Acute sympathetic activation blunts the hyperemic and vasodilatory response to passive leg movement.

Heightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) has not been adequately addressed. This study sought to test the hypothesis that elevated MSNA diminishes the vasodilatory response to PLM in healthy young males (n = 11, 25 ± 2 year). Post exercise circulatory occlusion (PECO) following 2 min of isometric handgrip (HG) exercise performed at 25% (ExPECO 25%) and 40% (ExPECO 40%) of maximum voluntary contraction was used to incrementally engage the metaboreceptors and augment MSNA. Control trials were performed without PECO (ExCON 25% and ExCON 40%) to account for changes due to HG exercise. PLM was performed 2 min after the cessation of exercise and central and peripheral hemodynamics were assessed. MSNA was directly recorded by microneurography in the peroneal nerve (n = 8). Measures of MSNA (i.e., burst incidences) increased during ExPECO 25% (+ 15 ± 5 burst/100 bpm) and ExPECO 40% (+ 22 ± 4 burst/100 bpm) and returned to pre-HG levels during ExCON trials. Vasodilation, assessed by the change in leg vascular conductance during PLM, was reduced by 16% and 44% during ExPECO 25% and ExPECO 40%, respectively. These findings indicate that elevated MSNA attenuates the vasodilatory response to PLM and that the magnitude of reduction in vasodilation during PLM is graded in relation to the degree of sympathoexcitation.

The impact of obesity on the regulation of muscle blood flow during exercise in patients with heart failure with a preserved ejection fraction.

Obesity is now considered a primary comorbidity in heart failure with preserved ejection fraction (HFpEF) pathophysiology, mediated largely by systemic inflammation. Although there is accumulating evidence for a disease-related dysregulation of blood flow during exercise in this patient group, the role of obesity in the hemodynamic response to exercise remains largely unknown. Small muscle mass handgrip (HG) exercise was used to evaluate exercising muscle blood flow in nonobese (BMI < 30 kg/m2, n = 14) and obese (BMI > 30 kg/m2, n = 40) patients with HFpEF. Heart rate (HR), stroke index (SI), cardiac index (CI), mean arterial pressure (MAP), forearm blood flow (FBF), and vascular conductance (FVC) were assessed during progressive intermittent HG exercise [15%-30%-45% maximal voluntary contraction (MVC)]. Blood biomarkers of inflammation [C-reactive protein (CRP) and interleukin-6 (IL-6)] were also determined. Exercising FBF was reduced in obese patients with HFpEF at all work rates (15%: 304 ± 42 vs. 229 ± 15 mL/min; 30%: 402 ± 46 vs. 300 ± 18 mL/min; 45%: 484 ± 55 vs. 380 ± 23 mL/min, nonobese vs. obese, P = 0.025), and was negatively correlated with BMI (R = -0.47, P < 0.01). In contrast, no differences in central hemodynamics (HR, SI, CI, and MAP) were found between groups. Proinflammatory biomarkers were markedly elevated in patients with obesity (CRP: 2,133 ± 418 vs. 4,630 ± 590 ng/mL, P = 0.02; IL-6: 2.9 ± 0.3 vs. 5.2 ± 0.7 pg/mL, nonobese vs. obese, P = 0.04), and both biomarkers were positively correlated with BMI (CRP: R = 0.40, P = 0.03; IL-6: R = 0.57, P < 0.01). Together, these findings demonstrate the presence of obesity and an accompanying milieu of systemic inflammation as important factors in the dysregulation of exercising muscle blood flow in patients with HFpEF.NEW & NOTEWORTHY Obesity is the primary comorbid condition in HFpEF pathophysiology, but the role of adiposity on the peripheral circulation is not well understood. The present study identified a 30%-40% reduction in forearm blood flow during handgrip exercise, accompanied by a marked elevation in proinflammatory plasma biomarkers, in obese patients with HFpEF compared with their nonobese counterparts. These findings suggest an exaggerated dysregulation in exercising muscle blood flow associated with the obese HFpEF phenotype.

