Fluid replacement and heat stress during exercise alter post-exercise cardiac haemodynamics in endurance exercise-trained men

It has been reported that endurance exercise-trained men have decreases in cardiac output with no change in systemic vascular conductance during post-exercise hypotension, which differs from sedentary and normally active populations. As inadequate hydration may explain these differences, we tested the hypothesis that fluid replacement prevents this post-exercise fall in cardiac output, and further, exercise in a warm environment would cause greater decreases in cardiac output. We studied 14 trained men (     4.66 ± 0.62 l min⁻¹) before and to 90 min after cycling at 60%     for 60 min under three conditions: Control (no water was consumed during exercise in a thermoneutral environment), Fluid (water was consumed to match sweat loss during exercise in a thermoneutral environment) and Warm (no water was consumed during exercise in a warm environment). Arterial pressure and cardiac output were measured pre- and post-exercise in a thermoneutral environment. The fall in mean arterial pressure following exercise was not different between conditions ( P = 0.453). Higher post-exercise cardiac output (Δ 0.41 ± 0.17 l min⁻¹; P = 0.027), systemic vascular conductance (Δ 6.0 ± 2.2 ml min⁻¹ mmHg⁻¹ ; P = 0.001) and stroke volume (Δ 9.1 ± 2.1 ml beat⁻¹; P < 0.001) were seen in Fluid compared to Control, but there was no difference between Fluid and Warm (all P > 0.05). These data suggest that fluid replacement mitigates the post-exercise decrease in cardiac output in endurance-exercise trained men. Surprisingly, exercise in a warm environment also mitigates the post-exercise fall in cardiac output.     

The rate of heat storage mediates an anticipatory reduction in exercise intensity during cycling at a fixed rating of perceived exertion

The aim of the present study was to examine the regulation of exercise intensity in hot environments when exercise is performed at a predetermined, fixed subjective rating of perceived exertion (RPE). Eight cyclists performed cycling trials at 15°C (COOL), 25°C (NORM) and 35°C (HOT) (65% humidity throughout), during which they were instructed to cycle at a Borg rating of perceived exertion (RPE) of 16, increasing or decreasing their power output in order to maintain this RPE. Power output declined linearly in all three trials and the rate of decline was significantly higher in HOT than in NORM and COOL (2.35 ± 0.73 W min⁻¹, 1.63 ± 0.70 and 1.61 ± 0.80 W min⁻¹, respectively, P < 0.05). The rate of heat storage was significantly higher in HOT for the first 4 min of the trials only, as a result of increasing skin temperatures. Thereafter, no differences in heat storage were found between conditions. We conclude that the regulation of exercise intensity is controlled by an initial afferent feedback regarding the rate of heat storage, which is used to regulate exercise intensity and hence the rate of heat storage for the remainder of the anticipated exercise bout. This regulation maintains thermal homeostasis by reducing the exercise work rate and utilizing the subjective RPE specifically to ensure that excessive heat accumulation does not occur and cellular catastrophe is avoided.     

Cerebral ammonia uptake and accumulation during prolonged exercise in humans

We evaluated whether peripheral ammonia production during prolonged exercise enhances the uptake and subsequent accumulation of ammonia within the brain. Two studies determined the cerebral uptake of ammonia (arterial and jugular venous blood sampling combined with Kety–Schmidt-determined cerebral blood flow; n = 5) and the ammonia concentration in the cerebrospinal fluid (CSF; n = 8) at rest and immediately following prolonged exercise either with or without glucose supplementation. There was a net balance of ammonia across the brain at rest and at 30 min of exercise, whereas 3 h of exercise elicited an uptake of 3.7 ± 1.3 μmol min⁻¹ (mean ± s.e.m. ) in the placebo trial and 2.5 ± 1.0 μmol min⁻¹ in the glucose trial ( P < 0.05 compared to rest, not different across trials). At rest, CSF ammonia was below the detection limit of 2 μ m in all subjects, but it increased to 5.3 ± 1.1 μ m following exercise with glucose, and further to 16.1 ± 3.3 μ m after the placebo trial ( P < 0.05). Correlations were established between both the cerebral uptake  ( r ²= 0.87; P < 0.05)  and the CSF concentration  ( r ²= 0.72; P < 0.05)  and the arterial ammonia level and, in addition, a weaker correlation  ( r ²= 0.37; P < 0.05)  was established between perceived exertion and CSF ammonia at the end of exercise. The results let us suggest that during prolonged exercise the cerebral uptake and accumulation of ammonia may provoke fatigue, e.g. by affecting neurotransmitter metabolism.     

