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Skin grafting following a burn injury attenuates/abolishes sweat production within grafted areas. It is presently unknown whether the thermoregulatory consequences of skin grafting depend on anatomical location.Purpose: 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 non-burned individuals (7 males, 2 females) 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 ± 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).Conclusion: 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.

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

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: 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 (8M/2F) underwent three trials wearing: Uniform (combat uniform, tactical vest, and replica torso armor plates), Uniform with a 20% total body surface area (TBSA) simulated torso burn (Uniform + Burn), or shorts (and sports bra) only (Control). Exercise consisted of treadmill walking (5.3 km·h(–1); 3.7 ± 0.9% grade) for 60 min at a target heat production of 6.0 W·kg(−1) in 40.0 ± 0.1°C; 20.0 ± 0.6% relative humidity conditions. Measurements included rectal temperature, heart rate, rating of perceived exertion, and thermal sensation. RESULTS: No differences in rectal temperature (P ≥ 0.85), heart rate (P ≥ 0.99), thermal sensation (P ≥ 0.73), or rating of perceived exertion (P ≥ 0.13) occurred between Uniform + Burn and Uniform trials. In the Control trial, however, core temperature, heart rate, thermal sensation, and rating of perceived exertion were lower compared to the Uniform and Uniform + Burn trials (P ≤ 0.04 for all). CONCLUSION: A 20% TBSA 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 non-injured individuals when wearing protective clothing during an acute exercise-heat stress.

Purpose Upper-body exercise performed in a cold environment may increase cardiovascular strain, which could be detrimental to patients with coronary artery disease (CAD). This study compared cardiovascular responses of CAD patients during graded upper-body dynamic and static exercise in cold and neutral environments. Methods 20 patients with stable CAD performed 30 min of progressive dynamic (light, moderate, and heavy rating of perceived exertion) and static (10, 15, 20, 25 and 30% of maximal voluntary contraction) upper body exercise in cold (− 15 °C) and neutral (+ 22 °C) environments. Heart rate (HR), blood pressure (BP) and electrocardiographic (ECG) responses were recorded and rate pressure product (RPP) calculated. Results Dynamic-graded upper-body exercise in the cold increased HR by 2.3–4.8% (p = 0.002–0.040), MAP by 3.9–5.9% (p = 0.038–0.454) and RPP by 18.1–24.4% (p = 0.002–0.020) when compared to the neutral environment. Static graded upper-body exercise in the cold resulted in higher MAP (6.3–9.1%; p = 0.000–0.014), lower HR (4.1–7.2%; p = 0.009–0.033), but unaltered RPP compared to a neutral environment. Heavy dynamic exercise resulted in ST depression that was not related to temperature. Otherwise, ECG was largely unaltered during exercise in either thermal condition. Conclusions Dynamic- and static-graded upper-body exercise in the cold involves higher cardiovascular strain compared with a neutral environment among patients with stable CAD. However, no marked changes in electric cardiac function were observed. The results support the use of upper-body exercise in the cold in patients with stable CAD. Trial registration Clinical trial registration NCT02855905 August 2016.

Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a pre-syncopal limited progressive lower-body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg•min), which was compared between trials using a paired, two-tailed t test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model (time [LBNP stage] x trial). LBNP tolerance was not different between trials (Fentanyl: 647 ± 386 vs. Placebo: 676 ± 295 mmHg•min, P = 0.61, Cohen's d = 0.08). Increases in MSNA burst frequency (time: P < 0.01, trial: P = 0.29, interaction: P = 0.94) and reductions in mean BP (time: P < 0.01, trial: P = 0.50, interaction: P = 0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.

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.

Due to improvements in acute burn care over the last few decades, most patients with severe burns (up to 90% of the total body surface) survive. However, the metabolic and cardiovascular complications that accompany a severe burn can persist for up to 3 years post injury. Accordingly, there is now a greater appreciation of the need for strategies that can hasten recovery and reduce long-term morbidity post burn. Rehabilitation exercise training (RET) is a proven effective treatment to restore lean body mass, glucose and protein metabolism, cardiorespiratory fitness, and muscle strength in burn survivors. Despite this, very few hospitals incorporate RET in programs to aid the rehabilitation of patients with severe burns. Given that RET is a safe and efficacious treatment that restores function and reduces post-burn morbidity, we propose that a long-term exercise prescription plan should be considered for all patients with severe burns. In this literature review, we discuss the current understanding of burn trauma on major organ systems, and the positive benefits of incorporating RET as a part of the long-term rehabilitation of severely burned individuals. We also provide burn-specific exercise prescription guidelines for clinical exercise physiologists.

There is considerable interindividual variability in the perception of pain. Given that pain management is a major public health problem, gaining insight into the underlying physiology of these perceptual differences is important. We tested the hypothesis that when interindividual variability in initial muscle sympathetic nerve activity (MSNA) responses to a cold pressor test (CPT) is identified, the divergent responses will be linked to differences in pain perception in healthy young men and women. In the supine position, blood pressure (BP) and MSNA were measured at baseline and during a 2-min CPT. Immediately following the CPT, pain was rated (range 0–10). Two groups were established: positive responders (Pos, n = 12) and negative responders (Neg, n = 12) based on the initial (first 30 s) MSNA response profiles (Pos: 12 ± 9, Neg: −3 ± 3 bursts/min, P