Locomotor Muscle Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction.

[Figure: see text].

Cardiovascular responses to rhythmic handgrip exercise in heart failure with preserved ejection fraction.

Although the contribution of noncardiac complications to the pathophysiology of heart failure with preserved ejection fraction (HFpEF) have been increasingly recognized, disease-related changes in peripheral vascular control remain poorly understood. We utilized small muscle mass handgrip exercise to concomitantly evaluate exercising muscle blood flow and conduit vessel endothelium-dependent vasodilation in individuals with HFpEF (n = 25) compared with hypertensive controls (HTN) (n = 25). Heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), brachial artery blood velocity, and brachial artery diameter were assessed during progressive intermittent handgrip (HG) exercise [15-30-45% maximal voluntary contraction (MVC)]. Forearm blood flow (FBF) and vascular conductance (FVC) were determined to quantify the peripheral hemodynamic response to HG exercise, and changes in brachial artery diameter were evaluated to assess endothelium-dependent vasodilation. HR, SV, and CO were not different between groups across exercise intensities. However, although FBF was not different between groups at the lowest exercise intensity, FBF was significantly lower (20-40%) in individuals with HFpEF at the two higher exercise intensities (30% MVC: 229 ± 8 versus 274 ± 23 ml/min; 45% MVC: 283 ± 17 versus 399 ± 34 ml/min, HFpEF versus HTN). FVC was not different between groups at 15 and 30% MVC but was ∼20% lower in HFpEF at the highest exercise intensity. Brachial artery diameter increased across exercise intensities in both HFpEF and HTN, with no difference between groups. These findings demonstrate an attenuation in muscle blood flow during exercise in HFpEF in the absence of disease-related changes in central hemodynamics or endothelial function.NEW & NOTEWORTHY The current study identified, for the first time, an attenuation in exercising muscle blood flow during handgrip exercise in individuals with heart failure with preserved ejection fraction (HFpEF) compared with overweight individuals with hypertension, two of the most common comorbidities associated with HFpEF. These decrements in exercise hyperemia cannot be attributed to disease-related changes in central hemodynamics or endothelial function, providing additional evidence for disease-related vascular dysregulation, which may be a predominant contributor to exercise intolerance in individuals with HFpEF.

α-Adrenergic receptor regulation of skeletal muscle blood flow during exercise in heart failure patients with reduced ejection fraction.

Patients suffering from heart failure with reduced ejection fraction (HFrEF) experience impaired limb blood flow during exercise, which may be due to a disease-related increase in α-adrenergic receptor vasoconstriction. Thus, in eight patients with HFrEF (63 ± 4 yr) and eight well-matched controls (63 ± 2 yr), we examined changes in leg blood flow (Doppler ultrasound) during intra-arterial infusion of phenylephrine (PE; an α1-adrenergic receptor agonist) and phentolamine (Phen; a nonspecific α-adrenergic receptor antagonist) at rest and during dynamic single-leg knee-extensor exercise (0, 5, and 10 W). At rest, the PE-induced reduction in blood flow was significantly attenuated in patients with HFrEF (-15 ± 7%) compared with controls (-36 ± 5%). During exercise, the controls exhibited a blunted reduction in blood flow induced by PE (-12 ± 4, -10 ± 4, and -9 ± 2% at 0, 5, and 10 W, respectively) compared with rest, while the PE-induced change in blood flow was unchanged compared with rest in the HFrEF group (-8 ± 5, -10 ± 3, and -14 ± 3%, respectively). Phen administration increased leg blood flow to a greater extent in the HFrEF group at rest (+178 ± 34% vs. +114 ± 28%, HFrEF vs. control) and during exercise (36 ± 6, 37 ± 7, and 39 ± 6% vs. 13 ± 3, 14 ± 1, and 8 ± 3% at 0, 5, and 10 W, respectively, in HFrEF vs. control). Together, these findings imply that a HFrEF-related increase in α-adrenergic vasoconstriction restrains exercising skeletal muscle blood flow, potentially contributing to diminished exercise capacity in this population.

