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Heart rate variability (HRV), defined as the variability between successive heart beats, is a noninvasive measure of autonomic nervous system (ANS) function, which may be altered following traumatic brain injury (TBI). This scoping review summarizes the existing literature regarding changes in HRV after TBI as well as the association between measures of HRV and outcomes following TBI. A literature search for articles assessing 'heart rate variability' and 'brain injury' or 'concussion' was completed. Articles were included if HRV was measured in human subjects with TBI or concussion. Review articles, protocol papers, and studies including non-traumatic injuries were excluded. Sixty-three articles were included in this review. Varied methods were used to measure HRV in the different studies. Forty articles included information about differences in HRV measures after TBI and/or longitudinal changes after TBI. Fifteen studies assessed HRV and symptoms following TBI, and 15 studies assessed HRV and either functional or cognitive outcomes after TBI. HRV has been studied in the context of mortality, clinical symptoms, and medical, functional, or cognitive outcomes following TBI. Methods used to measure HRV have varied amongst the different studies, which may impact findings, standardized protocols are needed for future research. [ABSTRACT FROM AUTHOR]

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

Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signaling, the primary mechanism mediating sympathetic vasoconstriction at sea level (SL), has not been examined at HA. In nine male lowlanders, we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (ΔFVC) during 1) incremental intrα-arterial infusion of phenylephrine to assess α1-adrenergic receptor responsiveness and 2) combined intrα-arterial infusion of β-adrenergic and α-adrenergic antagonists propranolol and phentolamine (α-β-blockade) to assess adrenergic vascular restraint at rest and during exercise-induced sympathoexcitation (cycling; 60% peak power). Experiments were performed near SL (344 m) and after 3 wk at HA (4,383 m). HA abolished the vasoconstrictor response to low-dose phenylephrine (DFVC: SL: -34 ± 15%, vs. HA; þ3 ± 18%; P < 0.0001) and markedly attenuated the response to medium (DFVC: SL: -45 ± 18% vs. HA: -28 ± 11%; P = 0.009) and high (DFVC: SL: -47 ± 20%, vs. HA: -35 ± 20%; P = 0.041) doses. Blockade of β-adrenergic receptors alone had no effect on resting FVC (P = 0.500) and combined α-β-blockade induced a similar vasodilatory response at SL and HA (P = 0.580). Forearm vasoconstriction during cycling was not different at SL and HA (P = 0.999). Interestingly, cycling-induced forearm vasoconstriction was attenuated by α-β-blockade at SL (DFVC: Control: -27 ± 128 vs. α-β-blockade: þ19 ± 23%; P = 0.0004), but unaffected at HA (DFVC: Control: -20 ± 22 vs. α-β-blockade: -23 ± 11%; P = 0.999). Our results indicate that in healthy males, altitude acclimatization attenuates a1-adrenergic receptor responsiveness; however, resting α-adrenergic restraint remains intact, due to concurrent resting sympathoexcitation. Furthermore, forearm vasoconstrictor responses to cycling are preserved, although the contribution of adrenergic receptors is diminished, indicating a reliance on alternative vasoconstrictor mechanisms. [ABSTRACT FROM AUTHOR]

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 ...O2peak), and during maximal exercise on a lower-body cycle ergometer. We compared cardiovascular variables using two-way ANOVA (group x 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 ...O2peak. 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. [ABSTRACT FROM AUTHOR]