Interleukin-6 release from the human brain during prolonged exercise

Interleukin (IL)-6 is a pleiotropic cytokine, which has a variety of physiological roles including functions within the central nervous system. Circulating IL-6 increases markedly during exercise, partly due to the release of IL-6 from the contracting skeletal muscles, and exercise-induced IL-6 may be linked with central fatigue, which is enhanced by hyperthermia. Exercise-induced IL-6 may also stimulate hepatic glycogenolysis, which is important during prolonged and repeated exercise. Thus, in a randomised order and separated by 60 min of rest, eight young male subjects completed two 60 min exercise bouts: one bout with a normal (38 °C) and the other with an elevated (39.5 °C) core temperature. The cerebral IL-6 response was determined on the basis of internal jugular venous to arterial IL-6 differences and global cerebral blood flow. There was no net release or uptake of IL-6 in the brain at rest or after 15 min of exercise, but a small release of IL-6 was observed after 60 min of exercise in the first bout (0.06 ± 0.03 ng min⁻¹). This release of IL-6 from the brain was five-fold greater at the end of the second bout (0.30 ± 0.08 ng min⁻¹; P < 0.05) with no separate influence of hyperthermia. In conclusion, IL-6 is released from the brain during prolonged exercise in humans and it appears that the duration of the exercise rather than the increase in body temperature dictates the cerebral IL-6 response.     

Inadequate heat release from the human brain during prolonged exercise with hyperthermia

Brain temperature appears to be an important factor affecting motor activity, but it is not known to what extent brain temperature increases during prolonged exercise in humans. Cerebral heat exchange was therefore evaluated in seven males during exercise with and without hyperthermia. Middle cerebral artery mean blood velocity (MCA V _mean) was continuously monitored while global cerebral blood flow (CBF) and cerebral energy turnover were determined at the end of the two exercise trials in three subjects. The arterial to venous temperature difference across the brain (v-a D _temp) was determined via thermocouples placed in the internal jugular vein and in the aorta. The jugular venous blood temperature was always higher than that of the arterial blood, demonstrating that heat was released via the CBF during the normothermic as well as the hyperthermic exercise condition. However, heat removal via the jugular venous blood was 30 ± 6 % lower during hyperthermia compared to the control trial. The reduced heat removal from the brain was mainly a result of a 20 ± 6 % lower CBF (22 ± 9 % reduction in MCA V _mean), because the v-a D _temp was not significantly different in the hyperthermic (0.20 ± 0.05 °C) compared to the control trial (0.22 ± 0.05 °C). During hyperthermia, the impaired heat removal via the blood was combined with a 7 ± 2 % higher heat production in the brain and heat was consequently stored in the brain at a rate of 0.20 ± 0.06 J g⁻¹ min⁻¹. The present results indicate that the average brain temperature is at least 0.2 °C higher than that of the body core during exercise with or without hyperthermia.     

A respiratory response to the activation of the muscle metaboreflex during concurrent hypercapnia in man

