heat, considering wide, but controlled, variations in air temperature, humidity, and clothing coverage. We also provide correction equations so PWC can be quantified outdoors using heat stress indices that do not ordinarily account for SOLAR (including the Heat Stress Index, Humidex, and Wet-Bulb Temperature). Fourteen young adult males (7 donning a work coverall, 7 with shorts and trainers) walked for 1 h at a fixed heart rate of 130 beats∙min-1, in seven combinations of air temperature (25 to 45°C) and relative humidity (20 or 80%), with and without SOLAR (800 W/m2 from solar lamps). Cumulative energy expenditure in the heat, relative to the work achieved in a cool reference condition, was used to determine PWC%. Skin temperature was the primary determinant of PWC in the heat. In dry climates with exposed skin (0.3 Clo), SOLAR caused PWC to decrease exponentially with rising air temperature, whereas work coveralls (0.9 Clo) negated this effect. In humid conditions, the SOLAR-induced reduction in PWC was consistent and linear across all levels of air temperature and clothing conditions. Wet-Bulb Globe Temperature and the Universal Thermal Climate Index represented SOLAR correctly and did not require a correction factor. For the Heat Stress Index, Humidex, and Wet-Bulb Temperature, correction factors are provided enabling forecasting of heat effects on work productivity.

An advanced empirical model for quantifying the impact of heat and climate change on human physical work capacity.

Occupational heat stress directly hampers physical work capacity (PWC), with large economic consequences for industries and regions vulnerable to global warming. Accurately quantifying PWC is essential for forecasting impacts of different climate change scenarios, but the current state of knowledge is limited, leading to potential underestimations in mild heat, and overestimations in extreme heat. We therefore developed advanced empirical equations for PWC based on 338 work sessions in climatic chambers (low air movement, no solar radiation) spanning mild to extreme heat stress. Equations for PWC are available based on air temperature and humidity, for a suite of heat stress assessment metrics, and mean skin temperature. Our models are highly sensitive to mild heat and to our knowledge are the first to include empirical data across the full range of warm and hot environments possible with future climate change across the world. Using wet bulb globe temperature (WBGT) as an example, we noted 10% reductions in PWC at mild heat stress (WBGT = 18°C) and reductions of 78% in the most extreme conditions (WBGT = 40°C). Of the different heat stress indices available, the heat index was the best predictor of group level PWC (R2 = 0.96) but can only be applied in shaded conditions. The skin temperature, but not internal/core temperature, was a strong predictor of PWC (R2 = 0.88), thermal sensation (R2 = 0.84), and thermal comfort (R2 = 0.73). The models presented apply to occupational workloads and can be used in climate projection models to predict economic and social consequences of climate change.

Sustainable solutions to mitigate occupational heat strain - an umbrella review of physiological effects and global health perspectives.

BACKGROUND: Climate change is set to exacerbate occupational heat strain, the combined effect of environmental and internal heat stress on the body, threatening human health and wellbeing. Therefore, identifying effective, affordable, feasible and sustainable solutions to mitigate the negative effects on worker health and productivity, is an increasingly urgent need. OBJECTIVES: To systematically identify and evaluate methods that mitigate occupational heat strain in order to provide scientific-based guidance for practitioners. METHODS: An umbrella review was conducted in biomedical databases employing the following eligibility criteria: 1) ambient temperatures > 28 °C or hypohydrated participants, 2) healthy adults, 3) reported psychophysiological (thermal comfort, heart rate or core temperature) and/or performance (physical or cognitive) outcomes, 4) written in English, and 5) published before November 6, 2019. A second search for original research articles was performed to identify interventions of relevance but lacking systematic reviews. All identified interventions were independently evaluated by all co-authors on four point scales for effectiveness, cost, feasibility and environmental impact. RESULTS: Following screening, 36 systematic reviews fulfilled the inclusion criteria. The most effective solutions at mitigating occupational heat strain were wearing specialized cooling garments, (physiological) heat acclimation, improving aerobic fitness, cold water immersion, and applying ventilation. Although air-conditioning and cooling garments in ideal settings provide best scores for effectiveness, the limited applicability in certain industrial settings, high economic cost and high environmental impact are drawbacks for these solutions. However, (physiological) acclimatization, planned breaks, shading and optimized clothing properties are attractive alternative solutions when economic and ecological sustainability aspects are included in the overall evaluation. DISCUSSION: Choosing the most effective solution or combinations of methods to mitigate occupational heat strain will be scenario-specific. However, this paper provides a framework for integrating effectiveness, cost, feasibility (indoors and outdoor) and ecologic sustainability to provide occupational health and safety professionals with evidence-based guidelines.

Kidney Function Biomarkers During Extreme Heat Exposure in Young and Older Adults.

This study investigates the effects of extreme heat exposure on kidney function using plasma-based biomarkers in young and older adults.