Metaboreceptor activation in heart failure with reduced ejection fraction: Linking cardiac and peripheral vascular haemodynamics.

NEW FINDINGS: What is the central question of this research? Do patients with heart failure with reduced ejection fraction (HFrEF) exhibit a greater dependence on cardiac or peripheral vascular haemodynamics across multiple levels of muscle metaboreflex activation provoked by postexercise circulatory occlusion? What is the main finding and its importance? The metaboreflex-induced pressor response in HFrEF patients is governed almost entirely by the peripheral circulation, which places a substantial haemodynamic load on the failing heart. This maladaptive response exacerbates the disease-related impairment of systolic function that is a hallmark feature of HFrEF and may therefore contribute to exercise intolerance in this patient group. ABSTRACT: We sought to evaluate the muscle metaboreflex in heart failure with reduced ejection fraction (HFrEF) patients, with an emphasis on the interaction between cardiac and peripheral vascular haemodynamics across multiple levels of metaboreceptor activation. In 23 HFrEF patients (63 ± 2 years of age) and 15 healthy control subjects (64 ± 3 years of age), we examined changes in mean arterial pressure, cardiac output, systemic vascular conductance, effective arterial elastance, stroke work and forearm deoxyhaemoglobin concentration during metaboreceptor activation elicited by postexercise circulatory occlusion (PECO) after three levels of static-intermittent handgrip exercise (15, 30 and 45% maximal voluntary contraction). Across workloads, the metaboreflex-induced increase in deoxyhaemoglobin and mean arterial pressure were similar between groups. However, in control subjects, the pressor response was driven by changes (Δ) in cardiac output  (Δ495 ± 155, Δ564 ± 156 and Δ666 ± 217 ml min-1 ), whereas this change was accomplished by intensity-dependent reductions in systemic vascular conductance in patients with HFrEF (Δ-4.9 ± 1.5, Δ-9.1 ± 1.9 and Δ-12.7 ± 1.8 ml min mmHg-1 ). This differential response contributed to the exaggerated increases in effective arterial elastance in HFrEF patients compared with control subjects, coupled with a blunted response in stroke work in the HFrEF patients. Together, these findings indicate a preserved role of the metaboreflex-induced pressor response in HFrEF but suggest that this response is governed by changes in the peripheral circulation. The net effect of this response appears to be maladaptive, as it places a substantial haemodynamic load on the left ventricle that may exacerbate left ventricular systolic dysfunction and contribute to exercise intolerance in this patient population.

Impaired skeletal muscle vasodilation during exercise in heart failure with preserved ejection fraction.

BACKGROUND: Exercise intolerance is a hallmark symptom of heart failure patients with preserved ejection fraction (HFpEF), which may be related to an impaired ability to appropriately increase blood flow to the exercising muscle. METHODS: We evaluated leg blood flow (LBF, ultrasound Doppler), heart rate (HR), stroke volume (SV), cardiac output (CO), and mean arterial blood pressure (MAP, photoplethysmography) during dynamic, single leg knee-extensor (KE) exercise in HFpEF patients (n=21; 68 ± 2 yrs) and healthy controls (n=20; 71 ± 2 yrs). RESULTS: HFpEF patients exhibited a marked attrition during KE exercise, with only 60% able to complete the exercise protocol. In participants who completed all exercise intensities (0-5-10-15 W; HFpEF, n=13; Controls, n=16), LBF was not different at 0 W and 5 W, but was 15-25% lower in HFpEF compared to controls at 10 W and 15 W (P<0.001). Likewise, leg vascular conductance (LVC), an index of vasodilation, was not different at 0 W and 5 W, but was 15-20% lower in HFpEF compared to controls at 10 W and 15 W (P<0.05). In contrast to these peripheral deficits, exercise-induced changes in central variables (HR, SV, CO), as well as MAP, were similar between groups. CONCLUSIONS: These data reveal a marked reduction in LBF and LVC in HFpEF patients during exercise that cannot be attributed to a disease-related alteration in central hemodynamics, suggesting that impaired vasodilation in the exercising skeletal muscle vasculature may play a key role in the exercise intolerance associated with this patient population.

