Burn size and environmental conditions modify thermoregulatory responses to exercise in burn survivors.

This project tested the hypothesis that burn survivors can perform mild/moderate-intensity exercise in temperate and hot environments without excessive elevations in core body temperature. Burn survivors with low (23 ± 5%TBSA; N = 11), moderate (40 ± 5%TBSA; N = 9), and high (60 ± 8%TBSA; N = 9) burn injuries performed 60 minutes of cycle ergometry exercise (72 ± 15 watts) in a 25°C and 23% relative humidity environment (ie, temperate) and in a 40°C and 21% relative humidity environment (ie, hot). Absolute gastrointestinal temperatures (TGI) and changes in TGI (ΔTGI) were obtained. Participants with an absolute TGI of >38.5°C and/or a ΔTGI of >1.5°C were categorized as being at risk for hyperthermia. For the temperate environment, exercise increased ΔTGI in all groups (low: 0.72 ± 0.21°C, moderate: 0.42 ± 0.22°C, and high: 0.77 ± 0.25°C; all P < .01 from pre-exercise baselines), resulting in similar absolute end-exercise TGI values (P = .19). Importantly, no participant was categorized as being at risk for hyperthermia, based upon the aforementioned criteria. For the hot environment, ΔTGI at the end of the exercise bout was greater for the high group when compared to the low group (P = .049). Notably, 33% of the moderate cohort and 56% of the high cohort reached or exceeded a core temperature of 38.5°C, while none in the low cohort exceeded this threshold. These data suggest that individuals with a substantial %TBSA burned can perform mild/moderate intensity exercise for 60 minutes in temperate environmental conditions without risk of excessive elevations in TGI. Conversely, the risk of excessive elevations in TGI during mild/moderate intensity exercise in a hot environment increases with the %TBSA burned.

Attrition of Well-Healed Burn Survivors to a 6-Month Community-Based Exercise Program: A Retrospective Evaluation.

The purpose of this study was to evaluate whether burn survivors have lower adherence compared to non-burned control individuals during a 6-month community-based exercise program. In burn survivors, we sought to answer if there was a relation between the size of the burn injury and dropout frequency. Fifty-two burn survivors and 15 non-burned controls (n = 67) were recruited for a 6-month community-based (ie, non-supervised), progressive, exercise training program. During the exercise program, 27% (ie, 4 of the 15 enrolled) of the non-burned individuals dropped out of the study, while 37% (ie, 19 of the 52) of the burn survivors dropped out from the study. There was no difference in the percentage of individuals who dropped out between groups (P = .552). There was no difference in size of the burn injury, expressed as percent body surface area burned (%BSA) between the burn survivors that dropped out versus those who completed the exercise regimen (P = .951). We did not observe a relation between %BSA burned and dropouts (log odds = -0.15-0.01(%BSA), B = -0.01, SE = 0.015, P = .541). There was no effect of %BSA burned on the probability of dropout [Exp (B) = 0.991, 95% CI (0.961, 1.020)] and there were no differences in the percentage of individuals who dropped out of the study based on %BSA burned (χ2(1) = 0.44, P = .51). These data demonstrate that burn survivors have similar exercise adherence relative to a non-burned group and the extent of a burn injury does not affect exercise program adherence.

Inhibiting regional sweat evaporation modifies the ventilatory response to exercise: interactions between core and skin temperature.

In humans, elevated body temperatures can markedly increase the ventilatory response to exercise. However, the impact of changing the effective body surface area (BSA) for sweat evaporation (BSAeff) on such responses is unclear. Ten healthy adults (9 males, 1 female) performed eight exercise trials cycling at 6 W/kg of metabolic heat production for 60 min. Four conditions were used where BSAeff corresponded to 100%, 80%, 60%, and 40% of BSA using vapor-impermeable material. Four trials (one at each BSAeff) were performed at 25°C air temperature, and four trials (one at each BSAeff) at 40°C air temperature, each with 20% humidity. The slope of the relation between minute ventilation and carbon dioxide elimination (V̇E/V̇co2 slope) assessed the ventilatory response. At 25°C, the V̇E/V̇co2 slope was elevated by 1.9 and 2.6 units when decreasing BSAeff from 100 to 80 and to 40% (P = 0.033 and 0.004, respectively). At 40°C, V̇E/V̇co2 slope was elevated by 3.3 and 4.7 units, when decreasing BSAeff from 100 to 60 and to 40% (P = 0.016 and P < 0.001, respectively). Linear regression analyses using group average data from each condition demonstrated that end-exercise mean body temperature (integration of core and mean skin temperature) was better associated with the end-exercise ventilatory response, compared with core temperature alone. Overall, we show that impeding regional sweat evaporation increases the ventilatory response to exercise in temperate and hot environmental conditions, and the effect is mediated primarily by increases in mean body temperature.NEW & NOTEWORTHY Exercise in the heat increases the slope of the relation between minute ventilation and carbon dioxide elimination (V̇E/V̇co2 slope) in young healthy adults. An indispensable role for skin temperature in modulating the ventilatory response to exercise is noted, contradicting common belief that internal/core temperature acts independently as a controller of ventilation during hyperthermia.