Background Supine hypertension affects a majority of patients with autonomic failure; it is associated with end‐organ damage and can worsen daytime orthostatic hypotension by inducing pressure diuresis and volume loss during the night. Because sympathetic activation prevents blood pressure (BP) from falling in healthy subjects exposed to heat, we hypothesized that passive heat had a BP‐lowering effect in patients with autonomic failure and could be used to treat their supine hypertension. Methods and Results In Protocol 1 (n=22), the acute effects of local heat (40–42°C applied with a heating pad placed over the abdomen for 2 hours) versus sham control were assessed in a randomized crossover fashion. Heat acutely decreased systolic BP by −19±4 mm Hg (versus 3±4 with sham, P P =0.013 ) and cardiac output (−15±5% versus −2±4%, P =0.013). In Protocol 2 (proof‐of‐concept overnight study; n=12), we compared the effects of local heat (38°C applied with a water‐perfused heating pad placed under the torso from 10 pm to 6 am ) versus placebo pill. Heat decreased nighttime systolic BP (maximal change −28±6 versus −2±6 mm Hg, P am . The nocturnal systolic BP decrease correlated with a decrease in urinary volume ( r =0.57, P =0.072) and an improvement in the morning upright systolic BP ( r =−0.76, P =0.007). Conclusions Local heat therapy effectively lowered overnight BP in patients with autonomic failure and supine hypertension and offers a novel approach to treat this condition. Future studies are needed to assess the long‐term safety and efficacy in improving nighttime fluid loss and daytime orthostatic hypotension. Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT02417415 and NCT03042988.

INTRODUCTION. Vasodilator function is impaired in individuals with well-healed burn injuries, but 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 post-training. METHODS. Microvascular function, (forearm reactive hyperemia), macrovascular function (brachial artery flow-mediated dilation), and the maximal vasodilatory response following ischemic handgrip exercise (an estimate of microvascular remodeling) were assessed before and after exercise training in non-burned 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 post-occlusive reactive hyperemia increased from pre- to post-training 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 following 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). CONCLUSION. 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.

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 0.05). 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.

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

We investigated that the effects of hypercapnia-induced elevations in cerebral perfusion during a heat stress on global cerebrovascular responses to an orthostatic challenge. Seven volunteers completed a progressive lower-body negative pressure (LBNP) challenge to presyncope during heat stress, with or without breathing a hypercapnic gas mixture. Administration of the hypercapnic gas mixture increased the partial pressure of end-tidal CO2 greater than pre-heat stress alone, and increased both internal carotid artery (ICA) and vertebral artery (VA) blood flows (P P

NEW FINDINGS What is the central question of this study? The venoarteriolar response (VAR) contributes substantially to the maintenance of orthostatic tolerance in humans. Despite its importance in haemodynamic homeostasis, the impact of ageing on the VAR remains understudied. What is the main finding and its importance? Older adults exhibit an augmented VAR in response to leg dependency. The age-related augmentation of the VAR might be linked with progressive increases of peripheral vascular resistance with ageing. We found a modest but significant correlation between the leg VAR and the morning blood pressure surge in older adults. Augmented leg VAR might contribute to the blood pressure elevation in the early morning. ABSTRACT The venoarteriolar response (VAR) is a non-adrenergic, non-baroreflex-mediated mechanism of vasoconstriction, which has been proposed to contribute ∼45% of the increase in total peripheral resistance during orthostasis. Despite its importance in human cardiovascular control during orthostatic stress, there is no information available regarding the impact of age and sex on the VAR or its role in diurnal blood pressure (BP) variation. We studied 33 (15 women) young (mean ± SD; 28 ± 4 years old) and 26 (12 women) older (71 ± 3 years old) healthy individuals. Brachial and femoral blood flow were measured using Doppler ultrasound. The percentage reduction in vascular conductance (blood flow/mean BP) during 4 min of limb dependency (35-40 cm below the heart level) was used to assess the VAR. The morning surge in BP was assessed using 24 h ambulatory BP monitoring. Peak VAR in the lower limb, but not in the upper limb, was significantly higher in the older than the younger adults (33 ± 4 versus 26 ± 6%, older versus young; P < 0.05). There was no sex difference in the VAR in either the young or the older group. A greater leg VAR was related to a greater morning surge in BP in older adults (r = -0.4, P = 0.02) but not in the young adults (r = -0.26, P = 0.1). Thus, advancing age enhances the VAR in the lower limb and is associated with the morning blood pressure surge in older adults. Sex does not affect this local axonal reflex in healthy humans.

Objective To determine if a healthy newborn's age in hours (3, 6, or 9 hours after birth) affects thermoregulatory status after the first bath as indicated by axillary and skin temperatures. Design Quasi-experimental, mixed-model (between subjects and within subjects) design with hours of age as the nonrepeated variable and prebath and postbath temperatures as the repeated variables. Setting Family-centered care unit at an urban hospital in the southwestern United States. Participants Healthy newborns (N = 75) 37 weeks or more completed gestation. Methods Mothers chose time of first bath based on available time slots (n = 25 newborns in each age group). Research nurses sponge bathed the newborns in the mothers' rooms. Axillary temperature, an index of core temperature, was measured with a digital thermometer, and skin temperature, an index of body surface temperature, was measured with a thermography camera. Temperatures were taken before the bath; immediately after the bath; and 5, 30, 60, and 120 minutes after the bath. Immediately after the bath, newborns were placed in skin-to-skin care (SSC) for 60 or more minutes. Results We found a difference (p = .0372) in axillary temperatures between the 3- and 9-hour age groups, although this difference was not clinically significant (0.18 °F [0.10 °C]). We found no statistically significant differences in skin temperatures among the three age groups. Regardless of age group, axillary and skin temperatures initially decreased and then recovered after the bath. Conclusion For up to 2 hours postbath, axillary and skin temperatures were not different between healthy newborns bathed at 3, 6, or 9 hours of age. Thermography holds promise for learning about thermoregulation, bathing, and SSC.