Evidence of microvascular dysfunction in heart failure with preserved ejection fraction.

OBJECTIVE: While vascular dysfunction is well defined in patients with heart failure (HF) with reduced ejection fraction (HFrEF), disease-related alterations in the peripheral vasculature of patients with HF with preserved ejection fraction (HFpEF) are not well characterised. Thus, we sought to test the hypothesis that patients with HFpEF would demonstrate reduced vascular function, at the conduit artery and microvascular levels, compared with controls. METHODS: We examined conduit artery function via brachial artery flow-mediated dilation (FMD) and microvascular function via reactive hyperaemia (RH) following 5 min of ischaemia in 24 patients with Class II-IV HFpEF and 24 healthy controls matched for age, sex and brachial artery diameter. RESULTS: FMD was reduced in patients with HFpEF compared with controls (HFpEF: 3.1±0.7%; CONTROLS: 5.1±0.5%, p=0.03). However, shear rate at time of peak brachial artery dilation was lower in patients with HFpEF compared with controls (HFpEF: 42 070±4018/s; CONTROLS: 69 018±9509/s, p=0.01), and when brachial artery FMD was normalised for the shear stimulus, cumulative area-under-the-curve (AUC) at peak dilation, the between-group differences were eliminated (HFpEF: 0.11±0.03%/AUC; CONTROLS: 0.09±0.01%/AUC, p=0.58). RH, assessed as AUC, was lower in patients with HFpEF (HFpEF: 454±35 mL; CONTROLS: 660±63 mL, p<0.01). CONCLUSIONS: Collectively, these data suggest that maladaptations at the microvascular level contribute to the pathophysiology of HFpEF, while conduit artery vascular function is not diminished beyond that which occurs with healthy aging.

Warm skin alters cardiovascular responses to cycling after preheating and precooling.

PURPOSE: Exercise in hot conditions increases core (TC) and skin temperature (TSK) and can lead to a progressive rise in HR and decline in stroke volume (SV) during prolonged exercise. Thermoregulatory-driven elevations in skin blood flow (SkBF) adds complexity to cardiovascular regulation during exercise in these conditions. Presently, the dominant, although debated, view is that raising TSK increases SkBF and reduces SV through diminished venous return; however, this scenario has not been rigorously investigated across core and skin temperatures. We tested the hypothesis that high TSK would raise HR and reduce SV during exercise after precooling (cold water bath) and preheating (hot water bath) and that no relationship would exist between SkBF and SV during exercise. METHODS: Non-endurance-trained individuals cycled for 20 min at 69% ± 1% VO2peak on four occasions: cool skin-cool core (SkCCC), warm skin-cool core (SkWCC), cool skin-warm core (SkCCW), and warm skin-warm core (SkWCW) on separate days. RESULTS: After precooling of TC, the rise in HR was greater in SkWCC than in SkCCC (P < 0.001), yet SV was similar (P = 0.26), which resulted in higher QC at min 20 in SkWCC (P < 0.01). Throughout exercise after preheating of TC, HR was higher (P < 0.001), SV was reduced (P < 0.01), and QC was similar (P = 0.40) in SkWCW versus SkCCW. When all trials were compared, there was no relationship between SkBF and SV (r = -0.08, P = 0.70); however, there was an inverse relationship between HR and SV (r = -0.75, P < 0.001). CONCLUSIONS: These data suggest that when TSK is elevated during exercise, HR and TC will rise but SV will only be reduced when TC is also elevated above 38°C. Furthermore, changes in SV are not related to changes in SkBF.

Hemodynamic responses to small muscle mass exercise in heart failure patients with reduced ejection fraction.