Six Months of Exercise Training Improves Ventilatory Responses during Exercise in Adults with Well-Healed Burn Injuries.

INTRODUCTION: Pulmonary function is lower after a severe burn injury, which could influence ventilatory responses during exercise. It is unclear whether exercise training improves pulmonary function or ventilatory responses during exercise in adults with well-healed burn injuries. Therefore, we tested the hypothesis that exercise training improves pulmonary function and ventilatory responses during exercise in adults with well-healed burn injuries. METHODS: Thirty-nine adults (28 with well-healed burn injuries and 11 non-burn-injured controls) completed 6 months of unsupervised, progressive exercise training including endurance, resistance, and high-intensity interval components. Before and after exercise training, we performed comprehensive pulmonary function testing and measured ventilatory responses during cycling exercise. We compared variables using two-way ANOVA (group-time; i.e., preexercise/postexercise training (repeated factor)). RESULTS: Exercise training did not increase percent predicted spirometry, lung diffusing capacity, or airway resistance measures (time: P ≥ 0.14 for all variables). However, exercise training reduced minute ventilation ( V̇E ; time: P ≤ 0.05 for 50 and 75 W) and the ventilatory equivalent for oxygen ( V̇E /V̇O 2 ; time: P < 0.001 for 75 W) during fixed-load exercise for both groups. The ventilatory equivalent for carbon dioxide ( V̇E /V̇CO 2 ) during exercise at 75 W was reduced after exercise training (time: P = 0.04). The percentage of age-predicted maximum heart rate at the ventilatory threshold was lower in adults with well-healed burn injuries before ( P = 0.002), but not after ( P = 0.22), exercise training. Lastly, exercise training increased V̇E and reduced V̇E /V̇O 2 during maximal exercise (time: P = 0.005 for both variables). CONCLUSIONS: These novel findings demonstrate that exercise training can improve ventilatory responses during exercise in adults with well-healed burn injuries.

Cardiac remodeling in well-healed burn survivors after 6 months of unsupervised progressive exercise training.

Aerobic exercise is important in the rehabilitation of individuals with prior burn injuries, but no studies have examined whether adult burn survivors demonstrate cardiac remodeling to long-term aerobic exercise training. In this study, we tested the hypothesis that 6 months of progressive exercise training improves cardiac magnetic resonance imaging-based measures of cardiac structure and function in well-healed burn survivors. Secondary analyses explored relations between burn surface area and changes in cardiac structure in the cohort of burn survivors. V̇o2peak assessments and cardiac magnetic resonance imaging were performed at baseline and following 6 months of progressive exercise training from 19 well-healed burn survivors and 10 nonburned control participants. V̇o2peak increased following 6 months of training in both groups (Control: Δ5.5 ± 5.8 mL/kg/min; Burn Survivors: Δ3.2 ± 3.6 mL/kg/min, main effect of training, P < 0.001). Left ventricle (LV) mass (Control: Δ1.7 ± 3.1 g/m2; Burn survivors: Δ1.8 ± 2.7 g/m2), stroke volume (Control: Δ5.8 ± 5.2 mL/m2; Burn Survivors: Δ2.8 ± 4.2 mL/m2), and ejection fraction (Control: Δ2.4 ± 4.0%; Burn Survivors: Δ2.2 ± 4.3%) similarly increased following 6 months of exercise training in both cohorts (main effect of training P < 0.05 for all indexes). LV end-diastolic volume increased in the control group (Δ6.5 ± 4.5 mL/m2) but not in the cohort of burn survivors (Δ1.9 ± 2.7 mL/m2, interaction, P = 0.040). Multiple linear regression analyses revealed that burn surface area had little to no effect on changes in ventricular mass or end-diastolic volumes in response to exercise training. Our findings provide initial evidence of physiological cardiac remodeling, which is not impacted by burn size, in response to exercise training in individuals with well-healed burn injuries.NEW & NOTEWORTHY Aerobic exercise is important in the rehabilitation of individuals with prior burn injuries, but no studies have examined whether adult burn survivors demonstrate cardiac remodeling to long-term aerobic exercise training. In this study, we tested the hypothesis that 6 months of progressive exercise training would improve cardiac magnetic resonance imaging-based measures of cardiac structure and function in well-healed burn survivors. Our findings highlight the ability of exercise training to modify cardiac structure and function in well-healed burn survivors and nonburned sedentary controls alike.