Chronic exposure to hypoxia (high-altitude, HA; >4000 m) attenuates the vasodilatory response to exercise and is associated with a persistent increase in basal sympathetic nerve activity (SNA). The mechanism(s) responsible for the reduced vasodilatation and exercise hyperaemia at HA remains unknown. We hypothesized that heightened adrenergic signalling restrains skeletal muscle blood flow during handgrip exercise in lowlanders acclimatizing to HA. We tested nine adult males (n = 9) at sea-level (SL; 344 m) and following 21–28 days at HA (∼4300 m). Forearm blood flow (FBF; duplex ultrasonography), mean arterial pressure (MAP; brachial artery catheter), forearm vascular conductance (FVC; FBF/MAP), and arterial and venous blood sampling (O2 delivery (DO2 ) and uptake (V...O2 )) were measured at rest and during graded rhythmic handgrip exercise (5%, 15% and 25% of maximum voluntary isometric contraction; MVC) before and after local α- and β-adrenergic blockade (intra-arterial phentolamine and propranolol). HA reduced ΔFBF (25% MVC: SL: 138.3 ± 47.6 vs. HA: 113.4 ± 37.1 ml min−1; P = 0.022) and ΔV...O2 (25% MVC: SL: 20.3 ± 7.5 vs. HA: 14.3 ± 6.2 ml min−1; P = 0.014) during exercise. Local adrenoreceptor blockade at HA restored FBF during exercise (25% MVC: SLα–β blockade: 164.1 ± 71.7 vs. HAα–β blockade: 185.4 ± 66.6 ml min−1; P = 0.947) but resulted in an exaggerated relationship between DO2 and V...O2 (DO2 /V...O2 slope: SL: 1.32; HA: slope: 1.86; P = 0.037). These results indicate that tonic adrenergic signalling restrains exercise hyperaemia in lowlanders acclimatizing to HA. The increase in adrenergic restraint is necessary to match oxygen delivery to demand and prevent over perfusion of contracting muscle at HA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Andeans with chronic mountain sickness (CMS) and polycythemia have similar maximal oxygen uptakes to healthy Andeans. Therefore, this study aimed to explore potential adaptations in convective oxygen transport, with a specific focus on sympathetically mediated vasoconstriction of nonactive skeletal muscle. In Andeans with (CMS+, n = 7) and without (CMS-, n = 9) CMS, we measured components of convective oxygen delivery, hemodynamic (arterial blood pressure via intra-arterial catheter), and autonomic responses [muscle sympathetic nerve activity (MSNA)] at rest and during steady-state submaximal cycling exercise [30% and 60% peak power output (PPO) for 5 min each]. Cycling caused similar increases in heart rate, cardiac output, and oxygen delivery at both workloads between both Andean groups. However, at 60% PPO, CMS+ had a blunted reduction in Dtotal peripheral resistance (CMS-, -10.7 ± 3.8 vs. CMS+, -4.9 ± 4.1 mmHg·L-1·min-1; P = 0.012; d = 1.5) that coincided with a greater Dforearm vasoconstriction (CMS-, -0.2 ± 0.6 vs. CMS+, 1.5 ± 1.3 mmHg·mL-1·min-1; P = 0.008; d = 1.7) and a rise in Ddiastolic blood pressure (CMS-, 14.2 ± 7.2 vs. CMS+, 21.6 ± 4.2 mmHg; P = 0.023; d = 1.2) compared with CMS-. Interestingly, although MSNA burst frequency did not change at 30% or 60% of PPO in either group, at 60% Dburst incidence was attenuated in CMS+ (P = 0.028; d = 1.4). These findings indicate that in Andeans with polycythemia, light intensity exercise elicited similar cardiovascular and autonomic responses compared with CMS-. Furthermore, convective oxygen delivery is maintained during moderateintensity exercise despite higher peripheral resistance. In addition, the elevated peripheral resistance during exercise was not mediated by greater sympathetic neural outflow, thus other neural and/or nonneural factors are perhaps involved. [ABSTRACT FROM AUTHOR]

