Bodil Nielsen

Human circulatory and thermoregulatory adaptations with heat acclimation and exercise in a hot, dry environment.

1. Heat acclimation was induced in eight subjects by asking them to exercise until exhaustion at 60% of maximum oxygen consumption rate (VO2) for 9‐12 consecutive days at an ambient temperature of 40 degrees C, with 10% relative humidity (RH). Five control subjects exercised similarly in a cool environment, 20 degrees C, for 90 min for 9‐12 days; of these, three were exposed to exercise at 40 degrees C on the first and last day. 2. Acclimation had occurred as seen by the increased average endurance from 48 min to 80 min, the lower rate of rise in the heart rate (HR) and core temperature and the increased sweating. 3. Cardiac output increased significantly from the first to the final heat exposure from 19.6 to 21.4 l min‐1; this was possibly due to an increased plasma volume and stroke volume. 4. The mechanism for the increased plasma volume may be an isosmotic volume expansion caused by influx of protein to the vascular compartment, and a sodium retention induced by a significant increase in aldosterone. 5. The exhaustion coincided with, or was elicited when, core temperature reached 39.7 +/‐ 0.15 degrees C; with progressing acclimation processes it took progressively longer to reach this level. However, at this point we found no reduction in cardiac output, muscle (leg) blood flow, no changes in substrate utilization or availability, and no recognized accumulated ‘fatigue’ substances. 6. It is concluded that the high core temperature per se, and not circulatory failure, is the critical factor for the exhaustion during exercise in heat stress.

Muscle blood flow is reduced with dehydration during prolonged exercise in humans

1 The present study examined whether the blood flow to exercising muscles becomes reduced when cardiac output and systemic vascular conductance decline with dehydration during prolonged exercise in the heat. A secondary aim was to determine whether the upward drift in oxygen consumption (V̇O2) during prolonged exercise is confined to the active muscles. 2 Seven euhydrated, endurance‐trained cyclists performed two bicycle exercise trials in the heat (35 °C; 40–50% relative humidity; 61 ± 2% of maximal V̇O2), separated by 1 week. During the first trial (dehydration trial, DE), they bicycled until volitional exhaustion (135 ± 4 min, mean ± s.e.m.), while developing progressive dehydration and hyperthermia (3.9 ± 0.3% body weight loss; 39.7 ± 0.2 °C oesophageal temperature, Toes). In the second trial (control trial), they bicycled for the same period of time while maintaining euhydration by ingesting fluids and stabilizing Toes at 38.2 ± 0.1 °C after 30 min exercise. 3 In both trials, cardiac output, leg blood flow (LBF), vascular conductance and V̇O2 were similar after 20 min exercise. During the 20 min‐exhaustion period of DE, cardiac output, LBF and systemic vascular conductance declined significantly (8–14%; P < 0.05) yet muscle vascular conductance was unaltered. In contrast, during the same period of control, all these cardiovascular variables tended to increase. After 135 ± 4 min of DE, the 2.0 ± 0.6 l min−1 lower blood flow to the exercising legs accounted for approximately two‐thirds of the reduction in cardiac output. Blood flow to the skin also declined markedly as forearm blood flow was 39 ± 8% (P < 0.05) lower in DE vs. control after 135 ± 4 min. 4 In both trials, whole body V̇O2 and leg V̇O2 increased in parallel and were similar throughout exercise. The reduced leg blood flow in DE was accompanied by an even greater increase in femoral arterial‐venous O2 (a‐vO2) difference. 5 It is concluded that blood flow to the exercising muscles declines significantly with dehydration, due to a lowering in perfusion pressure and systemic blood flow rather than increased vasoconstriction. Furthermore, the progressive increase in oxygen consumption during exercise is confined to the exercising skeletal muscles.

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 Vmean) 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‐aDtemp) 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 Vmean), because the v‐aDtemp 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.

Middle cerebral artery blood velocity is reduced with hyperthermia during prolonged exercise in humans.