Altered cardiac ß1 responsiveness in hyperthermic older adults.

Compared with younger adults, passive heating induced increases in cardiac output are attenuated by ∼50% in older adults. This attenuated response may be associated with older individuals' inability to maintain stroke volume through ionotropic mechanisms and/or through altered chronotropic mechanisms. The purpose of this study was to identify the interactive effect of age and hyperthermia on cardiac responsiveness to dobutamine-induced cardiac stimulation. Eleven young (26 ± 4 yr) and 8 older (68 ± 5 yr) participants underwent a normothermic and a hyperthermic (baseline core temperature +1.2°C) trial on the same day. In both thermal conditions, after baseline measurements, intravenous dobutamine was administered for 12 min at 5 µg/kg/min, followed by 12 min at 15 µg/kg/min. Primary measurements included echocardiography-based assessments of cardiac function, gastrointestinal and skin temperatures, heart rate, and mean arterial pressure. Heart rate responses to dobutamine were similar between groups in both thermal conditions (P > 0.05). The peak systolic mitral annular velocity (S'), i.e., an index of left ventricular longitudinal systolic function, was similar between groups for both thermal conditions at baseline. While normothermic, the increase in S' between groups was similar with dobutamine administration. However, while hyperthermic, the increase in S' was attenuated in the older participants with dobutamine (P < 0.001). Healthy, older individuals show attenuated inotropic, but maintained chronotropic responsiveness to dobutamine administration during hyperthermia. These data suggest that older individuals have a reduced capacity to increase cardiomyocyte contractility, estimated by changes in S', via ß1-adrenergic mechanisms while hyperthermic.

Six months of unsupervised exercise training lowers blood pressure during moderate, but not vigorous, aerobic exercise in adults with well-healed burn injuries.

Exercise training reduces cardiovascular disease risk, partly due to arterial blood pressure (BP) lowering at rest and during fixed-load exercise. However, it is unclear whether exercise training can reduce BP at rest and during exercise in adults with well-healed burn injuries. Therefore, the purpose of this investigation was to test the hypothesis that 6 mo of unsupervised exercise training reduces BP at rest and during lower-body cycle ergometry in adults with well-healed burn injuries. Thirty-nine adults (28 with well-healed burn injuries and 11 controls) completed 6 mo of unsupervised, progressive exercise training including endurance, resistance, and high-intensity interval components. Before and after exercise training, we measured BP at rest, during fixed-load submaximal exercise (50 and 75 W), during fixed-intensity submaximal exercise (40% and 70% of V̇o2peak), and during maximal exercise on a lower-body cycle ergometer. We compared cardiovascular variables using two-way ANOVA (group × pre/postexercise training [repeated factor]). Adults with well-healed burn injuries had higher diastolic BP at rest (P = 0.04), which was unchanged by exercise training (P = 0.26). Exercise training reduced systolic, mean, and diastolic BP during fixed-load cycling exercise at 75 W in adults with well-healed burn injuries (P ≤ 0.03 for all), but not controls (P ≥ 0.67 for all). Exercise training also reduced mean and diastolic BP during exercise at 40% (P ≤ 0.02 for both), but not at 70% (P ≥ 0.18 for both), of V̇o2peak. These data suggest that a 6-mo unsupervised exercise training program lowers BP during moderate, but not vigorous, aerobic exercise in adults with well-healed burn injuries.NEW & NOTEWORTHY Adults with well-healed burn injuries have greater cardiovascular disease morbidity and all-cause mortality compared with nonburn-injured adults. We found that exercise training reduced blood pressure (BP) during fixed-load cycling at 75 W and during moderate, but not vigorous, intensity cycling exercise in adults with well-healed burn injuries. These data suggest that 6 mo of unsupervised exercise training provides some degree of cardioprotection by reducing BP responses during submaximal exercise in well-healed burn-injured adults.

Human temperature regulation under heat stress in health, disease, and injury.

The human body constantly exchanges heat with the environment. Temperature regulation is a homeostatic feedback control system that ensures deep body temperature is maintained within narrow limits despite wide variations in environmental conditions and activity-related elevations in metabolic heat production. Extensive research has been performed to study the physiological regulation of deep body temperature. This review focuses on healthy and disordered human temperature regulation during heat stress. Central to this discussion is the notion that various morphological features, intrinsic factors, diseases, and injuries independently and interactively influence deep body temperature during exercise and/or exposure to hot ambient temperatures. The first sections review fundamental aspects of the human heat stress response, including the biophysical principles governing heat balance and the autonomic control of heat loss thermoeffectors. Next, we discuss the effects of different intrinsic factors (morphology, heat adaptation, biological sex, and age), diseases (neurological, cardiovascular, metabolic, and genetic), and injuries (spinal cord injury, deep burns, and heat stroke), with emphasis on the mechanisms by which these factors enhance or disturb the regulation of deep body temperature during heat stress. We conclude with key unanswered questions in this field of research.