Acute acetaminophen (paracetamol) ingestion improves time to exhaustion during exercise in the heat.

Acetaminophen (paracetamol) is a commonly used over-the-counter analgesic and antipyretic and has previously been shown to improve exercise performance through a reduction in perceived pain. This study sought to establish whether its antipyretic action may also improve exercise capacity in the heat by moderating the increase in core temperature. On separate days, 11 recreationally active participants completed two experimental time-to-exhaustion trials on a cycle ergometer in hot conditions (30°C, 50% relative humidity) after ingesting a placebo control or an oral dose of acetaminophen in a randomized, double-blind design. Following acetaminophen ingestion, participants cycled for a significantly longer period of time (acetaminophen, 23 ± 15 min versus placebo, 19 ± 13 min; P = 0.005; 95% confidence interval = 90-379 s), and this was accompanied by significantly lower core (-0.15°C), skin (-0.47°C) and body temperatures (0.19°C; P < 0.05). In the acetaminophen condition, participants also reported significantly lower ratings of thermal sensation (-0.39; P = 0.015), but no significant change in heart rate was observed (P > 0.05). This is the first study to demonstrate that an acute dose of acetaminophen can improve cycling capacity in hot conditions, and that this may be due to the observed reduction in core, skin and body temperature and the subjective perception of thermal comfort. These findings suggest that acetaminophen may reduce the thermoregulatory strain elicited from exercise, thus improving time to exhaustion.

The influence of acetaminophen on repeated sprint cycling performance.

INTRODUCTION: The aim of this study was to investigate the effect of acetaminophen on repeated sprint cycling performance. METHODS: Nine recreationally active male participants completed a graded exercise test, a familiarisation set of Wingate Anaerobic Tests (WAnTs) and two experimental sets of WAnTs (8 × 30 s sprints, 2 min active rest intervals). In the experimental WAnTs, participants ingested either 1.5 g acetaminophen or a placebo in a double-blind, randomised, crossover design. During the WAnT trials, participants provided ratings of perceived pain 20 s into each sprint. Mean and peak power output and heart rate were recorded immediately following each sprint, and percentage decrement in mean power output was subsequently calculated. RESULTS: Participants cycled at a significantly greater mean power output over the course of 8 WAnTs (p < 0.05) following the ingestion of acetaminophen (391 ± 74 vs. 372 ± 90 W), due to a significantly greater mean power output during sprints 6, 7 and 8 (p < 0.05). Percentage decrements in mean power output were also significantly reduced (p < 0.05) following acetaminophen ingestion (17 ± 14 vs. 24 ± 17 %). No significant differences in peak power output, perceived pain or heart rate were observed between conditions. CONCLUSION: Acetaminophen may have improved performance through the reduction of pain for a given work rate, thereby enabling participants to exercise closer to a true physiological limit. These results suggest that exercise may be regulated by pain perception, and that an increased pain tolerance can improve exercise performance.

Comparing the efficacy of different climate indices for prediction of labor loss, body temperatures, and thermal perception in a wide variety of warm and hot climates.

The purpose of this study was to investigate which climate/heat indices perform best in predicting heat-induced loss of physical work capacity (PWCloss). Integrating data from earlier studies, data from 982 exposures (75 conditions) exercising at a fixed cardiovascular load of 130 beats·min-1, in varying temperatures (15-50°C), humidities (20-80%), solar radiation (0-800 W·m-2), wind (0.2-3.5 m·s-1), and two clothing levels, were used to model the predictive power of ambient temperature, universal thermal climate index (UTCI), wet bulb globe temperature (WBGT), modified physiologically equivalent temperature (mPET), heat index, apparent temperature (AT), and wet bulb temperature (Twb) for the calculation of PWCloss, skin temperature (Tskin) and core-to-skin temperature gradient, and thermal perception (thermal sensation vote, TSV) in the heat. R2, RMSE, and Akaike information criterion were used indicating model performance. Indices not including wind/radiation in their calculation (Ta, heat index, AT, and Twb) struggled to provide consistent predictions across variables. For PWCloss and TSV, UTCI and WBGT had the highest predictive power. For Tskin, and core-to-skin temperature gradient, the physiological models UTCI and mPET worked best in seminude conditions, but clothed, AT, WBGT, and UTCI worked best. For all index predictions, Ta, vapor pressure, and Twb were shown to be the worst heat strain predictors. Although UTCI and WBGT had similar model performance using the full dataset, WBGT did not work appropriately in windy, hot-dry, conditions where WBGT predicted lower strain due to wind, whereas the empirical data, UTCI and mPET indicated that wind in fact increased the overall level of thermal strain. The findings of the current study highlight the advantages of using a physiological model-based index like UTCI when evaluating heat stress in dynamic thermal environments.NEW & NOTEWORTHY There is an urgent need to determine the optimal heat stress metric when forecasting the impact of heat stress on human performance, physiological stress, and perception. We analyzed a wealth of laboratory data, simulating heart rate (HR)-paced work with wide variations in air temperature, humidity, wind speed, solar radiation, and clothing. We conclude that the universal thermal climate index (UTCI) [followed by wet-bulb globe temperature (WBGT)] is the optimal heat index to reliably predict reductions in performance, and elevations in physiological and perceptual stress.

