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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]

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]

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

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. [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]

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]

The US 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% 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 noninjured sites demonstrate similar elevations in skin blood flow and sweating during exercise-induced hyperthermia. Methods: Twenty burn survivors (>1 yr postinjury; four females) cycled for 60 min in a 39.7°C ± 0.3°C and 21.1% ± 3.3% relative humidity environment at approximately 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 (LDFDON) and adjacent noninjured control (LDFCON) sites. At 45 min of exercise, local sweat rates (Technical Absorbents) were measured within the same donor (LSRDON) and noninjured (LSRCON) areas. Results: After 60 min of exercise, core and skin temperatures reached 38.2°C ± 0.4°C and 35.5°C ± 1.2°C, respectively. The increase in skin blood flow from baseline to end-exercise (LDFDON, 91.6 ± 44.5 AU; LDFCON, 106.0 ± 61.6 AU; P = 0.17) and local sweat rates (LSRDON, 0.46 ± 0.26 mg·cm−2·min−1; LSRCON, 0.53 ± 0.25 mg·cm−2·min−1; P = 0.14) were not different between donor and noninjured control sites. Conclusions: 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. [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]

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]

New Findings What is the central question of this study? This study evaluated the following central question: does N-acetylcysteine (N-AC), an antioxidant that readily penetrates the blood-brain barrier, have the capability to reduce the increase in sympathetic nerve activity observed during hyperacute intermittent hypoxia?, What is the main finding and its importance? We demonstrate that N-AC decreases muscle sympathetic nerve activity in response to hyperacute intermittent hypoxia versus placebo control. This finding suggests that antioxidants, such as N-AC, have therapeutic potential in obstructive sleep apnoea., This investigation tested the following hypotheses: that (i) N-acetylcysteine (N-AC) attenuates hyperacute intermittent hypoxia-induced sympathoexcitation, (ii) without elevating superoxide measured in peripheral venous blood. Twenty-eight healthy human subjects were recruited to the study. One hour before experimentation, each subject randomly ingested either 70 mg kg−1 of N-AC ( n = 16) or vehicle placebo ( n = 12). Three-lead ECG and arterial blood pressure, muscle sympathetic nerve activity ( n = 17) and whole-blood superoxide concentration (using electron paramagnetic resonance spectroscopy; n = 12) were measured. Subjects underwent a 20 min hyperacute intermittent hypoxia training (hAIHT) protocol that consisted of cyclical end-expiratory apnoeas with 100% nitrogen. N-AC decreased muscle sympathetic nerve activity after hAIHT compared with placebo ( P < 0.02). However, N-AC did not alter superoxide concentrations in venous blood compared with placebo ( P > 0.05). Moreover, hAIHT did not increase superoxide concentrations in the peripheral circulation as measured by electron paramagnetic resonance ( P > 0.05). Based on these findings, we contend that (i) hAIHT and (ii) the actions of N-AC in hAIHT are primarily mediated centrally rather than peripherally, although central measurements of reactive oxygen species are difficult to obtain in human subjects, thus making this assertion difficult to verify. This investigation suggests the possibility of developing a pharmaceutical therapy to inhibit the sympathoexcitation associated with obstructive sleep apnoea. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary function is lower after a severe burn injury, which could influence ventilatory responses during exercise. It is unclear whether exercise training improves pulmonary function or ventilatory responses during exercise in adults with well-healed burn injuries. Therefore, we tested the hypothesis that exercise training improves pulmonary function and ventilatory responses during exercise in adults with well-healed burn injuries. Methods: Thirty-nine adults (28 with well-healed burn injuries and 11 non–burn-injured controls) completed 6 months of unsupervised, progressive exercise training including endurance, resistance, and high-intensity interval components. Before and after exercise training, we performed comprehensive pulmonary function testing and measured ventilatory responses during cycling exercise. We compared variables using two-way ANOVA (group–time; i.e., preexercise/postexercise training (repeated factor)). Results: Exercise training did not increase percent predicted spirometry, lung diffusing capacity, or airway resistance measures (time: P ≥ 0.14 for all variables). However, exercise training reduced minute ventilation (V̇ E; time: P ≤ 0.05 for 50 and 75 W) and the ventilatory equivalent for oxygen (V̇ E/V̇O2; time: P < 0.001 for 75 W) during fixed-load exercise for both groups. The ventilatory equivalent for carbon dioxide (V̇ E/V̇CO2) during exercise at 75 W was reduced after exercise training (time: P = 0.04). The percentage of age-predicted maximum heart rate at the ventilatory threshold was lower in adults with well-healed burn injuries before (P = 0.002), but not after (P = 0.22), exercise training. Lastly, exercise training increased V̇ E and reduced V̇ E/V̇O2 during maximal exercise (time: P = 0.005 for both variables). Conclusions: These novel findings demonstrate that exercise training can improve ventilatory responses during exercise in adults with well-healed burn injuries. [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]