Following exercise, mean arterial pressure (MAP) is reduced ~5–10 mmHg from preexercise baseline. In nonendurance-trained males, postexercise hypotension results from peripheral vasodilation not offset by increased cardiac output (CO). By contrast, postexercise hypotension occurs through a reduction in CO from preexercise baseline in endurance-trained males. The reason(s) explaining these divergent responses remain unknown. Exercise at fixed percentage of peak oxygen consumption (V̇o2peak) is associated with a greater rate of metabolic heat production in trained individuals and therefore elevated sweat rates, both when compared with untrained individuals. We hypothesized that greater fluid loss would explain the postexercise reduction in CO of endurance-trained males. Twelve endurance-trained males (Trained: V̇o2peak, 64 ± 5 ml O2·kg−1·min−1) cycled for 60 min at 60% V̇o2peak (Trained60%). On separate days, 12 nonendurance trained males (Untrained: V̇o2peak, 49 ± 3 ml O2·kg−1·min−1) cycled at 1) 60% V̇o2peak (Untrained60%), and 2) a rate of heat production equivalent to that achieved by the Trained group (UntrainedMatched). Fluid loss was similar between Trained60% (−1.32 ± 0.20 kg) and UntrainedMatched (−1.32 ± 0.23 kg; P = 0.99) but was greater in these conditions relative to Untrained60% (−0.95 ± 0.11 kg; both P < 0.01). During the final 30 min of postexercise supine recovery, MAP was similarly reduced by 5 ± 2 mmHg in all three conditions ( P = 0.91). The reduction in MAP was mediated by a 0.5 ± 0.3 l/min reduction in CO from baseline in Trained60% ( P = 0.01). In contrast, CO returned to baseline following exercise during UntrainedMatched and Untrained60% (both P ≥ 0.30). These data demonstrate that greater fluid loss does not fully explain the divergent postexercise hemodynamic responses observed in trained relative to untrained males. NEW & NOTEWORTHY Even when matched for exercise-induced fluid loss, cardiac output was decreased in trained males but returned to baseline following exercise in their untrained counterparts. However, as per our hypothesis, reductions in stroke volume were similar between groups. This suggests that exercise-induced fluid loss is an important determinant of the stroke volume response during recovery but factors affecting heart rate such as exercise intensity and/or heat stress are also important determinants of postexercise hemodynamics.

Physical movement lasting any more than a few seconds (e.g., exercise), requires coordination of motor control with concomitant changes in the cardiovascular and respiratory support necessary to respond to the rapid increases in metabolic demand. Without such coordination, delivery of oxygen and removal of waste products become rate limiting and will restrict the duration, speed, and quality of movement. Fortunately, under healthy conditions, the central and peripheral nervous systems contribute importantly to this remarkable level of coordination via complex mechanisms that remain to be fully elucidated. The purposes of this review are to present the current state of knowledge regarding: (i) mechanisms by which the body maintains appropriate perfusion pressure to all organs during acute bouts of exercise, and (ii) alterations occurring in these mechanisms via central nervous system adaptations when exercise is performed or not performed on a regular basis (e.g., physically active versus sedentary lifestyle, respectively). Results from studies performed in humans and laboratory animals provide the reader a well-rounded knowledge base. They are intended to instill an appreciation of what is known, and not known, about how the brain regulates the cardiovascular system during acute bouts of exercise, and the adaptations that occur when individuals exercise regularly versus when chronically sedentary. Discussion of the latter is intended to provide novel mechanisms for the increased incidence of cardiovascular disease in sedentary individuals versus a reduced incidence in individuals who are regularly active. © 2018 American Physiological Society. Compr Physiol 8:103-151, 2018.

Skeletal muscle blood flow is attenuated in aged humans performing dynamic exercise, which is due, in part, to impaired local vasodilatory mechanisms. Recent evidence suggests that folic acid improves cutaneous vasodilation during localized and whole body heating through nitric oxide-dependent mechanisms. However, it is unclear whether folic acid improves vasodilation in other vascular beds during conditions of increased metabolism (i.e., exercise). The purpose of this study was to test the hypothesis that folic acid ingestion improves skeletal muscle blood flow in aged adults performing graded handgrip and plantar flexion exercise via increased vascular conductance. Nine healthy, aged adults (two men and seven women; age: 68 ± 5 yr) performed graded handgrip and plantar flexion exercise before (control), 2 h after (acute, 5 mg), and after 6 wk (chronic, 5 mg/day) folic acid ingestion. Forearm (brachial artery) and leg (superficial femoral artery) blood velocity and diameter were measured via Duplex ultrasonography and used to calculate blood flow. Acute and chronic folic acid ingestion increased serum folate (both P < 0.05 vs. control). During handgrip exercise, acute and chronic folic acid ingestion increased forearm blood flow (both conditions P < 0.05 vs. control) and vascular conductance (both P < 0.05 vs. control). During plantar flexion exercise, acute and chronic folic acid ingestion increased leg blood flow (both P < 0.05 vs. control), but only acute folic acid ingestion increased vascular conductance ( P < 0.05 vs. control). Taken together, folic acid ingestion increases blood flow to active skeletal muscle primarily via improved local vasodilation in aged adults.NEW & NOTEWORTHY Our findings demonstrate that folic acid ingestion improves blood flow via enhanced vascular conductance in the exercising skeletal muscle of aged humans. These findings provide evidence for the therapeutic use of folic acid to improve skeletal muscle blood flow, and perhaps exercise and functional capacity, in human primary aging.Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/folic-acid-and-exercise-hyperemia-in-aging/ .