In this study, we aimed to assess the ventilatory and cardiovascular responses to the combined activation of the muscle metaboreflex and the ventilatory chemoreflex, achieved by postexercise circulatory occlusion (PECO) and euoxic hypercapnia (end-tidal partial pressure of CO₂ 7 mmHg above normal), respectively. Eleven healthy subjects (4 women and 7 men; 29 ± 4.4 years old; mean ± s.d. ) undertook the following four trials, in random order: 2 min of isometric handgrip exercise followed by 2 min of PECO with hypercapnia; 2 min of isometric handgrip exercise followed by 2 min of PECO while breathing room air; 4 min of rest with hypercapnia; and 4 min of rest while breathing room air. Ventilation was significantly increased during exercise in both the hypercapnic (+3.17 ± 0.82 l min⁻¹) and the room air breathing trials (+2.90 ± 0.26 l min⁻¹; all P < 0.05). During PECO, ventilation returned to pre-exercise levels when breathing room air (+0.52 ± 0.37 l min⁻¹; P > 0.05), but it remained elevated during hypercapnia (+3.77 ± 0.23 l min⁻¹; P < 0.05). The results indicate that the muscle metaboreflex stimulates ventilation with concurrent chemoreflex activation. These findings have implications for disease states where effort intolerance and breathlessness are linked.     

Arm Blood Flow and Oxygenation on the Transition from Arm to Combined Arm and Leg Exercise in Humans

The cardiovascular response to exercise with several groups of skeletal muscle implies that work with the legs may reduce arm blood flow. This study followed arm blood flow ( _arm) and oxygenation on the transition from arm cranking (A) to combined arm and leg exercise (A+L). Seven healthy male subjects performed A at ∼80 % of maximum work rate ( W _max) and A at ∼80 % W _max combined with L at ∼60 % W _max. A transition trial to volitional exhaustion was performed where L was added after 2 min of A. The _arm was determined by constant infusion thermodilution in the axillary vein and changes in biceps muscle oxygenation were measured with near-infrared spectroscopy. During A+L _arm was lowered by 0.38 ± 0.06 l min⁻¹ (10.4 ± 3.3 %,   P < 0.05  ) from 2.96 ± 1.54 l min⁻¹ during A. Total (HbT) and oxygenated haemoglobin (HbO₂) concentrations were also lower. During the transition from A to A+L _arm decreased by 0.22 ± 0.03 l min⁻¹ (7.9 ± 1.8 %,   P < 0.05  ) within 9.6 ± 0.2 s, while HbT and HbO₂ decreased similarly within 30 ± 2 s. At the same time mean arterial pressure and arm vascular conductance also decreased. The data demonstrate reduction in blood flow to active skeletal muscle during maximal whole body exercise to a degree that arm oxygen uptake and muscle tissue oxygenation are compromised.     

Effect of dexamethasone on skeletal muscle Na+,K+ pump subunit specific expression and K+ homeostasis during exercise in humans

The effect of dexamethasone on Na⁺,K⁺ pump subunit expression and muscle exchange of K⁺ during exercise in humans was investigated. Nine healthy male subjects completed a randomized double blind placebo controlled protocol, with ingestion of dexamethasone (Dex: 2 × 2 mg per day) or placebo (Pla) for 5 days. Na⁺,K⁺ pump catalytic α1 and α2 subunit expression was ∼17% higher ( P < 0.05) and the structural β1 and β2 subunit expression was ∼6–8% higher ( P < 0.05) after Dex compared with Pla. During one-legged knee-extension for 10 min at low intensity (LI; 18.6 ± 1.0 W), two moderate intensity (51.7 ± 2.4 W) exercise bouts (MI₁: 5 min; 2 min recovery; MI₂: exhaustive) and two high-intensity (71.7 ± 2.5 W) exercise bouts (HI₁: 1 min 40 s; 2 min recovery; HI₂: exhaustive), femoral venous K⁺ was lower ( P < 0.05) in Dex compared with Pla. Thigh K⁺ release was lower ( P < 0.05) in Dex compared with Pla in LI and MI, but not in HI. Time to exhaustion in MI₂ tended to improve (393 ± 50 s versus 294 ± 41 s; P = 0.07) in Dex compared with Pla, whereas no difference was detected in HI₂ (106 ± 10 s versus 108 ± 9 s). The results indicate that an increased Na⁺,K⁺ pump expression per se is of importance for thigh K⁺ reuptake at the onset of low and moderate intensity exercise, but less important during high intensity exercise.     