To better understand the mechanisms responsible for exercise intolerance in heart failure with reduced ejection fraction (HFrEF), the present study sought to evaluate the hemodynamic responses to small muscle mass exercise in this cohort. In 25 HFrEF patients (64 ± 2 yr) and 17 healthy, age-matched control subjects (64 ± 2 yr), mean arterial pressure (MAP), cardiac output (CO), and limb blood flow were examined during graded static-intermittent handgrip (HG) and dynamic single-leg knee-extensor (KE) exercise. During HG exercise, MAP increased similarly between groups. CO increased significantly (+1.3 ± 0.3 l/min) in the control group, but it remained unchanged across workloads in HFrEF patients. At 15% maximum voluntary contraction (MVC), forearm blood flow was similar between groups, while HFrEF patients exhibited an attenuated increase at the two highest intensities compared with controls, with the greatest difference at the highest workload (352 ± 22 vs. 492 ± 48 ml/min, HFrEF vs. control, 45% MVC). During KE exercise, MAP and CO increased similarly across work rates between groups. However, HFrEF patients exhibited a diminished leg hyperemic response across all work rates, with the most substantial decrement at the highest intensity (1,842 ± 64 vs. 2,675 ± 81 ml/min; HFrEF vs. control, 15 W). Together, these findings indicate a marked attenuation in exercising limb perfusion attributable to impairments in peripheral vasodilatory capacity during both arm and leg exercise in patients with HFrEF, which likely plays a role in limiting exercise capacity in this patient population.

Variability in orthostatic tolerance during heat stress: cerebrovascular reactivity to arterial carbon dioxide.

INTRODUCTION: A high degree of interindividual variability exists in the magnitude of heat stress (HS)-induced reductions in orthostatic tolerance relative to normothermia (NT). This variability may be associated with HS-mediated reductions in cerebral perfusion (indexed as middle cerebral artery blood velocity; MCAV(mean)) and altered cerebrovascular regulation. METHODS: We tested the hypothesis that cerebrovascular reactivity to hypocapnia would be positively correlated with differences in tolerance to lower body negative pressure (LBNP) [assessed with a cumulative stress index (CSI)] between HS and NT (CSI(diff)). Subjects (N = 13) underwent LBNP twice (NT and HS) separated by > 72 h to assess CSI. On a third day, cerebrovascular reactivity [changes in cerebral vascular conductance (CVCi) during hyperventilation-induced hypocapnia (indexed by end tidal carbon dioxide; P(ET)CO2)] was assessed during NT, HS, and HS+LBNP (-20 mmHg; HS(LBNP)). RESULTS: Tolerance to LBNP was reduced after a 1.5 +/- 0.1 degrees C increase in internal temperature and a high degree of variability was observed for CSI(diff) (range: 122 to 1826 mmHg x min(-1)). The magnitude of reduction in CVCi during voluntary hyperventilation-induced hypocapnia (-16 +/- 5 Torr) was attenuated during HS and HS(LBNP) VS. NT (NT: -0.20 +/- 0.09 cm x s(-1) x mmHg(-1); HS: -0.12 +/- 0.09 cm x s(-1) x mmHg(-1); HS(LBNP): -0.11 +/- 0.11 cm x s(-1). mmHg(-1)); however, no relationship existed between deltaCVCi/ P(ET)CO2 and CSI(diff) in any condition. CONCLUSIONS: Cerebrovascular reactivity to hyperventilation-induced hypocapnia is attenuated when internal temperature is elevated, perhaps as a protective mechanism to protect against further reductions in the already diminished cerebral perfusion in this thermal state. However, individual differences in these responses do not appear to predict orthostatic tolerance during HS.

Cerebral vasoreactivity: impact of heat stress and lower body negative pressure.