Background Multiple sclerosis (MS) is a neurological disease marked by demyelination and axonal loss. Individuals with MS experience increases in clinical signs and symptoms during heat exposure. Objective To test the hypothesis that moderate heat exposure adversely affects postural sway in individuals with MS. Methods Ten individuals with relapsing-remitting MS (50 ± 8y) and nine controls (47 ± 10y) were examined under a Thermal and a Time Control trial. Following a 30 min thermoneutral baseline (25 °C, 30% relative humidity (RH)), stand tests randomized with eyes open and closed, were performed. For Thermal, subjects were first exposed to 60 min of heating (40 °C, 30%RH) followed by 60 min of cooling (20 °C, 30%RH). For Time Control, subjects remained in a thermoneutral environment throughout. Stand tests were repeated at consistent times in both trials. Results No difference in skin and core temperatures between groups were observed for any trial (P > 0.05). During heating, postural sway was higher in MS relative to control subjects (eyes open, P = 0.03; eyes closed, P = 0.011). No differences in postural sway, regardless of eye status, were observed during the Time Control trial for either group (P > 0.05). Conclusion These data demonstrate that exposure to a moderate heating environment increases postural sway in patients with MS.

Local heating of an extremity increases blood flow and vascular shear stress throughout the arterial tree. Local heating acutely improves macrovascular dilator function in the upper limbs of young healthy adults through a shear stress-dependent mechanism but has no such effect in the lower limbs of this age group. The effect of acute limb heating on dilator function within the atherosclerotic prone vasculature of the lower limbs of aged adults is unknown. Therefore, the purpose of this study was to test the hypothesis that acute lower limb heating improves macro- and microvascular dilator function within the leg vasculature of aged adults. Nine young and nine aged adults immersed their lower limbs at a depth of ~33 cm into a heated (~42°C) circulated water bath for 45 min. Before and 30 min after heating, macro (flow-mediated dilation)- and microvascular (reactive hyperemia) dilator functions were assessed in the lower limb, following 5 min of arterial occlusion, via Doppler ultrasound. Compared with preheat, macrovascular dilator function was unchanged following heating in young adults ( P = 0.6) but was improved in aged adults ( P = 0.04). Similarly, microvascular dilator function, as assessed by peak reactive hyperemia, was unchanged following heating in young adults ( P = 0.1) but was improved in aged adults ( P < 0.01). Taken together, these data suggest that acute lower limb heating improves both macro- and microvascular dilator function in an age dependent manner. NEW & NOTEWORTHY We demonstrate that lower limb heating acutely improves macro- and microvascular dilator function within the atherosclerotic prone vasculature of the leg in aged adults. These findings provide evidence for a potential therapeutic use of chronic lower limb heating to improve vascular health in primary aging and various disease conditions.

Introduction Excision of burned skin and subsequent grafting removes sweat glands and thereby impairs thermoregulation. Consequently, rehabilitation and associated exercise may be accompanied by a greater risk of hyperthermia, depending on exercise duration, intensity and environmental temperature. Current physical activity guidelines recommend adults perform at least 150 min of moderate-intensity exercise per week, which is often divided into 30-min daily sessions. This project tested the hypothesis that burn survivors could exercise for 30 min without excessive elevations in core body temperature, regardless of the total body surface area (%TBSA) burned or environmental temperature. Methods Ten subjects cycled for 60 min at 1) a moderate intensity (97±8 watts) in a thermoneutral environment (24°C, MOD_NEU), 2) a moderate intensity (100±17 watts) in a hot environment (39°C, MOD_HOT), and 3) a low intensity (65±10 watts) in a hot environment (39°C, LOW_HOT). Burn injuries were simulated by covering 0%, 20%, 40%, or 60% of the individual’s TBSA with an absorbent material that prevented sweat evaporation. Changes in gastrointestinal temperature (ΔTcore) were analyzed at 15-min increments throughout exercise. Results For the MOD_NEU trial, there were no differences in ΔTcore between the %TBSA coverage bouts at any time point during exercise. For the MOD_HOT trial, there were no differences in ΔTcore at 15 and 30 min of exercise regardless of the %TBSA coverage, while ΔTcore was appreciably elevated (P< 0.05) at 45 and 60 min of exercise for 20%+ TBSA bouts. For the MILD_HOT trial, there were no differences in ΔTcore at any time point between %TBSA bouts, with the sole exception of 60% simulated burn having a slightly greater ΔTcore (0.3±0.34°C; P< 0.05) at 60 min of exercise relative to the 0% TBSA bout. Conclusions These data indicate that individuals with up to 60% of their TBSA burned could exercise at a moderate intensity for 30 min, even in hot environmental conditions, without excessive elevations in body core temperature. Applicability of Research to Practice Individuals with significant burn injuries can benefit from exercise, without the risk of excessive hyperthermia, for up to 30 min in the heat or at least 60 min in an air conditioned space. Funding: DOD W81XWH-15-1-0647

BACKGROUND Regular long-term physical exercise has favourable effects on endothelial function in patients with coronary artery disease (CAD). However, the effects of an acute exercise bout in the cold on endothelial function are not known. METHODS At first, the effects of moderate-intensity aerobic lower-body exercise were assessed in CAD patients (n = 16) in a neutral [+22°C] and cold [-15°C] environment. Secondly, responses to static and dynamic upper-body exercise in a neutral [+22°C] and cold [-15°C] environment were investigated in CAD patients (n = 15). All experiments were performed in a random order. Endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery in response to reactive hyperaemia, before and after the exposures in a neutral environment. RESULTS No significant temperature*exercise*condition (pre-post) interaction was observed in FMD% when comparing rest versus aerobic exercise or static versus dynamic upper-body exercise. Relative reactive hyperaemia during FMD protocol, measured by changes in shear rate, was elevated after rest compared to aerobic exercise (p = .001) and after static compared to dynamic upper-body exercise (p

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.