Local metabolite accumulation augments passive muscle stretch-induced modulation of carotid–cardiac but not carotid–vasomotor baroreflex sensitivity in man

We examined the effects of muscle mechanoreflex stimulation by passive calf muscle stretch, at rest and during concurrent muscle metaboreflex activation, on carotid baroreflex (CBR) sensitivity. Twelve subjects either performed 1.5 min one-legged isometric plantarflexion at 50% maximal voluntary contraction with their right or left calf [two ischaemic exercise (IE) trials, IER and IEL] or rested for 1.5 min [two ischaemic control (IC) trials, ICR and ICL]. Following exercise, blood pressure elevation was partly maintained by local circulatory occlusion (CO). 3.5 min of CO was followed by 3 min of CO with passive stretch (STR-CO) of the right calf in all trials. Carotid baroreflex function was assessed using rapid pulses of neck pressure from +40 to −80 mmHg. In all IC trials, stretch did not alter maximal gain of carotid–cardiac (CBR–HR) and carotid–vasomotor (CBR–MAP) baroreflex function curves. The CBR–HR curve was reset without change in maximal gain during STR-CO in the IEL trial. However, during the IER trial maximal gain of the CBR–HR curve was smaller than in all other trials (−0.34 ± 0.04 beats min⁻¹ mmHg⁻¹ in IER versus −0.76 ± 0.20, −0.94 ± 0.14 and −0.66 ± 0.18 beats min⁻¹ mmHg⁻¹ in ICR, IEL and ICL, respectively), and significantly smaller than in IEL ( P < 0.05). The CBR–MAP curves were reset from CO values by STR-CO in the IEL and IER trials with no changes in maximal gain. These results suggest that metabolite sensitization of stretch-sensitive muscle mechanoreceptive afferents modulates baroreflex control of heart rate but not blood pressure.     

Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow was quantified by near infrared spectroscopy and indocyanine green in six healthy humans during dynamic knee extension exercise with and without combined pharmacological inhibition of NO synthase (NOS) and PG by l -NAME and indomethacin, respectively. Microdialysis was applied to determine interstitial release of PG. Compared to control, combined blockade resulted in a 5- to 10-fold lower muscle interstitial PG level. During control incremental knee extension exercise, mean blood flow in the quadriceps muscles rose from 10 ± 0.8 ml (100 ml tissue)⁻¹ min⁻¹ at rest to 124 ± 19, 245 ± 24, 329 ± 24 and 312 ± 25 ml (100 ml tissue)⁻¹ min⁻¹ at 15, 30, 45 and 60 W, respectively. During inhibition of NOS and PG, blood flow was reduced to 8 ± 0.5 ml (100 ml tissue)⁻¹ min⁻¹ at rest, and 100 ± 13, 163 ± 21, 217 ± 23 and 256 ± 28 ml (100 ml tissue)⁻¹ min⁻¹ at 15, 30, 45 and 60 W, respectively ( P < 0.05 vs. control). In conclusion, combined inhibition of NOS and PG reduced muscle blood flow during dynamic exercise in humans. These findings demonstrate an important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular contraction.     

No effect of growth hormone administration on substrate oxidation during exercise in young, lean men

The purpose of this study was to examine the effects of increased fat availability induced by growth hormone (GH) administration on the oxidative metabolism during exercise. Seven well-trained males (age 25 ± 2 years (mean ± s.e.m. ); peak oxygen consumption     : 62 ± 1 ml min⁻¹ kg⁻¹ (completed four randomised trials: 120 min bicycling at 55%     4 h after receiving either 7.5 IU (2.5 mg) GH or placebo (Plc), and during rest after receiving either GH or Plc. In all studies a standardized meal was given 2 h after GH or Plc injection. GH administration resulted in an ∼60-fold increase in serum GH concentration at rest ( P < 0.0001) and during exercise ( P < 0.0001). The increase in serum GH was followed by an increase in circulating glycerol at rest (8%, P < 0.0001). When combined with exercise the increase in plasma glycerol was more pronounced (GH: 716% of baseline versus Plc: 328%, P < 0.0001). However, this increase in fat mobilization did not increase fat oxidation during exercise (indirect calorimetry). In conclusion, GH administration combined with aerobic exercise increased lipolytic parameters substantially more than exercise alone, but did not further augment whole body fat oxidation.     