R2278 --> Introduction: Populations suffering from polycythemia such as polycythemia vera, Chuvash polycythemia, and chronic mountain sickness (CMS) suffer exercise fatigue and reduced exercise capacity. Potential mechanisms for reduced exercise capacity include the negative influences of high hematocrit, elevated blood viscosity, and increased sympathetic activity on convective and diffusive oxygen transport. However, it remains unclear how sympathetic activity impacts blood flow during isolated forearm exercise in Andeans suffering with polycythemia. Purpose: Therefore, using the isolated forearm handgrip model, the present study sought to examine the role of α‐adrenergic vasoconstrictor signaling in regulating skeletal muscle vasodilator function in seven Andeans with polycythemia (CMS+; n=7) and nine of their healthy townsmen (CMS‐; n=9) living at ~4350m. Methods: Forearm blood flow (FBF; Doppler ultrasound), mean arterial pressure (MAP, intra‐arterial catheter), and changes in forearm vascular conductance (∆FVC), calculated via FBF and MAP, were measured at rest and during graded handgrip exercise (HGE; 5, 15, 25% maximal voluntary contraction; MVC), before and after local +α‐β adrenergic blockade (phentolamine; propranolol). Blood samples were taken via arterial and venous catheter at rest and each stage of handgrip exercise to determine oxygen delivery, uptake, and extraction. All data are quantified as mean±SD. Results: During the control trial, progressive HGE increased FVC (CMS‐: P<0.01; CMS+: P<0.01), oxygen delivery (CMS‐: P<0.01; CMS+: P<0.01) and extraction (CMS‐: P<0.01; CMS+: P<0.01) similarly in both CMS‐ and CMS+ Andeans. However, after +α‐β adrenergic blockade, the FVC response to HGE at 25% was greater in CMS+ (∆FVC: control: 92.8±31.1 vs. +α‐β blockade: 137.5±66.7 ml·min‐1·100mmHg‐1; P<0.01) whereas the FVC response remained unchanged in CMS‐ (∆FVC: control: 109.0±32.8 vs. +α‐β blockade: 95.5±57.9 ml·min‐1·100mmHg‐1; P=0.15). In CMS+, increased FVC during +α‐β adrenergic blockade also increased oxygen delivery during 25% HGE (∆DO2: control: 21.9±5.9 vs. +α‐β blockade: 29.7±9.9 ml·min‐1; P<0.01); however, oxygen extraction remained unchanged (∆a‐VO2: control: 9.6±4.7 vs. +α‐β blockade: 8.3±4.1 ml·dl‐1; P=0.46). Conclusion: CMS+ individuals demonstrate heightened α‐adrenergic restraint of vasodilation during HGE. However, oxygen uptake in the forearm during exercise remains intact due to elevated arterial oxygen content from increased hemoglobin. Perhaps, a phenotypical trade‐off to polycythemia; whereby heightened vasoconstrictor signaling restrains blood flow to match the needed metabolic demand, or elevated whole blood viscosity elicits greater shear signaling requiring higher sympathetic restraint. [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]

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]