The U.S. Army’s Standards of Medical Fitness (AR 40-501) states: “Prior burn injury (to include donor sites) involving a total body surface area of 40 percent or more does not meet the standard”. However, the standard does not account for the interactive effect of burn injury size and air temperature on exercise thermoregulation. PURPOSE: To evaluate whether the detrimental effect of a simulated burn injury on exercise thermoregulation is dependent upon air temperature. METHODS: On eight occasions, nine males cycled for 60 min at a fixed metabolic heat production (6 W·kg(−1)) in air temperatures of 40°C or 25°C with simulated burn injuries of 0% (Control), 20%, 40%, or 60% of total body surface area (TBSA). Burn injuries were simulated by covering the skin with an absorbent, vapor-impermeable material to impede evaporation from the covered areas. Core temperature was measured in the gastrointestinal tract via telemetric pill. RESULTS: In 40°C conditions, greater elevations in core temperature were observed with 40% and 60% TBSA simulated burn injuries vs. Control (P < 0.01). However, at 25°C, core temperature responses were not different vs. Control with 20%, 40%, and 60% TBSA simulated injuries (P = 0.97). The elevation in core temperature at the end of exercise was greater in the 40°C environment with 20%, 40% and 60% TBSA simulated burn injuries (P ≤ 0.04). CONCLUSION: Simulated burn injuries ≥20% TBSA exacerbate core temperature responses in hot, but not temperate, air temperatures. These findings suggest that the U.S. Army’s standard for inclusion of burned soldiers is appropriate for hot conditions, but could lead to the needless discharge of soldiers who could safely perform their duties in cooler training/operational settings.

Supine hypertension affects about half of patients with primary autonomic failure (AF), complicates the treatment of orthostatic hypotension (OH) and induces nocturnal polyuria, resulting in worsening of morning OH. We previously showed that short exposure to local passive heat (40-42°C applied for ≤2 hours over abdomen and pelvis with a heating pad) acutely decreased systolic blood pressure (BP) by -25±5 mmHg in AF patients with supine hypertension due to decreases in stroke volume (-29±5%) and cardiac output (-30±5%). In this study, we hypothesized that local passive heat therapy applied overnight would lower nocturnal BP and polyuria, and improve early morning OH in these patients. Ten AF patients with supine hypertension (age 76±2 years, 6 men, supine systolic BP 168±3 mmHg) received passive heat (38°C with a water-perfused heating pad placed under the torso) or placebo, in a 2-night crossover study. Supine BP was monitored every 2 hr from 8pm-8am. Heat therapy was applied from 10pm-6am. Morning orthostatic tolerance was assessed at 8 am. Systolic BP significantly decreased during overnight heat therapy compared to placebo (Figure; P

Menopausal hot flushes negatively impact quality of life and may be a biomarker of cardiovascular and metabolic disease risk; therefore understanding the physiology of hot flushes is important. Current thinking is that a small elevation (∼0.03-0.05C) in core temperature surpasses a sweating threshold (that is reduced in the menopause), sweating is activated, and a hot flush ensues. Nevertheless, more recent studies examining thermoregulatory control question whether core temperature per se can explain the trigger for a hot flush. The primary aim of this study was to assess the contribution of increases in core temperature on the occurrence of menopausal hot flushes.For this purpose, 108 hot flushes were objectively assessed in a laboratory setting in 72 symptomatic postmenopausal women (aged 45.8 ± 5.1 years; body mass index 25.9 ± 4.5 kg/m) from five previously reported studies. Women rested, wearing a tube-lined suit (or trousers), which was perfused with 34C water. A subset then underwent mild heat stress (48°C water). Sweat rate, skin blood flow, blood pressure, heart rate, skin, and core temperature were measured continuously throughout. A hot flush was objectively identified during rest (spontaneous hot flush) or mild heating as an abrupt increase in sternal sweat rate. Further, a subset of symptomatic postmenopausal women (n = 22) underwent whole-body passive heating for 60 minutes to identify core temperature thresholds and sensitivities for sweat rate and cutaneous vasodilation, which were compared to a subset of premenopausal women (n = 18). Data were analyzed using t tests and/or general linear modeling, and are presented as mean (95% confidence interval).In the 20 minutes before a spontaneous hot flush, core temperature increased by 0.03 ± 0.12C (P 0.05), but only 51% of hot flushes were preceded by an increase in core temperature. During mild heating, 76% of hot flushes were preceded by an increase in core temperature. The temperature thresholds for sweating were similar, but the vasodilatory threshold was higher in postmenopausal compared with premenopausal women (37.1 ± 0.2 vs 36.8 ± 0.3°C; P = 0.06).We provide new evidence that menopausal hot flushes are unlikely triggered by an increase in core temperature. These findings provide important information about the physiology of hot flushes that have implications for treatment and management options for menopausal hot flushes.