Key points: Humans suffering from polycythaemia undergo multiple circulatory adaptations including changes in blood rheology and structural and functional vascular adaptations to maintain normal blood pressure and vascular shear stresses, despite high blood viscosity.During exercise, several circulatory adaptations are observed, especially involving adrenergic and non‐adrenergic mechanisms within non‐active and active skeletal muscle to maintain exercise capacity, which is not observed in animal models.Despite profound circulatory stress, i.e. polycythaemia, several adaptations can occur to maintain exercise capacity, therefore making early identification of the disease difficult without overt symptomology.Pharmacological treatment of the background heightened sympathetic activity may impair the adaptive sympathetic response needed to match local oxygen delivery to active skeletal muscle oxygen demand and therefore inadvertently impair exercise capacity. Excessive haematocrit and blood viscosity can increase blood pressure, cardiac work and reduce aerobic capacity. However, past clinical investigations have demonstrated that certain human high‐altitude populations suffering from excessive erythrocytosis, Andeans with chronic mountain sickness, appear to have phenotypically adapted to life with polycythaemia, as their exercise capacity is comparable to healthy Andeans and even with sea‐level inhabitants residing at high altitude. By studying this unique population, which has adapted through natural selection, this study aimed to describe how humans can adapt to life with polycythaemia. Experimental studies included Andeans with (n = 19) and without (n = 17) chronic mountain sickness, documenting exercise capacity and characterizing the transport of oxygen through blood rheology, including haemoglobin mass, blood and plasma volume and blood viscosity, cardiac output, blood pressure and changes in total and local vascular resistances through pharmacological dissection of α‐adrenergic signalling pathways within non‐active and active skeletal muscle. At rest, Andeans with chronic mountain sickness had a substantial plasma volume contraction, which alongside a higher red blood cell volume, caused an increase in blood viscosity yet similar total blood volume. Moreover, both morphological and functional alterations in the periphery normalized vascular shear stress and blood pressure despite high sympathetic nerve activity. During exercise, blood pressure, cardiac work and global oxygen delivery increased similar to healthy Andeans but were sustained by modifications in both non‐active and active skeletal muscle vascular function. These findings highlight widespread physiological adaptations that can occur in response to polycythaemia, which allow the maintenance of exercise capacity. Key points: Humans suffering from polycythaemia undergo multiple circulatory adaptations including changes in blood rheology and structural and functional vascular adaptations to maintain normal blood pressure and vascular shear stresses, despite high blood viscosity.During exercise, several circulatory adaptations are observed, especially involving adrenergic and non‐adrenergic mechanisms within non‐active and active skeletal muscle to maintain exercise capacity, which is not observed in animal models.Despite profound circulatory stress, i.e. polycythaemia, several adaptations can occur to maintain exercise capacity, therefore making early identification of the disease difficult without overt symptomology.Pharmacological treatment of the background heightened sympathetic activity may impair the adaptive sympathetic response needed to match local oxygen delivery to active skeletal muscle oxygen demand and therefore inadvertently impair exercise capacity. [ABSTRACT FROM AUTHOR]

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. 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. 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 FROM AUTHOR]

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. 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. 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 FROM AUTHOR]

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. 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. [ABSTRACT FROM AUTHOR]

Sympathetic vasoconstriction is mediated by α-adrenergic receptors under resting conditions. During exercise, increased sympathetic nerve activity (SNA) is directed to inactive and active skeletal muscle; however, it is unclear what mechanism(s) are responsible for vasoconstriction during large muscle mass exercise in humans. The aim of this study was to determine the contribution of α-adrenergic receptors to sympathetic restraint of inactive skeletal muscle and active skeletal muscle during cycle exercise in healthy humans. In ten male participants (18-35 yr), mean arterial pressure (intra-arterial catheter) and forearm vascular resistance (FVR) and conductance (FVC) were assessed during cycle exercise (60% total peak workload) alone and during combined cycle exercise + handgrip exercise (HGE) before and after intra-arterial blockade of α- and β-adrenoreceptors via phentolamine and propranolol, respectively. Cycle exercise caused vasoconstriction in the inactive forearm that was attenuated ~80% with adrenoreceptor blockade (%ΔFVR, +81.7 ± 84.6 vs. +9.7 ± 30.7%; P = 0.05). When HGE was performed during cycle exercise, the vasodilatory response to HGE was restrained by ~40% (ΔFVC HGE, +139.3 ± 67.0 vs. cycle exercise: +81.9 ± 66.3 ml·min-1·100 mmHg-1; P = 0.03); however, the restraint of active skeletal muscle blood flow was not due to α-adrenergic signaling. These findings highlight that α-adrenergic receptors are the primary, but not the exclusive mechanism by which sympathetic vasoconstriction occurs in inactive and active skeletal muscle during exercise. Metabolic activity or higher sympathetic firing frequencies may alter the contribution of α-adrenergic receptors to sympathetic vasoconstriction. Finally, nonadrenergic vasoconstrictor mechanisms may be important for understanding the regulation of blood flow during exercise. NEW & NOTEWORTHY Sympathetic restraint of vascular conductance to inactive skeletal muscle is critical to maintain blood pressure during moderate- to high-intensity whole body exercise. This investigation shows that cycle exercise-induced restraint of inactive skeletal muscle vascular conductance occurs primarily because of activation of α-adrenergic receptors. Furthermore, exercise-induced vasoconstriction restrains the subsequent vasodilatory response to hand-grip exercise; however, the restraint of active skeletal muscle vasodilation was in part due to nonadrenergic mechanisms. We conclude that α-adrenergic receptors are the primary but not exclusive mechanism by which sympathetic vasoconstriction restrains blood flow in humans during whole body exercise and that metabolic activity modulates the contribution of α-adrenergic receptors. [ABSTRACT FROM AUTHOR]