Influence of brain catecholamines on the development of fatigue in exercising rats in the heat

The purpose of the present study was to identify the effects of an acute injection of a dual dopamine (DA)/noradrenaline (NA) reuptake inhibitor (bupropion) on exercise performance, thermoregulation and neurotransmitters in the preoptic area and anterior hypothalamus (PO/AH) of the rat during exercise in the heat. Body core temperature (T(core)), brain temperature (T(brain)) and tail skin temperature (T(tail)) were measured. A microdialysis probe was inserted in the PO/AH, and samples for measurement of extracellular DA, NA and serotonin (5-HT) levels were collected. Rats received either bupropion (17 mg kg(-1); hot-BUP) or saline (1 ml kg(-1); hot) 20 min before the start of exercise and ran at a speed of 26 m min(-1) until exhaustion in a warm environment (30 degrees C). Rats also ran until exhaustion in a cool environment (18 degrees C; cool). Running time to exhaustion was significantly influenced by the ambient temperature, and it was increased by bupropion in the heat (cool, 143.6 +/- 21 min; hot, 65.8 +/- 13 min; hot-BUP, 86.3 +/- 7.2 min). T(core) and T(brain) at exhaustion were significantly higher in the bupropion group compared to the cool and hot groups, respectively. T(tail) measured at exhaustion was not significantly different between the two hot conditions. Extracellular concentrations of DA and NA in the PO/AH increased during exercise, and was significantly higher in the bupropion than in cool and hot groups (P < 0.05). No differences were observed between groups for 5-HT levels. These results suggest that DA and NA in the PO/AH might be responsible for the increase in exercise performance and T(core) and T(brain) in the bupropion group in hyperthermia. Moreover, these results support previous findings in humans that acute bupropion ingestion increases T(core) during exercise in the heat, indicating the possibility of an important role for DA and NA in thermoregulation.     

Effects of a prior high-intensity knee-extension exercise on muscle recruitment and energy cost: a combined local and global investigation in humans

The effects of a priming exercise bout on both muscle energy production and the pattern of muscle fibre recruitment during a subsequent exercise bout are poorly understood. The purpose of the present study was to determine whether a prior exercise bout which is known to increase O₂ supply and to induce a residual acidosis could alter energy cost and muscle fibre recruitment during a subsequent heavy-intensity knee-extension exercise. Fifteen healthy subjects performed two 6 min bouts of heavy exercise separated by a 6 min resting period. Rates of oxidative and anaerobic ATP production, determined with ³¹P-magnetic resonance spectroscopy, and breath-by-breath measurements of pulmonary oxygen uptake were obtained simultaneously. Changes in muscle oxygenation and muscle fibre recruitment occurring within the quadriceps were measured using near-infrared spectroscopy and surface electromyography. The priming heavy-intensity exercise increased motor unit recruitment ( P < 0.05) in the early part of the subsequent exercise bout but did not alter muscle energy cost. We also observed a reduced deoxygenation time delay, whereas the deoxygenation amplitude was increased ( P < 0.01). These changes were associated with an increased oxidative ATP cost after ∼50 s ( P < 0.05) and a slight reduction in the overall anaerobic rate of ATP production (0.11 ± 0.04 m m min⁻¹ W⁻¹ for bout 1 and 0.06 ± 0.11 m m min⁻¹ W⁻¹ for bout 2; P < 0.05). We showed that a priming bout of heavy exercise led to an increased recruitment of motor units in the early part of the second bout of heavy exercise. Considering the increased oxidative cost and the unaltered energy cost, one could suggest that our results illustrate a reduced metabolic strain per fibre.     