Adults with well-healed burn injuries have lower pulmonary function values decades after injury.

Sub-acute (e.g., inhalation injury) and/or acute insults sustained during a severe burn injury impairs pulmonary function. However, previous work has not fully characterized pulmonary function in adults with well-healed burn injuries decades after an injury. Therefore, we tested the hypothesis that adults with well-healed burn injuries have lower pulmonary function years after recovery. Our cohort of adults with well-healed burn-injuries (n = 41) had a lower forced expiratory volume in one second (Burn: 93 ± 16 vs. Control: 103 ± 10%predicted, mean ± SD; d = 0.60, p = 0.04), lower maximal voluntary ventilation (Burn: 84 [71-97] vs. Control: 105 [94-122] %predicted, median [IQR]; d = 0.84, p < 0.01), and a higher specific airway resistance (Burn: 235 ± 80 vs. Control: 179 ± 40%predicted, mean ± SD; d = 0.66, p = 0.02) than non-burned control participants (n = 12). No variables were meaningfully influenced by having a previous inhalation injury (d ≤ 0.44, p ≥ 0.19; 13 of 41 had an inhalation injury), the size of the body surface area burned (R2  ≤ 0.06, p ≥ 0.15; range of 15%-88% body surface area burned), or the time since the burn injury (R2  ≤ 0.04, p ≥ 0.22; range of 2-50 years post-injury). These data suggest that adults with well-healed burn injuries have lower pulmonary function decades after injury. Therefore, future research should examine rehabilitation strategies that could improve pulmonary function among adults with well-healed burn injuries.

Edward F. Adolph Distinguished Lecture. It's more than skin deep: thermoregulatory and cardiovascular consequences of severe burn injuries in humans.

Each year, within the United States, tens of thousands of individuals are hospitalized for burn-related injuries. The treatment of deep burns often involves skin grafts to accelerate healing and reduce the risk of infection. The grafting procedure results in a physical disruption between the injured and subsequently debrided host site and the skin graft placed on top of that site. Both neural and vascular connections must occur between the host site and the graft for neural modulation of skin blood flow to take place. Furthermore, evaporative cooling from such burn injured areas is effectively absent, leading to greatly impaired thermoregulatory responses in individuals with large portions of their body surface area burned. Hospitalization following a burn injury can last weeks to months, with cardiovascular and metabolic consequences of such injuries having the potential to adversely affect the burn survivor for years postdischarge. With that background, the objectives of this article are to discuss 1) our current understanding of the physiology and associated consequences of skin grafting, 2) the effects of skin grafts on efferent thermoregulatory responses and the associated consequences pertaining to whole body thermoregulation, 3) approaches that may reduce the risk of excessive hyperthermia in burn survivors, 4) the long-term cardiovascular consequences of burn injuries, and 5) the extent to which burn survivors can "normalize" otherwise compromised cardiovascular responses. Our primary objective is to guide the reader toward an understanding that severe burn injuries result in significant physiological consequences that can persist for years after the injury.

Thermoregulatory Responses with Size-matched Simulated Torso or Limb Skin Grafts.

PURPOSE: This study aimed to test the hypothesis that a simulated burn injury on the torso will be no more or less detrimental to core temperature control than on the limbs during uncompensable exercise-heat stress. METHODS: Nine nonburned individuals (7 men, 2 women) completed the protocol. On separate occasions, burn injuries of identical surface area (0.45 ± 0.08 m2 or 24.4% ± 4.4% of total body surface area) were simulated on the torso or the arms/legs using an absorbent, vapor-impermeable material that impedes sweat evaporation in those regions. Participants performed 60 min of treadmill walking at 5.3 km·h-1 and a 4.1% ± 0.8% grade, targeting 6 W·kg-1 of metabolic heat production in 40.1°C ± 0.2°C and 19.6% ± 0.6% relative humidity conditions. Rectal temperature, heart rate, and perceptual responses were measured. RESULTS: Rectal temperature increased to a similar extent with simulated injuries on the torso and limbs (condition-by-time interaction, P = 0.86), with a final rectal temperature 0.9°C ± 0.3°C above baseline in both conditions. No differences in heart rate, perceived exertion, or thermal sensation were observed between conditions (condition-by-time interactions, P ≥ 0.50). CONCLUSIONS: During uncompensable exercise-heat stress, sized-matched simulated burn injuries on the torso or limbs evoke comparable core temperature, heart rate, and perceptual responses, suggesting that the risk of exertional heat illness in such environmental conditions is independent of injury location.

Normobaric hypoxia does not alter the critical environmental limits for thermal balance during exercise-heat stress.

