A test of biochemical symmorphosis in a heterothermic tissue: bluefin tuna white muscle

Selective brain cooling (SBC) is defined as a brain temperature cooler than the temperature of arterial blood from the trunk. Surrogate measures of arterial blood temperature have been used in many published studies on SBC. The use of a surrogate for arterial blood temperature has the potential to confound proper identification of SBC. We have measured brain, carotid blood, and rectal temperatures in conscious sheep exposed to 40, 22, and 5 degrees C. Rectal temperature was consistently higher than arterial blood temperature. Brain temperature was consistently cooler than rectal temperature during all exposures. Brain temperature only fell below carotid blood temperature during the final few hours of 40 degrees C exposure and not at all during the 5 degrees C exposure. Consequently, using rectal temperature as a surrogate for arterial blood temperature does not provide a reliable indication of the status of the SBC effector. We also show that rapid suppression of SBC can result if the animals are disturbed.     

Dehydration increases the magnitude of selective brain cooling independently of core temperature in sheep

By cooling the hypothalamus during hyperthermia, selective brain cooling reduces the drive on evaporative heat loss effectors, in so doing saving body water. To investigate whether selective brain cooling was increased in dehydrated sheep, we measured brain and carotid arterial blood temperatures at 5-min intervals in nine female Dorper sheep (41 +/- 3 kg, means +/- SD). The animals, housed in a climatic chamber at 23 degrees C, were exposed for nine days to a cyclic protocol with daytime heat (40 degrees C for 6 h). Drinking water was removed on the 3rd day and returned 5 days later. After 4 days of water deprivation, sheep had lost 16 +/- 4% of body mass, and plasma osmolality had increased from 290 +/- 8 to 323 +/- 9 mmol/kg (P < 0.0001). Although carotid blood temperature increased during heat exposure to similar levels during euhydration and dehydration, selective brain cooling was significantly greater in dehydration (0.38 +/- 0.18 degrees C) than in euhydration (-0.05 +/- 0.14 degrees C, P = 0.0008). The threshold temperature for selective brain cooling was not significantly different during euhydration (39.27 degrees C) and dehydration (39.14 degrees C, P = 0.62). However, the mean slope of lines of regression of brain temperature on carotid blood temperature above the threshold was significantly lower in dehydrated animals (0.40 +/- 0.31) than in euhydrated animals (0.87 +/- 0.11, P = 0.003). Return of drinking water at 39 degrees C led to rapid cessation of selective brain cooling, and brain temperature exceeded carotid blood temperature throughout heat exposure on the following day. We conclude that for any given carotid blood temperature, dehydrated sheep exposed to heat exhibit selective brain cooling up to threefold greater than that when euhydrated.     

Guttural pouches, brain temperature and exercise in horses

Selective brain cooling (SBC) is defined as the lowering of brain temperature below arterial blood temperature. Artiodactyls employ a carotid rete, an anatomical heat exchanger, to cool arterial blood shortly before it enters the brain. The survival advantage of this anatomy traditionally is believed to be a protection of brain tissue from heat injury, especially during exercise. Perissodactyls such as horses do not possess a carotid rete, and it has been proposed that their guttural pouches serve the heat-exchange function of the carotid rete by cooling the blood that traverses them, thus protecting the brain from heat injury. We have tested this proposal by measuring brain and carotid artery temperature simultaneously in free-living horses. We found that despite evidence of cranial cooling, brain temperature increased by about 2.5 degrees C during exercise, and consistently exceeded carotid temperature by 0.2-0.5 degrees C. We conclude that cerebral blood flow removes heat from the brain by convection, but since SBC does not occur in horses, the guttural pouches are not surrogate carotid retes.     

Absence of selective brain cooling in unrestrained baboons exposed to heat

To test whether baboons are capable of implementing selective brain cooling, we measured, every 5 min, the temperature in their hypothalamus, carotid arterial bloodstream, and abdominal cavity. The baboons were unrestrained and exposed to 22 degrees C for 7 days and then to a cyclic environment with 15 degrees C at night and 35 degrees C during the day for a further 7 days. During the latter 7 days some of the baboons also were exposed to radiant heat during the day. For three days, during heat exposure, water was withheld. At no time was the hypothalamus cooler than carotid arterial blood, despite brain temperatures above 40 degrees C. With little variation, the hypothalamus was consistently 0.5 degrees C warmer than arterial blood. At high body temperatures, the hypothalamus was sometimes cooler than the abdomen. Abdominal temperature was more variable than arterial blood and tended to exceed arterial blood temperature at higher body temperatures. Hypothalamic temperature cooler than a warm abdomen is not evidence for selective brain cooling. In species that can implement selective brain cooling, the brain is most likely to be cooler than carotid arterial blood when an animal is hyperthermic, during heat exposure, and also dehydrated and undisturbed by human presence. When we exposed baboons to high ambient temperatures while they were water deprived and undisturbed, they never implemented selective brain cooling. We conclude that baboons cannot implement selective brain cooling and can find no convincing evidence that any primate species can do so.     