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% 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 on 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 versus Control (P < 0.01). However, at 25°C, core temperature responses were not different versus 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Although the severity of a burn injury is often associated with the percentage of total body surface area burned (%TBSA), the thermoregulatory consequences of a given %TBSA injury do not account for the interactive effects of body morphology and metabolic heat production (H prod). Purpose: Using a simulated burn injury model to mimic the detrimental effect of a 40% TBSA injury on whole-body evaporative heat dissipation, core temperature response to exercise in physiologically uncompensable conditions between morphologically disparate groups were examined at (i) an absolute H prod (W), and (ii) a mass-specific H prod (W·kg−1). Methods: Healthy, young, nonburned individuals of small (SM, n = 11) or large (LG, n = 11) body size cycled for 60 min at 500 W or 5.3 W·kg−1 of H prod in 39°C and 20% relative humidity conditions. A 40% burn injury was simulated by affixing a highly absorbent, vapor-impermeable material across the torso (20% TBSA), arms (10% TBSA), and legs (10% TBSA) to impede evaporative heat loss in those regions. Results: Although the elevation in core temperature was greater in SM compared with LG at an H prod of 500 W (SM, 1.69°C ± 0.26°C; LG, 1.05°C ± 0.26°C; P < 0.01), elevations in core temperature were not different at an H prod of 5.3 W·kg−1 between groups (SM, 0.99°C ± 0.32°C; LG, 1.05°C ± 0.26°C; P = 0.66). Conclusions: These data suggest that among individuals with a 40% TBSA burn injury, a smaller body size leads to exacerbated elevations in core temperature during physical activities eliciting the same absolute H prod (non–weight-bearing tasks) but not activities eliciting the same mass-specific H prod (weight-bearing tasks). [ABSTRACT FROM AUTHOR]

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; WETFAN). 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 WETFAN from 30 to 90 min (P = 0.05). Evaporative mass losses (inclusive of sweat and water losses from the shirt) were greatest in WETFAN, followed by WET, and then DRY (P = 0.01). Sweat losses were lowest in WET, followed by DRY, and then WETFAN (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 watersoaked 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. [ABSTRACT FROM AUTHOR]

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 (VO2max) 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 VO2max 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 VO2max in individuals with burn injuries and that the magnitude of body surface area burned does not lessen this adaptive response. [ABSTRACT FROM AUTHOR]

Objective: To examine heart rate variability (HRV) at rest and with a 2-Back cognitive task involving executive function and sustained attention in athletes during the acute phase following concussion and compare them with the controls. Participants: Twenty-three male and female collegiate athletes (20 ± 1 years) following (4 ± 1 days) a sports-related concussion and 23 sports- and sex-matched noninjured controls. Procedure: Continuous R-R interval was acquired using 3-lead electrocardiogram for 3 minutes each at rest and during the 2-Back task. HRV was quantified as percent high-frequency (HF) power. Results: At rest, lower percent HF power was observed in the concussed athletes (23 ± 11) compared with the controls (38 ± 14; F= .0027). However, with the 2-Back task, an increase in HF power was observed in the concussed group (39 ± 12; P = .0008) from rest and was comparable with the controls (36 ± 15). No difference in HF power between rest and 2-Back task was observed in the controls. Conclusion; Lower HRV was observed at rest following concussion. An increase in HRV, suggestive of enhanced prefrontal cortex (PFC) functioning, was observed during a cognitive task in the concussed athletes. Therefore, cognitive tasks as early as 4 days after injury may increase PFC functioning from rest and expedite return to learn in collegiate athletes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study? Does inspiratory resistance breathing improve tolerance to simulated haemorrhage in individuals with elevated internal temperatures? What is the main finding and its importance? The main finding of this study is that inspiratory resistance breathing modestly improves tolerance to a simulated progressive haemorrhagic challenge during heat stress. These findings demonstrate a scenario in which exploitation of the respiratory pump can ameliorate serious conditions related to systemic hypotension. Abstract: Heat exposure impairs human blood pressure control and markedly reduces tolerance to a simulated haemorrhagic challenge. Inspiratory resistance breathing enhances blood pressure control and improves tolerance during simulated haemorrhage in normothermic individuals. However, it is unknown whether similar improvements occur with this manoeuvre in heat stress conditions. In this study, we tested the hypothesis that inspiratory resistance breathing improves tolerance to simulated haemorrhage in individuals with elevated internal temperatures. On two separate days, eight subjects performed a simulated haemorrhage challenge [lower‐body negative pressure (LBNP)] to presyncope after an increase in internal temperature of 1.3 ± 0.1°C. During one trial, subjects breathed through an inspiratory impedance device set at 0 cmH2O of resistance (Sham), whereas on a subsequent day the device was set at −7 cmH2O of resistance (ITD). Tolerance was quantified as the cumulative stress index. Subjects were more tolerant to the LBNP challenge during the ITD protocol, as indicated by a > 30% larger cumulative stress index (Sham, 520 ± 306 mmHg min; ITD, 682 ± 324 mmHg min; P < 0.01). These data indicate that inspiratory resistance breathing modestly improves tolerance to a simulated progressive haemorrhagic challenge during heat stress. [ABSTRACT FROM AUTHOR]