NEW FINDINGS: What is the central question of this study? Hypoxia reportedly does not impair thermoregulation during exercise in compensable heat stress conditions: does it have an impact on maximal heat dissipation and therefore the critical environmental limit for the physiological compensability of core temperature? What is the main finding and its importance? Although skin blood flow was higher in hypoxia, no differences in sweat rates or the critical environmental limit for the physiological compensability of core temperature - an indicator of maximal heat loss - were found compared to exercise in normoxia, indicating no influence of normobaric hypoxia on thermoregulatory capacity in warm conditions. ABSTRACT: Altered control of skin blood flow (SkBF) in hypoxia does not impair thermoregulation during exercise in compensable conditions, but its impact on maximal heat dissipation is unknown. This study therefore sought to determine whether maximum heat loss is altered by hypoxia during exercise in warm conditions. On separate days, eight males exercised for 90 min at a fixed heat production of ∼500 W in normoxia (NORM) or normobaric hypoxia (HYP, FIO2  = 0.13) in a 34°C environment. Ambient vapour pressure was maintained at 2.13 kPa for 45 min, after which it was raised 0.11 kPa every 7.5 min. The critical ambient vapour pressure at which oesophageal temperature inflected upward (Pcrit ) indicated that maximum heat dissipation had been reached. Neither local sweat rates on the upper arm, back and forehead (average NORM: 1.46 (0.15) vs. HYP: 1.41 (0.16) mg cm-2  min-1 ; P = 0.59) nor whole-body sweat losses (NORM: 1029 (137) g vs. HYP: 1025 (150) g; P = 0.95) were different between trials. Laser-Doppler flux values (LDF; arbitrary units), an index of SkBF, were not different between NORM and HYP on the forearm (P = 0.23) or back (P = 0.73); however, when normalized as a percentage of maximum, LDF values tended to be higher in HYP compared to NORM at the forearm (condition effect, P = 0.05) but not back (P = 0.19). Despite potentially greater SkBF in hypoxia, there was no difference in Pcrit between conditions (NORM: 3.67 (0.35) kPa; HYP: 3.46 (0.39) kPa; P = 0.22). These findings suggest that hypoxia does not independently alter thermoregulatory capacity during exercise in warm conditions.

Interaction of Exercise Intensity and Simulated Burn Injury Size on Thermoregulation.

PURPOSE: This study aimed to test the hypothesis that the elevation in internal body temperature during exercise in a hot environment is influenced by the combination of exercise intensity and BSA burned. METHODS: Ten healthy participants (8 males, 2 females; 32 ± 9 yr; 75.3 ± 11.7 kg) completed eight exercise trials on a cycle ergometer, each with different combinations of metabolic heat productions (low, 4 W·kg-1; moderate, 6 W·kg-1) and simulated BSA burn in a hot environmental chamber (39.9°C ± 0.3°C, 20.1% ± 1.5% RH). Burns were simulated by covering 0%, 20%, 40%, or 60% of participants' BSA with a highly absorbent, vapor-impermeable material. Gastrointestinal temperature (TGI) was recorded, with the primary analysis being the increase in TGI after 60 min of exercise. RESULTS: We identified an interaction effect for the increase in TGI (P < 0.01), suggesting TGI was influenced by both intensity and simulated burn BSA. Regardless of the percentage BSA burn simulated, the increase in TGI was similar across low-intensity trials (0.70°C ± 0.26°C, P > 0.11 for all). However, during moderate-intensity exercise, the increase in TGI was greater for the 60% (1.78°C ± 0.38°C, P < 0.01) and 40% BSA coverage trials (1.33°C ± 0.44°C, P = 0.04), relative to 0% (0.82°C ± 0.36°C). There were no differences in TGI responses between 0% and 20% trials. CONCLUSION: These data suggest that exercise intensity influences the relationship between burn injury size and thermoregulatory responses in a hot environment.

Low dose ketamine reduces pain perception and blood pressure, but not muscle sympathetic nerve activity, responses during a cold pressor test.