OBJECTIVE: Cerebrovascular reactivity represents the capacity of the cerebral circulation to raise blood flow in the face of increased demand, and may be reduced in some clinical and physiological conditions. We tested the hypothesis that the hypercapnia-induced increase in cerebral perfusion is attenuated during heat stress (HS) compared to normothermia (NT), and this response is further reduced during the combined challenges of HS and lower body negative pressure (LBNP). METHODS: Ten healthy individuals (9 men) undertook rebreathing-induced hypercapnia during NT, HS, and HS + 20 mmHg LBNP (HSLBNP), while cerebral perfusion was indexed from middle cerebral artery blood velocity (MCA V mean). Cerebrovascular responses were calculated from the slope of the change in MCA V mean and cerebral vascular conductance (CVCi) relative to the increase in end tidal carbon dioxide ([Formula: see text]) during rebreathing. RESULTS: MCA V mean was similar in HS (55 ± 19 cm s(-1)) and HSLBNP (52 ± 16 cm s(-1)), and both values were reduced relative to NT (66 ± 20 cm s(-1)), yet the rise in MCA V mean per Torr increase in [Formula: see text] during rebreathing was similar in each condition (NT: 2.5 ± 0.6 cm s(-1) Torr(-1); HS: 2.4 ± 0.8 cm s(-1) Torr(-1); HSLBNP: 2.1 ± 1.1 cm s(-1) Torr(-1)). Likewise, the rate of increase in CVCi was not different between conditions (NT: 2.1 ± 0.65 cm s(-1 )mmHg(-1)100 Torr(-1); HS: 2.4 ± 0.8 cm s(-1) mmHg(-1) 100 Torr(-1); HSLBNP: 2.0 ± 1.0 cm s(-1) mmHg(-1) 100 Torr(-1)). INTERPRETATIONS: These data indicate that cerebrovascular reactivity is not compromised during whole-body heat stress alone or when combined with mild orthostatic stress relative to normothermic conditions.

Elevated resting heart rate and reduced orthostatic tolerance in obese humans.

BACKGROUND: Obesity is linked with numerous physiological impairments; however, its impact on orthostatic tolerance (OT) remains unknown. This study tested the hypothesis that OT is reduced in obese individuals, and that reduced heart rate (HR) reserve and impaired cerebral autoregulation contribute to impaired OT. METHODS: Eleven obese (8 females) and 22 non-obese (10 females) individuals were exposed to incremental lower body negative pressure (LBNP) to presyncope while HR, arterial blood pressure, and cerebral perfusion (middle cerebral artery blood velocity; MCA V mean) were measured. OT was quantified with a cumulative stress index (CSI). RESULTS: OT was reduced in obese subjects, and there was an inverse relationship between body mass index (BMI) and OT (R = -0.47). HR was higher at rest and during each level of LBNP completed by all subjects. Similar peak HR (HRpeak) during LBNP between obese and non-obese subjects resulted in obese having a higher %peak HR at rest and at each stage of LBNP compared. Relationships existed for BMI and resting %HRpeak (R = 0.45) and resting %HRpeak and CSI (R = -0.52). Despite lower CSI in obese, MCA V mean and indices of cerebral autoregulation were similar between groups at all time points. CONCLUSIONS: These data suggest that OT is reduced in obese and a higher resting HR, but not impaired regulation of cerebral perfusion, may contribute to this reduction.

Effect of an aerodynamic helmet on head temperature, core temperature, and cycling power compared with a traditional helmet.