Cytochrome P450 2C9 plays an important role in the regulation of exercise-induced skeletal muscle blood flow and oxygen uptake in humans

Previous studies show that exercise-induced hyperaemia is unaffected by systemic inhibition of nitric oxide synthase (NOS) and it has been proposed that this may be due to compensation by other vasodilators. We studied the involvement of cytochrome P450 2C9 (CYP 2C9) in the regulation of skeletal muscle blood flow in humans and the interaction between CYP 2C9 and NOS. Seven males performed knee extensor exercise. Blood flow was measured by thermodilution and blood samples were drawn frequently from the femoral artery and vein at rest, during exercise and in recovery. The protocol was repeated three times on the same day. The first and the third protocols were controls, and in the second protocol either the CYP 2C9 inhibitor sulfaphenazole alone, or sulfaphenazole in combination with the NOS inhibitor N ^ω-monomethyl- l -arginine ( l -NMMA) were infused. Compared with control there was no difference in blood flow at any time with sulfaphenazole infusion (   P > 0.05  ) whereas with infusion of sulfaphenazole and l -NMMA, blood flow during exercise was 16 ± 4 % lower than in control (9 min: 3.67 ± 0.31 vs. 4.29 ± 0.20 l min⁻¹;   P < 0.05  ). Oxygen uptake during exercise was 12 ± 3 % lower (9 min: 525 ± 46 vs. 594 ± 24 ml min⁻¹;   P < 0.05  ) with co-infusion of sulfaphenazole and l -NMMA, whereas oxygen uptake during sulfaphenazole infusion alone was not different from that of control (   P > 0.05  ). The results demonstrate that CYP 2C9 plays an important role in the regulation of hyperaemia and oxygen uptake during exercise. Since inhibition of neither NOS nor CYP 2C9 alone affect skeletal muscle blood flow, an interaction between CYP 2C9 and NOS appears to exist so that a CYP-dependent vasodilator mechanism takes over when NO production is compromised.     

Nitric oxide contributes to the augmented vasodilatation during hypoxic exercise

We tested the hypotheses that (1) nitric oxide (NO) contributes to augmented skeletal muscle vasodilatation during hypoxic exercise and (2) the combined inhibition of NO production and adenosine receptor activation would attenuate the augmented vasodilatation during hypoxic exercise more than NO inhibition alone. In separate protocols subjects performed forearm exercise (10% and 20% of maximum) during normoxia and normocapnic hypoxia (80% arterial O₂ saturation). In protocol 1 ( n = 12), subjects received intra-arterial administration of saline (control) and the NO synthase inhibitor N ^G-monomethyl- l -arginine ( l -NMMA). In protocol 2 ( n = 10), subjects received intra-arterial saline (control) and combined l -NMMA–aminophylline (adenosine receptor antagonist) administration. Forearm vascular conductance (FVC; ml min⁻¹ (100 mmHg)⁻¹) was calculated from forearm blood flow (ml min⁻¹) and blood pressure (mmHg). In protocol 1, the change in FVC (Δ from normoxic baseline) due to hypoxia under resting conditions and during hypoxic exercise was substantially lower with l -NMMA administration compared to saline (control; P < 0.01). In protocol 2, administration of combined l -NMMA–aminophylline reduced the ΔFVC due to hypoxic exercise compared to saline (control; P < 0.01). However, the relative reduction in ΔFVC compared to the respective control (saline) conditions was similar between l -NMMA only (protocol 1) and combined l -NMMA–aminophylline (protocol 2) at 10% (−17.5 ± 3.7 vs. −21.4 ± 5.2%; P = 0.28) and 20% (−13.4 ± 3.5 vs. −18.8 ± 4.5%; P = 0.18) hypoxic exercise. These findings suggest that NO contributes to the augmented vasodilatation observed during hypoxic exercise independent of adenosine.     

Cardiac and vasomotor components of the carotid baroreflex control of arterial blood pressure during isometric exercise in humans