KEY POINTS: Low dose ketamine is a leading medication used to provide analgesia in pre-hospital and hospital settings. Low dose ketamine is increasingly used off-label to treat conditions such as depression. In animals, ketamine stimulates the sympathetic nervous system and increases blood pressure, but these physiological consequences have not been studied in conscious humans. Our data suggest that low dose ketamine administration blunts pain perception and reduces blood pressure, but not muscle sympathetic nerve activity burst frequency, responses during a cold pressor test in healthy humans. These mechanistic, physiological results inform risk-benefit analysis for clinicians administering low dose ketamine in humans. ABSTRACT: Low dose ketamine is an effective analgesic medication. However, our knowledge of the effects of ketamine on autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low dose ketamine influences autonomic cardiovascular responses during painful stimuli in humans. We tested the hypothesis that low dose ketamine blunts perceived pain, and blunts subsequent sympathetic and cardiovascular responses during an experimental noxious stimulus. Twenty-two adults (10F/12M; 27 ± 6 years; 26 ± 3 kg m-2 , mean ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed cold pressor tests (CPT; hand in ∼0.4°C ice bath for 2 min) pre- and 5 min post-drug administration (20 mg ketamine or saline). We compared pain perception (100 mm visual analogue scale), muscle sympathetic nerve activity (MSNA; microneurography, 12 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) during the pre- and post-drug CPTs separately using paired, two-tailed t tests. For the pre-drug CPT, perceived pain (P = 0.4378), MSNA burst frequency responses (P = 0.7375), and mean BP responses (P = 0.6457) were not different between trials. For the post-drug CPT, ketamine compared to placebo administration attenuated perceived pain (P < 0.0001) and mean BP responses (P = 0.0047), but did not attenuate MSNA burst frequency responses (P = 0.3662). Finally, during the post-drug CPT, there was a moderate relation between cardiac output and BP responses after placebo administration (r = 0.53, P = 0.0121), but this relation was effectively absent after ketamine administration (r = -0.12, P = 0.5885). These data suggest that low dose ketamine administration attenuates perceived pain and pressor, but not MSNA burst frequency, responses during a CPT.

Exercise Training Improves Microvascular Function in Burn Injury Survivors.

INTRODUCTION: Vasodilator function is impaired in individuals with well-healed burn injuries; however, therapeutic interventions that lessen or reverse this maladaptation are lacking. The purpose of this study was to test the hypothesis that a 6-month community-based exercise training program would increase microvascular dilator function in individuals with well-healed burn injuries, irrespective of the magnitude of the injured body surface area. Further, we hypothesize that macrovascular dilator function would remain unchanged posttraining. METHODS: Microvascular function (forearm reactive hyperemia), macrovascular function (brachial artery flow-mediated dilation), and the maximal vasodilatory response after ischemic handgrip exercise (an estimate of microvascular remodeling) were assessed before and after exercise training in nonburned control subjects (n = 11) and individuals with burn injuries covering a moderate body surface area (26% ± 7%; n = 13) and a high body surface area (59% ± 15%; n = 19). RESULTS: Peak vascular conductance and area under the curve during postocclusive reactive hyperemia increased from pretraining to posttraining in control and burn injury groups (both P < 0.05), the magnitude of which did not differ between groups (both P = 0.6). Likewise, the maximal vasodilatory response after ischemic handgrip exercise increased in all groups after exercise training (P < 0.05). Macrovascular dilator function did not differ across time or between groups (P = 0.8). CONCLUSIONS: These data suggest that a community-based exercise training program improves microvascular function in individuals with well-healed burn injuries, which may be due in part to vascular remodeling.

Low-dose ketamine affects blood pressure, but not muscle sympathetic nerve activity, during progressive central hypovolemia without altering tolerance.

KEY POINTS: Haemorrhage is the leading cause of battlefield and civilian trauma deaths. Given that a haemorrhagic injury on the battlefield is almost always associated with pain, it is paramount that the administered pain medication does not disrupt the physiological mechanisms that are beneficial in defending against the haemorrhagic insult. Current guidelines from the US Army's Committee on Tactical Combat Casualty Care (CoTCCC) for the selection of pain medications administered to a haemorrhaging soldier are based upon limited scientific evidence, with the clear majority of supporting studies being conducted on anaesthetized animals. Specifically, the influence of low-dose ketamine, one of three analgesics employed in the pre-hospital setting by the US Army, on haemorrhagic tolerance in humans is unknown. For the first time in conscious males and females, the findings of the present study demonstrate that the administration of an analgesic dose of ketamine does not compromise tolerance to a simulated haemorrhagic insult. Increases in muscle sympathetic nerve activity during progressive lower-body negative pressure were not different between trials. Despite the lack of differences for muscle sympathetic nerve activity responses, mean blood pressure and heart rate were higher during moderate hypovolemia after ketamine vs. placebo administration. ABSTRACT: Haemorrhage is the leading cause of battlefield and civilian trauma deaths. For a haemorrhaging soldier, there are several pain medications (e.g. ketamine) recommended for use in the prehospital, field setting. However, the data to support these recommendations are primarily limited to studies in animals. Therefore, it is unknown whether ketamine adversely affects physiological mechanisms responsible for maintenance of arterial blood pressure (BP) during haemorrhage in humans. In humans, ketamine has been demonstrated to raise resting BP, although it has not been studied with the concomitant central hypovolemia that occurs during haemorrhage. Thus, the present study aimed to test the hypothesis that ketamine does not impair haemorrhagic tolerance in humans. Thirty volunteers (15 females) participated in this double-blinded, randomized, placebo-controlled trial. A pre-syncopal limited progressive lower-body negative pressure (LBNP; a validated model for simulating haemorrhage) test was conducted following the administration of ketamine (20 mg) or placebo (saline). Tolerance was quantified as a cumulative stress index and compared between trials using a paired, two-tailed t test. We compared muscle sympathetic nerve activity (MSNA; microneurography), beat-to-beat BP (photoplethysmography) and heart rate (electrocardiogram) responses during the LBNP test using a mixed effects model (time [LBNP stage] × drug). Tolerance to the LBNP test was not different between trials (Ketamine: 635 ± 391 vs. Placebo: 652 ± 360 mmHg‧min, p = 0.77). Increases in MSNA burst frequency (time: P < 0.01, trial: p = 0.27, interaction: p = 0.39) during LBNP stages were no different between trials. Despite the lack of differences for MSNA responses, mean BP (time: P < 0.01, trial: P < 0.01, interaction: p = 0.01) and heart rate (time: P < 0.01, trial: P < 0.01, interaction: P < 0.01) were higher during moderate hypovolemia after ketamine vs. placebo administration (P < 0.05 for all, post hoc), but not at the end of LBNP. These data, which are the first to be obtained in conscious humans, demonstrate that the administration of low-dose ketamine does not impair tolerance to simulated haemorrhage or mechanisms responsible for maintenance of BP.