1 In the present study we examined the effect of hyperthermia on the middle cerebral artery mean blood velocity (MCA Vmean) during prolonged exercise. We predicted that the cerebral circulation would be impaired when hyperthermia is present during exercise and assumed that this could be observed as a reduced MCA Vmean. 2 Eight endurance trained men (maximum oxygen uptake (V̇O2,max) 70 ± 1 ml min−1 kg−1 (mean ±s.e.m.)) performed two exercise trials at 57 % of V̇O2,max on a cycle ergometer in a hot (40 °C; hyperthermic trial) and in a thermoneutral environment (18 °C; control trial). In the hyperthermic trial, the oesophageal temperature increased throughout the exercise period reaching a peak value of 40.0 ± 0.1 °C at exhaustion after 53 ± 4 min of exercise. In the control trial, exercise was maintained for 1 h without any signs of fatigue and with core temperature stabilised at 37.8 ± 0.1 °C after ≈15 min of exercise. 3 Concomitant with the development of hyperthermia, MCA Vmean declined by 26 ± 3 % from 73 ± 4 cm s−1 at the beginning of exercise to 54 ± 4 cm s−1 at exhaustion (P < 0.001). In contrast, MCA Vmean remained unchanged at 70‐72 cm s−1 throughout the 1 h control trial. 4 When individually determined regression lines for MCA Vmean and arterial carbon dioxide pressure (Pa,CO2) obtained during preliminary exercise tests were used to account for the differences in Pa,CO2 between the hyperthermic and control trial, it appeared that more than half of the reduction in MCA Vmean (56 ± 8 %) was related to a hyperventilation‐induced drop in Pa,CO2. Declining cardiac output and arterial blood pressure accounted for the remaining part of the hyperthermia‐induced reduction in MCA Vmean. 5 The present results demonstrate that the development of hyperthermia during prolonged exercise is associated with a marked reduction in MCA Vmean.

Cerebral changes during exercise in the heat.

AbstractThis review focuses on cerebral changes during combined exercise and heat stress, and their relation to fatigue. Dynamic exercise can elevate the core temperature rapidly and high internal body temperatures seem to be an independent cause of fatigue during exercise in hot environments. Thus, in laboratory settings, trained participants become exhausted when they reach a core temperature of ∼40°C. The observation that exercise-induced hyperthermia reduces the central activation percentage during maximal isometricmuscle contractions supports the idea that central fatigue is involved in the aetiology of hyperthermia-induced fatigue. Thus, hyperthermia does not impair the ability of the muscles to generate force, but sustained force production is lowered as a consequence of a reduced neural drive from the CNS. During ongoing dynamic exercise in hot environments, there is a gradual slowing of the electroencephalogram (EEG) whereas hyperthermia does not affect the electromyogram. The frequency shift of the EEG is highly correlated with the participants’ perception of exertion, which furthermore may indicate that alterations in cerebral activity, rather than peripheral fatigue, are associated with the hyperthermia-induced development of fatigue. Cerebral blood flow is reduced by approximately 20% during exercise with hyperthermia due to hyperventilation,which causes a lowering of the arterial CO2 pressure. However, in spite of the reduced blood flow, cerebral glucose and oxygen uptake does not seem to be impaired. Removal of heat from the brain is also an important function of the cerebral blood flow and the lowered perfusion of the brain during exercise and heat stress appears to reduce heat removal by the venous blood. Heat is consequently stored in the brain. The causal relationship between the circulatory changes, the EEG changes and the hyperthermia-induced central fatigue is at the present not well understood and future studies should focus on this aspect.

Metabolic and thermodynamic responses to dehydration‐induced reductions in muscle blood flow in exercising humans