Long-term rehabilitative strategies are important for individuals with well-healed burn injuries. Such information is particularly critical because patients are routinely surviving severe burn injuries given medical advances in the acute care setting. The purpose of this study was to test the hypothesis that a 6-mo community-based exercise training program will increase maximal aerobic capacity (V̇o2max) in subjects with prior burn injuries, with the extent of that increase influenced by the severity of the burn injury (i.e., percent body surface area burned). Maximal aerobic capacity (indirect calorimetry) and skeletal muscle oxidative enzyme activity (biopsy of the vastus lateralis muscle) were measured pre- and postexercise training in noninjured control subjects ( n = 11) and in individuals with well-healed burn injuries ( n = 13, moderate body surface area burned; n = 20, high body surface area burned). Exercise training increased V̇o2max in all groups (control: 15 ± 5%; moderate body surface area: 11 ± 3%; high body surface area: 11 ± 2%; P < 0.05), though the magnitude of this improvement did not differ between groups ( P = 0.7). Exercise training also increased the activity of the skeletal muscle oxidative enzymes citrate synthase ( P < 0.05) and cytochrome c oxidase ( P < 0.05), an effect that did not differ between groups ( P = 0.2). These data suggest that 6 mo of progressive exercise training improves V̇o2max in individuals with burn injuries and that the magnitude of body surface area burned does not lessen this adaptive response.

Passive hyperthermic exposure causes an acute hypotensive response following the cessation of heat stress. Chronic heat stress is well documented in animal studies to instigate metabolic and lipid alterations. However, it is unknown if exercise-heat acclimation also causes favorable chronic blood pressure, lipid, and immune responses in humans.This project tested the hypothesis that 10-day exercise-heat acclimation (HA) would cause greater post-exercise reductions in arterial blood pressure and favorable metabolic, lipid, and immune responses compared to 10-day exercise under neutral conditions (CON).Thirteen healthy sedentary participants (8M/5F, 28 ± 6y, 78 ± 17 kg), completed a 10-day (90 min/day exercise bout) clamped hyperthermia HA (increase internal temperature 1.5 °C, in 42 °C, 28% Rh) and control (CON: 23 °C, 42% Rh) protocols in a counterbalanced design with a 2 month washout. Pre- and post-exercise HA/CON blood pressures were taken 1-h post-exercise on exercise days 1 and 10. Metabolic, lipid and immune panels were taken pre-post HA/CON.Exercise under heat stress had greater post-exercise hypotension (systolic; -6 mmHg, diastolic; -8 mmHg; and mean arterial pressure; -7 mmHg) on both days 1 and 10 compared to exercise under neutral conditions (main effect for condition, P ≤ 0.004). Only from pre-to-post HA, total cholesterol (168 ± 19 to 157 ± 15; P 0.03) and triglycerides (137 ± 45 to 111 ± 30; P 0.03) were reduced, while absolute lymphocytes (-26%), monocytes (-22%), and basophils (-49%) significantly decreased (each P ≤ 0.04). Relative values of neutrophils increased (18%) and lymphocytes decreased (-20%) only after HA (P ≤ 0.04).These data indicate that exercise in the heat (regardless of acclimation status) causes a profound post-exercise hypotensive response, while HA causes favorable lipid, and immune profile changes. Further examination of exercise-heat acclimation on vascular, metabolic, and immune responses will offer insight for benefits in other clinical populations with vascular, metabolic and immune dysfunction.

We tested the hypothesis that whole‐body passive heat stress reduces arterial stiffness in older adults. At preheat stress (baseline) and when core temperature was elevated by 0.6 ± 0.2°C (mild) and 1.2 ± 0.3°C (moderate), arterial stiffness was measured in eight healthy younger (26 ± 5 years) and eight healthy older (70 ± 4 years) adults in the supine position. Arterial stiffness was estimated from carotid‐to‐femoral pulse wave velocity (cfPWV, applanation tonometry). cfPWV was higher at baseline in older adults (8.8 ± 2.3 m/sec vs. 5.6 ± 0.9 m/sec, P

The U.S. Army’s Standards of Medical Fitness, AR 40–501, state that “Prior burn injury (to include donor sites) involving a total body surface area of 40 percent or more does not meet the standard”. Inclusion of donor sites (sites harvested for skin grafts) in this Standard implies that thermoregulatory function is impaired within donor sites during exercise-heat stress; however, supporting evidence is currently lacking. PURPOSE: To test the hypothesis that well-healed donor and non-injured sites demonstrate similar elevations in skin blood flow and sweating during exercise-induced hyperthermia. METHODS: Twenty burn survivors (>1 year post-injury; four females) cycled for 60 min in a 39.7 ± 0.3°C and 21.1 ± 3.3% relative humidity environment at ~50% of maximal aerobic capacity. Core and mean skin temperatures were recorded throughout exercise. Skin blood flow (laser-Doppler imaging) was measured at baseline and after exercise within donor (LDF(DON)) and adjacent non-injured control (LDF(CON)) sites. At 45 min of exercise, local sweat rates (Technical Absorbents) were measured within the same donor (LSR(DON)) and non-injured (LSR(CON)) areas. RESULTS: After 60 min of exercise, core and skin temperatures reached 38.2 ± 0.4°C and 35.5 ± 1.2°C, respectively. The increase in skin blood flow from baseline to end-exercise (LDF(DON): 91.6 ± 44.5 AU; LDF(CON): 106.0 ± 61.6 AU; P = 0.17) and local sweat rates (LSR(DON): 0.46 ± 0.26 mg cm(−2) min(−1); LSR(CON): 0.53 ± 0.25 mg cm(−2) min(−1); P = 0.14) were not different between donor and non-injured control sites. CONCLUSION: Well-healed donor sites retain the ability to increase skin blood flow and sweating during exercise-heat stress, providing evidence against the inclusion of donor sites when determining whether a burn injury meets the Army’s Standards of Medical Fitness.