Burn Injury Does Not Exacerbate Heat Strain during Exercise while Wearing Body Armor.

INTRODUCTION: Although evaporative heat loss capacity is reduced in burn-injured individuals with extensive skin grafts, the thermoregulatory strain due to a prior burn injury during exercise-heat stress may be negligible if the burn is located underneath protective clothing with low vapor permeability. PURPOSE: This study aimed to test the hypothesis that heat strain during exercise in a hot-dry environment while wearing protective clothing would be similar with and without a simulated torso burn injury. METHODS: Ten healthy individuals (8 men/2 women) underwent three trials wearing: uniform (combat uniform, tactical vest, and replica torso armor plates), uniform with a 20% total body surface area simulated torso burn (uniform + burn), or shorts (and sports bra) only (control). Exercise consisted of treadmill walking (5.3 km·h; 3.7% ± 0.9% grade) for 60 min at a target heat production of 6.0 W·kg in 40.0°C ± 0.1°C and 20.0% ± 0.6% relative humidity conditions. Measurements included rectal temperature, heart rate, ratings of perceived exertion (RPE), and thermal sensation. RESULTS: No differences in rectal temperature (P ≥ 0.85), heart rate (P ≥ 0.99), thermal sensation (P ≥ 0.73), or RPE (P ≥ 0.13) occurred between uniform + burn and uniform trials. In the control trial, however, core temperature, heart rate, thermal sensation, and RPE were lower compared with the uniform and uniform + burn trials (P ≤ 0.04 for all). CONCLUSIONS: A 20% total body surface area simulated torso burn injury does not further exacerbate heat strain when wearing a combat uniform. These findings suggest that the physiological strain associated with torso burn injuries is not different from noninjured individuals when wearing protective clothing during an acute exercise-heat stress.

Dietary nitrate supplementation does not influence thermoregulatory or cardiovascular strain in older individuals during severe ambient heat stress.

NEW FINDINGS: What is the central question of this study? Does dietary nitrate supplementation with beetroot juice attenuate thermoregulatory and cardiovascular strain in older adults during severe heat stress? What is the main finding and its importance? A 7-day nitrate supplementation regimen lowered resting mean arterial pressure in thermoneutral conditions. During heat stress, core and mean skin temperatures, vasodilatory responses, sweat loss, heart rate and left ventricular function were unchanged, and mean arterial pressure was only transiently reduced, post-supplementation. These data suggest nitrate supplementation with beetroot juice does not mitigate thermoregulatory or cardiovascular strain in heat-stressed older individuals. ABSTRACT: This study tested the hypothesis that dietary nitrate supplementation with concentrated beetroot juice attenuates thermoregulatory and cardiovascular strain in older individuals during environmental heat stress. Nine healthy older individuals (six females, three males; aged 67 ± 5 years) were exposed to 42.5 ± 0.1°C and 34.0 ± 0.5% relative humidity conditions for 120 min before (CON) and after 7 days of dietary nitrate supplementation with concentrated beetroot juice (BRJ; 280 ml, ∼16.8 mmol of nitrate daily). Core and skin temperatures, body mass changes (indicative of whole-body sweat loss), skin blood flow and cutaneous vascular conductance, forearm blood flow and vascular conductance, heart rate, arterial blood pressures and indices of cardiac function were measured. The 7-day beetroot juice regimen increased plasma nitrate/nitrite levels from 27.4 ± 15.2 to 477.0 ± 102.5 µmol l-1 (P < 0.01) and lowered resting mean arterial pressure from 90 ± 7 to 83 ± 10 mmHg at baseline under thermoneutral conditions (P = 0.02). However, during subsequent heat stress, no differences in core and skin temperatures, skin blood flow and vascular conductance, forearm blood flow and vascular conductance, whole-body sweat loss, heart rate, and echocardiographic indices of systolic function and diastolic filling were evident following nitrate supplementation (all P > 0.05). Mean arterial pressure was lower in BRJ vs. CON during heat stress (treatment-by-time interaction: P = 0.02). Overall, these findings suggest that dietary nitrate supplementation with concentrated beetroot juice does not attenuate thermoregulatory or cardiovascular strain in older individuals exposed to severe ambient heat stress.