The U.S. Department of Defense's Medical Standards for Appointment, Enlistment, or Induction into the Military Services excludes personnel with burn injuries covering 18% or more of their body surface area (BSA). However, this requirement does not consider the metabolic heat loads associated with physical activities of different intensities that may influence a burn survivor's ability to perform his/her duties. Purpose: This study aimed to test the hypothesis that the elevation in internal body temperature during exercise in a hot environment is influenced by the combination of exercise intensity and BSA burned. Methods: Ten healthy participants (8 males, 2 females; 32 ± 9 yr; 75.3 ± 11.7 kg) completed eight exercise trials on a cycle ergometer, each with different combinations of metabolic heat productions (low, 4 W·kg−1; moderate, 6 W·kg−1) and simulated BSA burn in a hot environmental chamber (39.9°C ± 0.3°C, 20.1% ± 1.5% RH). Burns were simulated by covering 0%, 20%, 40%, or 60% of participants' BSA with a highly absorbent, vapor-impermeable material. Gastrointestinal temperature (T GI) was recorded, with the primary analysis being the increase in T GI after 60 min of exercise. Results: We identified an interaction effect for the increase in T GI (P < 0.01), suggesting T GI was influenced by both intensity and simulated burn BSA. Regardless of the percentage BSA burn simulated, the increase in T GI was similar across low-intensity trials (0.70°C ± 0.26°C, P > 0.11 for all). However, during moderate-intensity exercise, the increase in T GI was greater for the 60% (1.78°C ± 0.38°C, P < 0.01) and 40% BSA coverage trials (1.33°C ± 0.44°C, P = 0.04), relative to 0% (0.82°C ± 0.36°C). There were no differences in T GI responses between 0% and 20% trials. Conclusion: These data suggest that exercise intensity influences the relationship between burn injury size and thermoregulatory responses in a hot environment. [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]

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]

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

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]

R5149 --> 555.26 --> Recently, it has been identified that volitionally initiated finger tapping, which is a "very light motor effort" physical activity, elicits greater increases in mean anterior cerebral artery blood velocity (ACAmean), ACA vascular conductance index (ACAvci) and prefrontal oxygenation (Oxy‐Hb) responses compared to a cued start. These findings suggest that differences in ACAmean and prefrontal Oxy‐Hb responses between the exercise initiation modes may be related to central command. However, it remains unknown if similar responses are observed at the onset of voluntary exercise of a "moderate motor effort". Therefore, the purpose of this study was to determine ACAmean, ACAvci and prefrontal Oxy‐Hb responses during dynamic hand grip exercise at 40% of maximal voluntary contraction (MVC) during two exercise initiation modes (voluntary or cued start). ACAmean, ACAvci, and prefrontal Oxy‐Hb were measured in seven participants (4 females and 3 males; aged 26 ± 3 years) at baseline (‐30 sec to ‐20 sec prior to initiation of exercise), pre‐exercise (‐20 sec to 0 sec) and the onset of exercise (0 sec to 15 sec) of each exercise initiation condition. Participants perceived exertion Borg Scale rating for the 40%‐MVC was 11.5 (median). A two‐way repeated measures ANOVA was conducted for the variables of interests. A significant factor interactions was identified for ACAmean ((F(2,12) = 5.02, p=0.03)) and Oxy‐Hb ((F(2,12) = 5.86, p= 0.02)). Post hoc test revealed that a voluntary start to hand grip exercise increased ACAmean by 2.6±1.0 cm/s (p=0.002) v.s. 0.7± 2.0 cm/s for a cued start (p=0.3) and increased Oxy‐Hb by 11.6±10.7 µM (p=0.02) v.s. 2.9±9.5 µM for a cued start (p=0.7) at the onset of exercise when compared to baseline. Furthermore, there was tendency in ACAvci to also increase with voluntary start by 3.9%±6.0 (p=0.06) vs. cued start 0.43% ± 6.0 p=0.57 from baseline to the initial onset of exercise. These primary findings suggest that moderate dynamic hand grip exercise elicits similar anterior cerebral blood flow and prefrontal oxygenation responses previously observed and thus, showing similar metabolic demands as finger‐tapping. [ABSTRACT FROM AUTHOR]