Compensatory reserve index during central hypovolemia and volume loading in healthy young and older hyperthermic adults: A pilot study.

The compensatory reserve index (CRI), derived from machine learning algorithms from peripherally obtained photoplethysmography signals, provides a non-invasive assessment of cardiovascular stability, that may be useful clinically. Briefly, the CRI device provides a value between 0 and 1, with 1 reflecting full compensable capabilities and 0 reflecting little to no compensable capabilities. However, the CRI algorithm was developed in younger to middle aged adults, such that it is unknown if older age modulates CRI responses to cardiovascular challenges. In young and older subjects, we compared CRI responses to normothermic and hyperthermic progressive lower body negative pressure (LBNP), and volume loading with saline infusion. Eleven younger (20-36 years) and 10 older (61-75 years) healthy participants underwent (1) graded normothermic LBNP up to 30 mmHg, (2) graded hyperthermic (1.5°C increase in blood temperature) LBNP up to 30 mmHg, and (3) infusion of 15 mL/kg saline (volume loading) with hyperthermia maintained. CRI was obtained throughout each procedure. CRI at 30 mmHg LBNP was 0.18 and 0.24 units greater in the older group during normothermic and hyperthermic LBNP, respectively. However, CRI was not different between age groups at any other LBNP stage, nor did CRI change with volume loading regardless of age. In response to passive hyperthermia alone, regression analyses showed that heart rate was the strongest predictor of CRI. Blood temperature, rate pressure product, and stroke volume were also predictive of CRI but to a lesser extent. In conclusion, age attenuates the reduction in CRI during progressive normothermic and hyperthermic LBNP, but only at 30 mmHg. Second, the CRI was unchanged during volume loading in all subjects. Future studies should determine whether the age differences in CRI reflect age differences in LBNP tolerance.

Sex Differences in Sympathetic Responses to Lower-Body Negative Pressure.

INTRODUCTION: Trauma-induced hemorrhage is a leading cause of death in prehospital settings. Experimental data demonstrate that females have a lower tolerance to simulated hemorrhage (i.e., central hypovolemia). However, the mechanism(s) underpinning these responses are unknown. Therefore, this study aimed to compare autonomic cardiovascular responses during central hypovolemia between the sexes. We hypothesized that females would have a lower tolerance and smaller increase in muscle sympathetic nerve activity (MSNA) to simulated hemorrhage. METHODS: Data from 17 females and 19 males, aged 19-45 yr, were retrospectively analyzed. Participants completed a progressive lower-body negative pressure (LBNP) protocol to presyncope to simulate hemorrhagic tolerance with continuous measures of MSNA and beat-to-beat hemodynamic variables. We compared responses at baseline, at two LBNP stages (-40 and -50 mmHg), and at immediately before presyncope. In addition, we compared responses at relative percentages (33%, 66%, and 100%) of hemorrhagic tolerance, calculated via the cumulative stress index (i.e., the sum of the product of time and pressure at each LBNP stage). RESULTS: Females had lower tolerance to central hypovolemia (female: 561 ± 309 vs male: 894 ± 304 min·mmHg [time·LBNP]; P = 0.003). At LBNP -40 and -50 mmHg, females had lower diastolic blood pressures (main effect of sex: P = 0.010). For the relative LBNP analysis, females exhibited lower MSNA burst frequency (main effect of sex: P = 0.016) accompanied by a lower total vascular conductance (sex: P = 0.028; main effect of sex). CONCLUSIONS: Females have a lower tolerance to central hypovolemia, which was accompanied by lower diastolic blood pressure at -40 and -50 mmHg LBNP. Notably, females had attenuated MSNA responses when assessed as relative LBNP tolerance time.

Exercise and Heat Stress in Well-Healed Burn Survivors: Effects of Cooling Modalities on Thermal and Perceptual Responses.