Long-term burn survivors have reduced aerobic capacity, placing them at increased risk for cardiovascular disease, morbidity, and mortality. However, the exact mechanism contributing to a reduced aerobic capacity remains incompletely understood, but may be related to adverse cardiovascular remodeling. Therefore, it was hypothesized that well-healed burn survivors would exhibit adverse left ventricular (LV) remodeling and impaired LV function. To test this hypothesis, 22 well-healed moderately burned individuals (age: 41 ± 14 years; BMI: 27.7 ± 5.4 kg/m(2); male/female: 12/10; extent of burn: 37 ± 12 %BSA), 11 well-healed severely burned individuals (age: 43 ± 12 years; BMI: 29.5 ± 5.8 kg/m(2); male/female: 8/3; extent of burn: 73 ± 11 %BSA), and 12 healthy, age-matched controls (age: 34 ± 9 years; BMI: 28.6 ± 5.2 kg/m(2); male/female: 5/7) were enrolled in the study. All subjects were sedentary, performing less than 30 minutes of aerobic exercise per day, 3 days per week. LV morphology and function were assessed via cardiac magnetic resonance imaging. In contrast to the hypothesis, neither the presence nor severity of burn injury adversely affected LV morphology or function, when compared with equally sedentary nonburned controls. However, of note, LV mass of all three groups was in the lowest 5th percentile compared with normative values. Finally, group differences in LV morphology were largely explained by differences in aerobic capacity. Taken together, these data suggest a prior burn injury itself does not result in pathological remodeling of the LV and support a role for aerobic exercise training to improve cardiac function.

During heat stress, stroke volume is maintained in young adults despite reductions in cardiac filling pressures. This is achieved by a general augmentation of cardiac function, highlighted by a left and upward shift of the Frank-Starling relation. In contrast, healthy aged adults are unable to maintain stroke volume during heat stress. We hypothesized that this would be associated with a lack of shift in the Frank-Starling relation. Frank-Starling relations were examined in 11 aged [69 ± 4 (SD) yr, 4 men/7 women] and 12 young (26 ± 5 yr, 6 men/6 women) adults during normothermic and heat stress (1.5°C increase in core temperature) conditions. During heat stress, increases in cardiac output were attenuated in aged adults (+2.5 ± 0.3 (95% CI) vs. young: +4.5 ± 0.5 l/min, P < 0.01) because of an attenuated chronotropic response (+30 ± 4 vs. young: +42 ± 5 beats/min, P < 0.01). In contrast to our hypothesis, a leftward shift of the Frank-Starling relation maintained stroke volume during heat stress in aged adults (76 ± 8 vs. normothermic: 74 ± 8 ml, P = 0.38) despite reductions in cardiac filling pressure (6.6 ± 1.0 vs. normothermic: 8.9 ± 1.1 mmHg, P < 0.01). In a subset of participants, volume loading was used to return cardiac filling pressure during heat stress to normothermic values, which resulted in a greater stroke volume for a given cardiac filling pressure in both groups. These results demonstrate that the Frank-Starling relation shifts during heat stress in healthy young and aged adults, thereby preserving stroke volume despite reductions in cardiac filling pressures.

One in 10 deaths worldwide is caused by traumatic injury, and 30% to 40% of those trauma-related deaths are due to hemorrhage. Currently, warming a bleeding victim is the standard of care due to the adverse effects of combined hemorrhage and hypothermia on survival. We tested the hypothesis that heating is detrimental to the maintenance of arterial pressure and cerebral perfusion during hemorrhage, while cooling is beneficial to victims who are otherwise normothermic. Twenty-one men (31 ± 9 y) were examined under two separate protocols designed to produce central hypovolemia similar to hemorrhage. Following 15 min of supine rest, 10 min of 30 mm Hg of lower body negative pressure (LBNP) was applied. On separate randomized days, subjects were then exposed to skin surface cooling (COOL), warming (WARM), or remained thermoneutral (NEUT), while LBNP continued. Subjects remained in these thermal conditions for either 40 min of 30 mm Hg LBNP (N = 9), or underwent a continuous LBNP ramp until hemodynamic decompensation (N = 12). Arterial blood pressure during LBNP was dependent on the thermal perturbation as blood pressure was greater during COOL (P >0.001) relative to NEUT and WARM for both protocols. Middle cerebral artery blood velocity decreased (P

Acute and chronic hyperthermic treatments in diabetic animal models repeatedly improve insulin sensitivity and glycemic control. Therefore, the purpose of this study was to test the hypothesis that an acute 1h bout of hyperthermic treatment improves glucose, insulin, and leptin responses to an oral glucose challenge (OGTT) in obese type 2 diabetics and healthy humans. Nine obese (45±7.1% fat mass) type 2 diabetics (T2DM: 50.1±12y, 7.5±1.8% HbA1c) absent of insulin therapy and nine similar aged (41.1±13.7y) healthy non-obese controls (HC: 33.4±7.8% fat mass, P

Comment on: Ravanelli NM, Jay O. Electric fan use in heat waves: Turn on or turn off? Temperature. 2016;3:358–360. doi:10.1080/23328940.2016.1211073.