Key points: The arterial baroreflex's operating point pressure is reset upwards and rightwards from rest in direct relation to the increases in dynamic exercise intensity. The intraneural pathways and signalling mechanisms that lead to upwards and rightwards resetting of the operating point pressure, and hence the increases in central sympathetic outflow during exercise, remain to be identified. We tested the hypothesis that the central production of angiotensin II during dynamic exercise mediates the increases in sympathetic outflow and, therefore, the arterial baroreflex operating point pressure resetting during acute and prolonged dynamic exercise. The results identify that perindopril, a centrally acting angiotensin converting enzyme inhibitor, markedly attenuates the central sympathetic outflow during acute and prolonged dynamic exercise. Abstract: We tested the hypothesis that the signalling mechanisms associated with the dynamic exercise intensity related increases in muscle sympathetic nerve activity (MSNA) and arterial baroreflex resetting during exercise are located within the central nervous system. Participants performed three randomly ordered trials of 70° upright back‐supported dynamic leg cycling after ingestion of placebo and two different lipid soluble angiotensin converting enzyme inhibitors (ACEi): perindopril (high lipid solubility), captopril (low lipid solubility). Repeated measurements of whole venous blood (n = 8), MSNA (n = 7) and arterial blood pressures (n = 14) were obtained at rest and during an acute (SS1) and prolonged (SS2) bout of steady state dynamic exercise. Arterial baroreflex function curves were modelled at rest and during exercise. Peripheral venous superoxide concentrations measured by electron spin resonance spectroscopy were elevated during exercise and were not altered by ACEi at rest (P ≥ 0.4) or during exercise (P ≥ 0.3). Baseline MSNA and mean arterial pressure were unchanged at rest (P ≥ 0.1; P ≥ 0.8, respectively). However, during both SS1 and SS2, the centrally acting ACEi perindopril attenuated MSNA compared to captopril and the placebo (P < 0.05). Arterial pressures at the operating point and threshold pressures were decreased with perindopril from baseline to SS1 with no further changes in the operating point pressure during SS2 under all three conditions. These data suggest that centrally acting ACEi is significantly more effective at attenuating the increase in the acute and prolonged exercise‐induced increases in MSNA. [ABSTRACT FROM AUTHOR]

The effect of acute increases in cardiac contractility on cerebral blood flow (CBF) remains unknown. We hypothesized that the external carotid artery (ECA) downstream vasculature modifies the direct influence of acute increases in heart rate and cardiac function on CBF regulation. Twelve healthy subjects received two infusions of dobutamine [first a low dose (5 µg·kg-1·min-1) and then a high dose (15 µg·kg-1·min-1)] for 12 min each. Cardiac output, blood flow through the internal carotid artery (ICA) and ECA, and echocardiographic measurements were performed during dobutamine infusions. Despite increases in cardiac contractility, cardiac output, and arterial pressure with dobutamine, ICA blood flow and conductance slightly decreased from resting baseline during both low- and high-dose infusions. In contrast, ECA blood flow and conductance increased appreciably during both low- and high-dose infusions. Greater ECA vascular conductance and corresponding increases in blood flow may protect overperfusion of intracranial cerebral arteries during enhanced cardiac contractility and associated increases in cardiac output and perfusion pressure. Importantly, these findings suggest that the acute increase of blood perfusion attributable to dobutamine administration does not cause cerebral overperfusion or an associated risk of cerebral vascular damage. [ABSTRACT FROM AUTHOR]