We sought to examine the importance of the cardiac component of the carotid baroreflex (CBR) in control of blood pressure during isometric exercise. Nine subjects performed 4 min of ischaemic isometric calf exercise at 20% of maximum voluntary contraction. Trials were repeated with β₁-adrenergic blockade (metoprolol, 0.15 ± 0.003 mg kg⁻¹) or parasympathetic blockade (glycopyrrolate, 13.6 ± 1.5 μg kg⁻¹). CBR function was determined using rapid pulses of neck pressure and neck suction from +40 to −80 mmHg, while heart rate (HR), mean arterial pressure (MAP) and changes in stroke volume (SV, Modelflow method) were measured. Metoprolol decreased and glycopyrrolate increased HR and cardiac output both at rest and during exercise ( P < 0.05), while resting and exercising blood pressure were unchanged. Glycopyrrolate reduced the maximal gain ( G _max) of the CBR-HR function curve (−0.58 ± 0.10 to −0.06 ± 0.01 beats min⁻¹ mmHg⁻¹, P < 0.05), but had no effect on the G _max of the CBR-MAP function curve. During isometric exercise the CBR-HR curve was shifted upward and rightward in the metoprolol and no drug conditions, while the control of HR was significantly attenuated with glycopyrrolate ( P < 0.05). Regardless of drug administration isometric exercise produced an upward and rightward resetting of the CBR control of MAP with no change in G _max. Thus, despite marked reductions in CBR control of HR following parasympathetic blockade, CBR control of blood pressure was well maintained. These data suggest that alterations in vasomotor tone are the primary mechanism by which the CBR modulates blood pressure during low intensity isometric exercise.     

Sustained and generalized extracellular fluid expansion following heat acclimation

We measured intra- and extravascular body-fluid compartments in 12 resting males before (day 1; control), during (day 8) and after (day 22) a 3-week, exercise–heat acclimation protocol to investigate plasma volume (PV) changes. Our specific focus was upon the selective nature of the acclimation-induced PV expansion, and the possibility that this expansion could be sustained during prolonged acclimation. Acclimation was induced by cycling in the heat, and involved 16 treatment days (controlled hyperthermia (90 min); core temperature = 38.5°C) and three experimental exposures (40 min rest, 96.9 min ( s.d. 9.5 min) cycling), each preceded by a rest day. The environmental conditions were a temperature of 39.8°C ( s.d. 0.5°C) and relative humidity of 59.2% ( s.d. 0.8%). On days 8 and 22, PV was expanded and maintained relative to control values (day 1: 44.0 ± 1.8; day 8: 48.8 ± 1.7; day 22: 48.8 ± 2.0 ml kg⁻¹; P < 0.05). The extracellular fluid compartment (ECF) was equivalently expanded from control values on days 8 (279.6 ± 14.2 versus 318.6 ± 14.3 ml kg⁻¹; n = 8; P < 0.05) and 22 (287.5 ± 10.6 versus 308.4 ± 14.8 ml kg⁻¹; n = 12; P < 0.05). Plasma electrolyte, total protein and albumin concentrations were unaltered following heat acclimation ( P > 0.05), although the total plasma content of these constituents was elevated ( P < 0.05). The PV and interstitial fluid (ISF) compartments exhibited similar relative expansions on days 8 (15.0 ± 2.2% versus 14.7 ± 4.1%; P > 0.05) and 22 (14.4 ± 3.6% versus 6.4 ± 2.2%; P = 0.10). It is concluded that the acclimation-induced PV expansion can be maintained following prolonged heat acclimation. In addition, this PV expansion was not selective, but represented a ubiquitous expansion of the extracellular compartment.     

Neurovascular responses to mental stress

The effects of mental stress (MS) on muscle sympathetic nerve activity (MSNA) and limb blood flows have been studied independently in the arm and leg, but they have not been studied collectively. Furthermore, the cardiovascular implications of postmental stress responses have not been thoroughly addressed. The purpose of the current investigation was to comprehensively examine concurrent neural and vascular responses during and after mental stress in both limbs. In Study 1, MSNA, blood flow (plethysmography), mean arterial pressure (MAP) and heart rate (HR) were measured in both the arm and leg in 12 healthy subjects during and after MS (5 min of mental arithmetic). MS significantly increased MAP (Δ15 ± 3 mmHg; P < 0.01) and HR (Δ19 ± 3 beats min⁻¹; P < 0.01), but did not change MSNA in the arm (14 ± 3 to 16 ± 3 bursts min⁻¹; n = 6) or leg (14 ± 2 to 15 ± 2 bursts min⁻¹; n = 8). MS decreased forearm vascular resistance (FVR) by −27 ± 7% ( P < 0.01; n = 8), while calf vascular resistance (CVR) did not change (−6 ± 5%; n = 11). FVR returned to baseline during recovery, whereas MSNA significantly increased in the arm (21 ± 3 bursts min⁻¹; P < 0.01) and leg (19 ± 3 bursts min⁻¹; P < 0.03). In Study 2, forearm and calf blood flows were measured in an additional 10 subjects using Doppler ultrasound. MS decreased FVR (−27 ± 10%; P < 0.02), but did not change CVR (5 ± 14%) as in Study 1. These findings demonstrate differential vascular control of the arm and leg during MS that is not associated with muscle sympathetic outflow. Additionally, the robust increase in MSNA during recovery may have acute and chronic cardiovascular implications.     