The benefits of an unsupervised exercise program in persons with well-healed burn injuries within the International Classification of Functioning, Disability and Health (ICF).

Vast improvements in the survival rates following burn injuries has led to a greater number of patients living with a wide range of long-term impairments, activity limitations, and participation constraints. Therefore, long-term care is critical in this clinical population and necessitates appropriate rehabilitation strategies to maximize an individual's overall health. The purpose of this study was to test the hypothesis that the extent to which outcomes within the International Classification of Functioning, Disability, and Health (ICF) framework are improved following 6 months of unsupervised exercise training is influenced by the severity of a burn injury (i.e., percent body surface area injured). Outcome variables representing the dimensions of the ICF, body functions & structure, activity, and participation, were collected pre- and post- 6 months of exercise training in three groups of participants: non-injured control subjects (N = 11), subjects with moderate-level well-healed burn injuries (N = 13, 26 ± 6% body surface area burned), and subjects with high-level well-healed burn injuries (N = 20, 58 ± 15% body surface area burned). Exercise training improved lower extremity strength (changes in peak torque/kg body mass at 90 degrees/sec flexion: 30 ± 5% and extension: 36 ± 4%, p < 0.05) and functional activities (changes in sit to stand: -9 ± 4% and ascend stairs: -4 ± 1%; p < 0.05) in all groups. For outcome variables representing ICF levels of body functions & structure and activity, there were no differences at baseline or improvements made between the groups after training. That said, with the exception of the domain of functional activity (reported 17 ± 34% improvement in the high-level burn cohort, p < 0.05), no changes were revealed in the participation level of ICF indexed by health-related quality of life questionnaires. These findings support the utilization of a 6-month unsupervised exercise training program in the long-term rehabilitation of individuals with burn injuries; that is, improvements in body functions & structure and activity can be achieved with an exercise regimen regardless of the severity of burn injury.

Keeping older individuals cool in hot and moderately humid conditions: wetted clothing with and without an electric fan.

The present study evaluated whether wearing a water-soaked t-shirt, with or without electric fan use, mitigates thermal and cardiovascular strain in older individuals exposed to hot and moderately humid conditions. Nine healthy older individuals (68 ± 4 yr; five women) completed three 120-min heat exposures (42.4 ± 0.2°C, 34.2 ± 0.9% relative humidity) on separate days while wearing a dry t-shirt (CON), a t-shirt soaked with 500 ml of tap water (WET), or a t-shirt soaked with 500 ml of tap water while facing an electric fan (2.4 ± 0.4 m/s; WET+FAN). Measurements included core and skin temperatures, evaporative mass losses, heart rate, and blood pressure. In the WET condition, elevations in core temperature were attenuated compared with DRY from 30 to 120 min and compared with WET+FAN from 30 to 90 min (P < 0.05). Evaporative mass losses (inclusive of sweat and water losses from the shirt) were greatest in WET+FAN, followed by WET, and then DRY (P < 0.01). Sweat losses were lowest in WET, followed by DRY, and then WET+FAN (P < 0.01). Heart rate was lower only at 60 min in WET versus DRY (P = 0.01). No differences in mean arterial pressure were observed (P = 0.51). In conclusion, wearing a water-soaked t-shirt without, but not with, electric fan use is an effective heat management strategy to mitigate thermal strain and lower sweat losses in older individuals exposed to hot and moderately humid conditions.NEW & NOTEWORTHY In older individuals exposed to hot and moderately humid environments, electric fan use coupled with a water-soaked t-shirt exacerbates sweat losses without mitigating heat strain compared with a dry t-shirt. However, wearing a water-soaked t-shirt without fan use reduces sweat losses and attenuates heat strain compared with a dry t-shirt and a fan/water-soaked t-shirt combination. These findings suggest wearing a water-soaked t-shirt is an effective heat-management strategy for older individuals during heat waves when air conditioning is inaccessible.