1 The present study examined whether reductions in muscle blood flow with exercise‐induced dehydration would reduce substrate delivery and metabolite and heat removal to and from active skeletal muscles during prolonged exercise in the heat. A second aim was to examine the effects of dehydration on fuel utilisation across the exercising leg and identify factors related to fatigue. 2 Seven cyclists performed two cycle ergometer exercise trials in the heat (35°C; 61 ± 2% of maximal oxygen consumption rate, V  O 2,max), separated by 1 week. During the first trial (dehydration, DE), they cycled until volitional exhaustion (135 ± 4 min, mean ±s.e.m.), while developing progressive DE and hyperthermia (3.9 ± 0.3% body weight loss and 39.7 ± 0.2°C oesophageal temperature, Toes). On the second trial (control), they cycled for the same period of time maintaining euhydration by ingesting fluids and stabilising Toes at 38.2 ± 0.1°C. 3 After 20 min of exercise in both trials, leg blood flow (LBF) and leg exchange of lactate, glucose, free fatty acids (FFA) and glycerol were similar. During the 20 to 135 ± 4 min period of exercise, LBF declined significantly in DE but tended to increase in control. Therefore, after 120 and 135 ± 4 min of DE, LBF was 0.6 ± 0.2 and 1.0 ± 0.3 l min−1 lower (P < 0.05), respectively, compared with control. 4 The lower LBF after 2 h in DE did not alter glucose or FFA delivery compared with control. However, DE resulted in lower (P < 0.05) net FFA uptake and higher (P < 0.05) muscle glycogen utilisation (45%), muscle lactate accumulation (4.6‐fold) and net lactate release (52%), without altering net glycerol release or net glucose uptake. 5 In both trials, the mean convective heat transfer from the exercising legs to the body core ranged from 6.3 ± 1.7 to 7.2 ± 1.3 kJ min−1, thereby accounting for 35‐40 % of the estimated rate of heat production (∼18 kJ min−1). 6 At exhaustion in DE, blood lactate values were low whereas blood glucose and muscle glycogen levels were still high. Exhaustion coincided with high body temperature (∼40°C). 7 In conclusion, the present results demonstrate that reductions in exercising muscle blood flow with dehydration do not impair either the delivery of glucose and FFA or the removal of lactate during moderately intense prolonged exercise in the heat. However, dehydration during exercise in the heat elevates carbohydrate oxidation and lactate production. A major finding is that more than one‐half of the metabolic heat liberated in the contracting leg muscles is dissipated directly to the surrounding environment. The present results indicate that hyperthermia, rather than altered metabolism, is the main factor underlying the early fatigue with dehydration during prolonged exercise in the heat.

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.

Exercise induces the release of heat shock protein 72 from the human brain in vivo

Abstract The present study tested the hypothesis that in response to physical stress the human brain has the capacity to release heat shock protein 72 (Hsp72) in vivo. Therefore, 6 humans (males) cycled for 180 minutes at 60% of their maximal oxygen uptake, and the cerebral Hsp72 response was determined on the basis of the internal jugular venous to arterial difference and global cerebral blood flow. At rest, there was a net balance of Hsp72 across the brain, but after 180 minutes of exercise, we were able to detect the release of Hsp72 from the brain (335 ± 182 ng/min). However, large individual differences were observed as 3 of the 6 subjects had a marked increase in the release of Hsp72, whereas exercise had little effect on the cerebral Hsp72 balance in the remaining 3 subjects. Given that cerebral blood flow was unchanged during exercise compared with values obtained at rest, it is unlikely that the cerebral Hsp72 release relates to necrosis of specific cells within the brain. These data demonstrate that the human brain is able to release Hsp72 in vivo in response to a physical stressor such as exercise. Further study is required to determine the biological significance of these observations.

Fluid balance in exercise dehydration and rehydration with different glucose-electrolyte drinks

SummaryAfter exercise dehydration (3% of body weight) the restoration of water and electrolyte balance was followed in 6 male subjects. During a 2 h rest period after exercise, a drink of one of four solutions was given as 9×300 ml portions at 15 min intervals: control (C-drink), high potassium (K-drink), high sodium (Na-drink) or high sugar (S-drink). An exercise test (submaximal and supramaximal work) was performed before dehydration and after rehydration. Dehydration reduced plasma volume by 16%, a process reversed on resting even before fluid ingestion began, due to release of water accumulated in the muscles during exercise. After 2 h rehydration, plasma volume was above the initial resting value with all 4 drinks. The final plasma volumes after the Na-drink (+14%) and C-drink (+9%) were significantly higher than after the K- and S-drinks. The Na-drink favoured filling of the extracellular compartment, whereas the K- and S-drinks favoured intracellular rehydration. In spite of the higher than normal plasma volume after rehydration, mean heart rate during the submaximal test was 10 bpm higher after rest and rehydration than in the initial test, and was not different between the drinks. The amount of work which could be performed in the supramaximal test (105%