Baroreflex-Mediated Changes in Cardiac Output and Vascular Conductance in Response to Alterations in Carotid Sinus Pressure during Exercise in Humans

We sought to quantify the contribution of cardiac output ( Q ) and total vascular conductance (TVC) to carotid baroreflex (CBR)-mediated changes in mean arterial pressure (MAP) during mild to heavy exercise. CBR function was determined in eight subjects (25 ± 1 years) at rest and during three cycle exercise trials at heart rates (HRs) of 90, 120 and 150 beats min⁻¹ performed in random order. Acute changes in carotid sinus transmural pressure were evoked using 5 s pulses of neck pressure (NP) and neck suction (NS) from +40 to −80 Torr (+5.33 to −10.67 kPa). Beat-to-beat changes in HR and MAP were recorded throughout. In addition, stroke volume (SV) was estimated using the Modelflow method, which incorporates a non-linear, three-element model of the aortic input impedance to compute an aortic flow waveform from the arterial pressure wave. The application of NP and NS did not cause any significant changes in SV either at rest or during exercise. Thus, CBR-mediated alterations in Q were solely due to reflex changes in HR. In fact, a decrease in the carotid-HR response range from 26 ± 7 beats min⁻¹ at rest to 7 ± 1 beats min⁻¹ during heavy exercise (   P = 0.001  ) reduced the contribution of Q to the CBR-mediated change in MAP. More importantly, at the time of the peak MAP response, the contribution of TVC to the CBR-mediated change in MAP was increased from 74 ± 14 % at rest to 118 ± 6 % (   P = 0.017  ) during heavy exercise. Collectively, these findings indicate that alterations in vasomotion are the primary means by which the CBR regulates blood pressure during mild to heavy exercise.     

Central command and the cutaneous vascular response to isometric exercise in heated humans

Cutaneous vascular conductance (CVC) decreases during isometric handgrip exercise in heat stressed individuals, and we hypothesized that central command is involved in this response. Seven subjects performed 2 min of isometric handgrip exercise (35% of maximal voluntary contraction) followed by postexercise ischaemia in normothermia and during heat stress (increase in internal temperature ∼1°C). To augment the contribution of central command independent of force generation, on a separate day the protocol was repeated following partial neuromuscular blockade (PNB; i.v. cisatracurium). Forearm skin blood flow was measured by laser-Doppler flowmetry, and CVC was the ratio of skin blood flow to mean arterial pressure. The PNB attenuated force production despite encouragement to attain the same workload. During the heat stress trials, isometric exercise decreased CVC by ∼12% for both conditions, but did not change CVC in either of the normothermic trials. During isometric exercise in the heat, the increase in mean arterial pressure (MAP) was greater during the control trial relative to the PNB trial (31.0 ± 9.8 versus 18.6 ± 6.4 mmHg, P < 0.01), while the elevation of heart rate tended to be lower (19.4 ± 10.4 versus 27.4 ± 8.1 b.p.m., P = 0.15). During postexercise ischaemia, CVC and MAP returned to pre-exercise levels in the PNB trial but remained reduced in the control trial. These findings suggest that central command, as well as muscle metabo-sensitive afferent stimulation, contributes to forearm cutaneous vascular responses in heat stressed humans.