Nonvented "aerodynamic helmets" reduce wind resistance but may increase head (Th) and gastrointestinal (Tgi) temperature and reduce performance when worn in hot conditions. This study tested the hypothesis that Th and Tgi would be greater during low-intensity cycling (LIC) in the heat while wearing an aero helmet (AERO) vs. a traditional vented racing helmet (REG). This study also tested the hypothesis that Th, Tgi, and finish time would be greater, and power output would be reduced during a self-paced time trial in the heat with AERO vs. REG. Ten highly trained heat-acclimated endurance athletes conducted LIC (50% V[Combining Dot Above]O2max, LIC) and a high-intensity 12-km self-paced time trial (12-km TT) on a cycle ergometer in 39° C on 2 different days (AERO and REG), separated by >48 hours. During LIC, Th was higher at minute 7.5 and all time points thereafter in AERO vs. REG (p < 0.05). Similarly, during the 12-km TT, Th was higher at minutes 12.5, 15, and 17.5 in AERO vs. REG (p < 0.05). Heart rate (HR) and Tgi increased during LIC and during 12-km TT (both p < 0.001); however, no significant interaction (helmet × time) existed for HR or Tgi at either intensity (all p > 0.05). No group differences existed for finish time or power output during the 12-km TT (both p > 0.05). In conclusion, Th becomes elevated during cycling in the heat with an aero helmet compared with a traditional vented racing helmet during LIC and high-intensity cycling, yet Tgi and HR responses are similar irrespective of helmet type and Th. Furthermore, the higher Th that develops when an aero helmet is worn during cycling in the heat does not affect power output or cycling performance during short-duration high-intensity events.

The magnitude of heat stress-induced reductions in cerebral perfusion does not predict heat stress-induced reductions in tolerance to a simulated hemorrhage.

The mechanisms responsible for heat stress-induced reductions in tolerance to a simulated hemorrhage are unclear. Although a high degree of variability exists in the level of reduction in tolerance amongst individuals, syncope will always occur when cerebral perfusion is inadequate. This study tested the hypothesis that the magnitude of reduction in cerebral perfusion during heat stress is related to the reduction in tolerance to a lower body negative pressure (LBNP) challenge. On different days (one during normothermia and the other after a 1.5°C rise in internal temperature), 20 individuals were exposed to a LBNP challenge to presyncope. Tolerance was quantified as a cumulative stress index, and the difference in cumulative stress index between thermal conditions was used to categorize individuals most (large difference) and least (small difference) affected by the heat stress. Cerebral perfusion, as indexed by middle cerebral artery blood velocity, was reduced during heat stress compared with normothermia (P < 0.001); however, the magnitude of reduction did not differ between groups (P = 0.51). In the initial stage of LBNP during heat stress (LBNP 20 mmHg), middle cerebral artery blood velocity and end-tidal PCO(2) were lower; whereas, heart rate was higher in the large difference group compared with small difference group (P < 0.05 for all). These data indicate that variability in heat stress-induced reductions in tolerance to a simulated hemorrhage is not related to reductions in cerebral perfusion in this thermal condition. However, responses affecting cerebral perfusion during LBNP may explain the interindividual variability in tolerance to a simulated hemorrhage when heat stressed.

Interaction of hyperthermia and heart rate on stroke volume during prolonged exercise.

People who become hyperthermic during exercise display large increases in heart rate (HR) and reductions in stroke volume (SV). It is not clear if the reduction in SV is due primarily to hyperthermia or if it is a secondary effect of an elevation in HR reducing ventricular filling. In the present study, the upward drift of HR during prolonged exercise was prevented by a very small dose of the ß1-adrenoreceptor blocker (atenolol; ßB), thus allowing SV to be compared at a given HR during normothermia and hyperthermia. Eleven men cycled for 60 min at 57% of peak O2 uptake after receiving placebo control (PL) or a low dose (0.2 mg/kg) of ßB. Hyperthermia was induced by reducing heat dissipation during exercise. Four experimental conditions were studied: normothermia-PL, normothermia-ßB, hyperthermia-PL, and hyperthermia-ßB. Hyperthermia increased skin and core temperature by 4.3 degrees C and 0.8 degrees C (P<0.01), respectively. ßB prevented HR elevation with hyperthermia: HR values were similar at minute 60 during normothermia-PL and hyperthermia-ßB (155±11 and 154±13 beats/min, respectively, P=0.82). However, SV was increased by 7% during the final 20 min of exercise during hyperthermia-ßB compared with normothermia-PL (treatment×time interaction, P=0.03). In conclusion, when matched for HR, mild hyperthermia increased SV during exercise. Furthermore, the reduction in SV throughout prolonged exercise under normothermic and mildly hyperthermic conditions appears to be due to the increase in HR.