PURPOSE: Burn injuries that require grafting impair thermoregulation, which may dissuade individuals with such injuries from being physically active. We tested the hypothesis that cooling modalities attenuate core temperature elevations and perceptions of heat stress during physical activity in the heat among adults with well-healed burn injuries. METHODS: Adults with no burn injuries (non-burned), 20-40% body surface area burn injuries (moderate burn), and > 40% body surface area burn injuries (large burn) performed 1 hour of moderate intensity exercise (2.5 ± 0.2 mph and 2% grade) on four different occasions in two environmental conditions (30 °C & 39 °C, 40% relative humidity). Within each environmental condition, we applied one of the following cooling modalities, random assigned, for each visit: no cooling (control), fan at 4 m/s (fan), water spray every 5 min (water spray; scaled to burn area size), or a combination of water spray + fan. RESULTS: In 30 °C, perceptual strain index (PeSI) was reduced in the non-burned and moderate burn groups with water spray + fan, whereas PeSI was reduced with all cooling modalities in the large burn group. The cooling modalities did not affect core temperature responses. In the 39 °C environment, water spray and water spray + fan attenuated the elevation in core temperature (p ≤ 0.007) only in the large burn group. In the moderate burn group, PeSI was decreased with water spray + fan (p = 0.017). In the large burn group, both water spray alone and water spray + fan (p ≤ 0.041) lowered PeSI. CONCLUSIONS: For both environments across burn groups, the applied cooling modalities were generally more effective at reducing indices of perceptual strain relative to indices of thermal strain (e.g., core temperature).

Evidence for Chronotropic Incompetence in Well-healed Burn Survivors.

Due to various pathophysiological responses associated with a severe burn injury, we hypothesized that burn survivors exhibit chronotropic incompetence. To test this hypothesis, a graded peak oxygen consumption (V̇O2peak) test was performed in 94 adults (34 nonburned, 31 burn survivors with 14-35% body surface area grafted, and 29 burn survivors with >35% body surface area grafted). The threshold of 35% body surface area grafted was determined by receiver operating characteristic (ROC) curve analysis. Peak exercise heart rates (HRmax) were compared against age-predicted HRmax within each group. The proportion of individuals not meeting their age-predicted HRmax (within 5 b/min) were compared between groups. Age-predicted HRmax was not different from measured HRmax in the nonburned and moderate burn groups (P = .09 and .22, respectively). However, measured HRmax was 10 ± 6 b/min lower than the age-predicted HRmax in those with a large burn injury (P < .001). While 56 and 65% of individuals in the nonburned and moderate burn group achieved a measured HRmax within 5 b/min or greater of age-predicted HRmax, only 21% of those in the large burn group met this criterion (P < .001). These data provide preliminary evidence of chronotropic incompetence in individuals with severe burn injury covering >35% body surface area.

Aging Increases Enterocyte Damage during a 3-Hour Exposure to Very Hot and Dry Heat: A Preliminary Study.

Profound heat stress can damage the gastrointestinal barrier, leading to microbial translocation from the gut and subsequent systemic inflammation. Despite the greater vulnerability of older people to heat wave-related morbidity and mortality, it is unknown if age modulates gastrointestinal barrier damage and inflammation during heat stress. Therefore, the aim of this study was to determine if aging impacted enterocyte damage and systemic inflammatory responses to a 3-h exposure to very hot and dry (47 °C, 15% humidity) heat with accompanying activities of daily living (intermittent activity at 3 METS). Data from 16 young (age 21 to 39 years) and 16 older (age 65 to 76 years) humans were used to address this aim. In each group, log-transformed plasma concentrations of intestinal fatty acid binding protein (I-FABPlog), interleukin-8 (IL-8log), and tissue factor (TFlog) were assessed as indices of enterocyte damage, systemic inflammation, and blood coagulation, respectively, before and after the 3-h heat exposure. In the younger cohort, I-FABPlog concentration did not increase from pre to post heat exposure (p = 0.264, d = 0.20), although it was elevated in the older group (p = 0.014, d = 0.67). The magnitude of the increase in I-FABPlog was greater in the older participants (p = 0.084, d = 0.55). Across all participants, there was no correlation between the change in core temperature and the change in IFABPlog. There was no change in IL-8log in the younger group (p = 0.193, d = 0.23) following heat exposure, but we observed a decrease in IL-8log in the older group (p = 0.047, d = 0.48). TFlog decreased in the younger group (p = 0.071, d = 0.41), but did not change in the older group (p = 0.193, d = 0.15). Our data indicate that I-FABPlog concentration (an index of enterocyte damage) is increased in older humans during a 3-h extreme heat exposure. Future studies should determine whether this marker reflects increased gastrointestinal barrier permeability in older individuals during heat exposure.

Key Exercise Concepts in the Rehabilitation from Severe Burns.

This article presents information on the benefits of exercise in counteracting the detrimental effects of bed rest, and/or severe burns. Exercise is key for maintaining physical function, lean body mass, metabolic recovery, and psychosocial health after major burn injuries. The details of an exercise training program conducted in severely burned persons are presented, as well as information on the importance of proper regulation of body temperature during exercise or physical activity. The sections on exercise and thermoregulation are followed by a section on the role of exercise in scarring and contractures. Finally, gaps in the current knowledge of exercise, thermoregulation, and contractures are presented.