The contribution of carotid rete variability to brain temperature variability in sheep in a thermoneutral environment

The degree of variability in the temperature difference between the brain and carotid arterial blood is greater than expected from the presumed tight coupling between brain heat production and brain blood flow. In animals with a carotid rete, some of that variability arises in the rete. Using thermometric data loggers in five sheep, we have measured the temperature of arterial blood before it enters the carotid rete and after it has perfused the carotid rete, as well as hypothalamic temperature, every 2 min for between 6 and 12 days. The sheep were conscious, unrestrained, and maintained at an ambient temperature of 20-22 degrees C. On average, carotid arterial blood and brain temperatures were the same, with a decrease in blood temperature of 0.35 degrees C across the rete and then an increase in temperature of the same magnitude between blood leaving the rete and the brain. Rete cooling of arterial blood took place at temperatures below the threshold for selective brain cooling. All of the variability in the temperature difference between carotid artery and brain was attributable statistically to variability in the temperature difference across the rete. The temperature difference between arterial blood leaving the rete and the brain varied from -0.1 to 0.9 degrees C. Some of this variability was related to a thermal inertia of the brain, but the majority we attribute to instability in the relationship between brain blood flow and brain heat production.     

Brain thermal inertia,but no evidence for selective brain cooling,in free-ranging western grey kangaroos (<Emphasis Type="Italic">Macropus fuliginosus</Emphasis>)

Marsupials reportedly can implement selective brain cooling despite lacking a carotid rete. We measured brain (hypothalamic) and carotid arterial blood temperatures every 5 min for 5, 17, and 63 days in spring in three free-living western grey kangaroos. Body temperature was highest during the night, and decreased rapidly early in the morning, reaching a nadir at 10:00. The highest body temperatures recorded occurred sporadically in the afternoon, presumably associated with exercise. Hypothalamic temperature consistently exceeded arterial blood temperature, by an average 0.3°C, except during these afternoon events when hypothalamic temperature lagged behind, and was occasionally lower than, the simultaneous arterial blood temperature. The reversal in temperatures resulted from the thermal inertia of the brain; changes in the brain to arterial blood temperature difference were related to the rate of change of arterial blood temperature on both heating and cooling (P < 0.001 for all three kangaroos). We conclude that these data are not evidence for active selective brain cooling in kangaroos. The effect of thermal inertia on brain temperature is larger than might be expected in the grey kangaroo, a discrepancy that we speculate derives from the unique vascular anatomy of the marsupial brain.     

Ventilatory acclimatization to hypoxia is not dependent on arterial hypoxemia

Goats were prepared so that one carotid body (CB) could be perfused with blood in which the gas tensions could be controlled independently from the blood perfusing the systemic arterial system, including the brain. Since one CB is functionally adequate, the nonperfused CB was excised. To determine whether systemic arterial hypoxemia is necessary for ventilatory acclimatization to hypoxia (VAH), the CB was perfused with hypoxic normocapnic blood for 6 h [means +/- SE: partial pressure of carotid body O2 (PcbO2), 40.6 +/- 0.3 Torr; partial pressure of carotid body CO2 (PcbCO2), 38.8 +/- 0.2 Torr] while the awake goat breathed room air to maintain systemic arterial normoxia. In control periods before and after CB hypoxia the CB was perfused with hyperoxic normocapnic blood. Changes in arterial PCO2 (PaCO2) were used as an index of changes in ventilation. Acute hypoxia (0.5 h of hypoxic perfusion) resulted in hyperventilation sufficient to reduce average PaCO2 by 6.7 Torr from control (P less than 0.05). Over the subsequent 5.5 h of hypoxic perfusion, average PaCO2 decreased further, reaching 4.8 Torr below that observed acutely (P less than 0.05). Acute CB hyperoxic perfusion (20 min) following 6 h of hypoxia resulted in only partial restoration of PaCO2 toward control values; PaCO2 remained 7.9 Torr below control (P less than 0.05). The progressive hyperventilation that occurred during and after 6 h of CB hypoxia with concomitant systemic normoxia is similar to that occurring with total body hypoxia. We conclude that systemic (and probably brain) hypoxia is not a necessary requisite for VAH.     

Temperature difference between the body core and arterial blood supplied to the brain during hyperthermia or hypothermia in humans

 A vascular heat transfer model is developed to simulate temperature decay along the carotid arteries in humans, and thus, to evaluate temperature differences between the body core and arterial blood supplied to the brain. Included are several factors, including the local blood perfusion rate, blood vessel bifurcation in the neck, and blood vessel pairs on both sides of the neck. The potential for cooling blood in the carotid artery by countercurrent heat exchange with the jugular veins and by radial heat conduction to the neck surface was estimated. Cooling along the common and internal carotid arteries was calculated to be up to 0.87 °C during hyperthermia by high environmental temperatures or muscular exercise. This model was also used to evaluate the feasibility of lowering the brain temperature effectively by placing ice pads on the neck and head surface or by wearing cooling garments during hypothermia treatment for brain injury or other medical conditions. It was found that a 1.1 °C temperature drop along the carotid arteries is possible when the neck surface is cooled to 0 °C. Thus, the body core temperature may not be a good indication of the brain temperature during hyperthermia or hypothermia. Received: 10 January 2002 / Accepted: 7 May 2002 This research was supported by a UMBC Summer Faculty Fellowship.     