Regular year-round exercise is recommended for patients with coronary artery disease (CAD). However, the combined effects of cold and moderate sustained exercise, both known to increase cardiac workload, on cardiovascular responses are not known. We tested the hypothesis that cardiac workload is increased, and evidence of ischemia would be observed during exercise in the cold in patients with CAD. Sixteen men (59.3 +/- 7.0 yr, means +/- SD) with stable CAD each underwent 4, 30 min exposures in a randomized order: seated rest and moderate-intensity exercise [walking, 60%-70% of max heart rate (HR)] performed at +22 degrees C and -15 degrees C. Systolic brachial blood pressure (SBP), HR, electrocardiogram (ECG), and skin temperatures were recorded throughout the intervention. Rate pressure product (RPP) and ECG parameters were obtained. The combined effects of cold and submaximal exercise were additive for SBP and RPP and synergistic for HR when compared with rest in a neutral environment. RPP (mmHg.beats/min) was 17% higher during exercise in the cold (18,080 +/- 3540) compared with neutral (15,490 +/- 2,940) conditions (P = 0.001). Only a few ST depressions were detected during exercise but without an effect of ambient temperature. The corrected QT interval increased while exercising in the cold compared with neutral temperature (P = 0.023). Recovery of postexercise blood pressure was similar regardless of temperature. Whole body exposure to cold during submaximal exercise results in higher cardiac workload compared with a neutral environment. Despite the higher RPP, no signs of myocardial ischemia or abnormal ECG responses were observed. The results of this study are useful for planning year-round exercise-based rehabilitation programs for stable CAD patients.

The effect of severe burn injury on vascular health is unknown. We tested the hypothesis that, compared with nonburn control subjects, vasodilator function would be reduced and that pulse-wave velocity (a measure of arterial stiffness) would be increased in individuals with prior burn injuries, the extent of which would be associated with the magnitude of body surface area having sustained a severe burn. Pulse-wave velocity and macrovascular (flow-mediated dilation) and microvascular (reactive hyperemia) dilator functions were assessed in 14 nonburned control subjects and 32 age-matched subjects with well-healed burn injuries. Fifteen subjects with burn injuries covering 17–40% of body surface area were assigned to a moderate burn injury group, and 17 subjects with burn injuries covering >40% of body surface area were assigned to a high burn injury group. Pulse-wave velocity [ P = 0.3 (central) and P = 0.3 (peripheral)] did not differ between the three groups. Macrovascular dilator function was reduced in the moderate ( P = 0.07) and high ( P < 0.05) burn injury groups compared with the control group. Likewise, peak vascular conductance during postocclusive reactive hyperemia differed from the moderate burn injury group ( P = 0.08 vs. control) and the high burn injury group ( P < 0.05 vs. control). These data suggest that vasodilator function is impaired in well-healed burn injury survivors, with the extent of impairment not dependent on the magnitude of body surface area having sustained a severe burn injury.

Heat stress followed by an accompanying hemorrhagic challenge may influence hemostasis. We tested the hypothesis that hemostatic responses would be increased by passive heat stress, as well as exercise-induced heat stress, each with accompanying central hypovolemia to simulate a hemorrhagic insult. In aim 1, subjects were exposed to passive heating or normothermic time control, each followed by progressive lower-body negative pressure (LBNP) to presyncope. In aim 2 subjects exercised in hyperthermic environmental conditions, with and without accompanying dehydration, each also followed by progressive LBNP to presyncope. At baseline, pre-LBNP, and post-LBNP (30)] to 5.1% post-LBNP compared with 1.5% (time control) and 2.7% in N-LBNP ( P = 0.05 for main effect). Hyperthermia also potentiated increased platelet counts post-LBNP as follows: 274 K/µl for H-LBNP, 246 K/µl for N-LBNP, and 196 K/µl for time control ( P < 0.05 for the interaction). For aim 2, hydration status associated with exercise in the heat did not affect the hemostatic activity, but fibrinolysis (LY30) was increased to 6–10% when subjects were dehydrated compared with an increase to 2–4% when hydrated ( P = 0.05 for treatment). Central hypovolemia via LBNP is a primary driver of hemostasis compared with hyperthermia and dehydration effects. However, hyperthermia does induce significant thrombocytosis and by itself causes an increase in clot lysis. Dehydration associated with exercise-induced heat stress increases clot lysis but does not affect exercise-activated or subsequent hypovolemia-activated hemostasis in hyperthermic humans. Clinical implications of these findings are that quickly restoring a hemorrhaging hypovolemic trauma patient with cold noncoagulant fluids (crystalloids) can have serious deleterious effects on the body’s innate ability to form essential clots, and several factors can increase clot lysis, which should therefore be closely monitored.

NEW FINDINGS What is the central question of this study? Does folic acid supplementation alleviate thermoregulatory and cardiovascular strain of older adults during exposure to extreme heat and humidity? What is the main finding and its importance? Folic acid supplementation for 6 weeks did not affect whole-limb blood flow/vasodilatation, core and skin temperatures, heart rate, blood pressure and cardiac output. Thus, 6 weeks of folic acid supplementation does not alleviate thermoregulatory or cardiovascular strain of healthy older adults exposed to extreme heat and humidity. ABSTRACT Folic acid supplementation reverses age-related reductions in cutaneous vasodilatation during passive heating. However, it is unknown if folic acid supplementation alleviates thermoregulatory and cardiovascular strain experienced by older adults during heat exposure. We evaluated the effect of folic acid supplementation on thermoregulatory and cardiovascular responses of nine healthy older adults (61-72 years, 3 males/6 females) exposed to extreme heat and humidity. Participants rested at 42°C while relative humidity was increased from 30% to 70% in 2% increments every 5 min. The protocol was performed before (CON) and after (FOLIC) 6 weeks of folic acid supplementation (5 mg day-1 ). Local cutaneous vascular conductance (CVC, laser-Doppler flowmetry), forearm vascular conductance (FVC, Doppler ultrasound), mean skin and oesophageal temperatures, heart rate, blood pressure and cardiac output were measured. Folic acid supplementation increased fasting serum folate concentrations (P