Modulation of arterial baroreflex control of heart rate by skin cooling and heating in humans.

The purpose of this study was to examine the effects of skin cooling and heating on the heart rate (HR) control by the arterial baroreflex in humans. The subjects were 15 healthy men who underwent whole body thermal stress (esophageal temperatures, approximately 36.8 and approximately 37.0 degrees C; mean skin temperatures, approximately 26.4 and approximately 37.7 degrees C, in skin cooling and heating, respectively) produced by a cool or hot water-perfused suit during supine rest. The overall arterial baroreflex sensitivity in the HR control was calculated from spontaneous changes in beat-to-beat arterial pressure and HR during normothermic control and thermal stress periods. The carotid baroreflex sensitivity was evaluated from the maximum slope of the HR response to changes in carotid distending pressure, calculated as mean arterial pressure minus neck pressure. The overall arterial baroreflex sensitivity at existing arterial pressure increased during cooling (-1.32 +/- 0.25 vs. -2.13 +/- 0.20 beats. min(-1). mmHg(-1) in the control and cooling periods, respectively, P < 0.05), whereas it did not change significantly during heating (-1.39 +/- 0. 23 vs. -1.40 +/- 0.15 beats. min(-1). mmHg(-1) in the control and heating periods, respectively). Neither the cool nor heat loadings altered the carotid baroreflex sensitivity in the HR control. These results suggest that the sensitivity of HR control by the extracarotid (presumably aortic) baroreflex was augmented by whole body skin cooling, whereas the sensitivities of HR control by arterial baroreflex remain unchanged during mild whole body heating in humans.     

Selective Brain Cooling Reduces Water Turnover in Dehydrated Sheep

In artiodactyls, arterial blood destined for the brain can be cooled through counter-current heat exchange within the cavernous sinus via a process called selective brain cooling. We test the hypothesis that selective brain cooling, which results in lowered hypothalamic temperature, contributes to water conservation in sheep. Nine Dorper sheep, instrumented to provide measurements of carotid blood and brain temperature, were dosed with deuterium oxide (D₂O), exposed to heat for 8 days (40◦C for 6-h per day) and deprived of water for the last five days (days 3 to 8). Plasma osmolality increased and the body water fraction decreased over the five days of water deprivation, with the sheep losing 16.7% of their body mass. Following water deprivation, both the mean 24h carotid blood temperature and the mean 24h brain temperature increased, but carotid blood temperature increased more than did brain temperature resulting in increased selective brain cooling. There was considerable inter-individual variation in the degree to which individual sheep used selective brain cooling. In general, sheep spent more time using selective brain cooling, and it was of greater magnitude, when dehydrated compared to when they were euhydrated. We found a significant positive correlation between selective brain cooling magnitude and osmolality (an index of hydration state). Both the magnitude of selective brain cooling and the proportion of time that sheep spent selective brain cooling were negatively correlated with water turnover. Sheep that used selective brain cooling more frequently, and with greater magnitude, lost less water than did conspecifics using selective brain cooling less efficiently. Our results show that a 50kg sheep can save 2.6L of water per day (~60% of daily water intake) when it employs selective brain cooling for 50% of the day during heat exposure. We conclude that selective brain cooling has a water conservation function in artiodactyls.     

Baroreflex control of muscle sympathetic nerve activity during skin surface cooling.

Skin surface cooling improves orthostatic tolerance through a yet to be identified mechanism. One possibility is that skin surface cooling increases the gain of baroreflex control of efferent responses contributing to the maintenance of blood pressure. To test this hypothesis, muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate were recorded in nine healthy subjects during both normothermic and skin surface cooling conditions, while baroreflex control of MSNA and heart rate were assessed during rapid pharmacologically induced changes in arterial blood pressure. Skin surface cooling decreased mean skin temperature (34.9 +/- 0.2 to 29.8 +/- 0.6 degrees C; P < 0.001) and increased mean arterial blood pressure (85 +/- 2 to 93 +/- 3 mmHg; P < 0.001) without changing MSNA (P = 0.47) or heart rate (P = 0.21). The slope of the relationship between MSNA and diastolic blood pressure during skin surface cooling (-3.54 +/- 0.29 units.beat(-1).mmHg(-1)) was not significantly different from normothermic conditions (-2.94 +/- 0.21 units.beat(-1).mmHg(-1); P = 0.19). The slope depicting baroreflex control of heart rate was also not altered by skin surface cooling. However, skin surface cooling shifted the "operating point" of both baroreflex curves to high arterial blood pressures (i.e., rightward shift). Resetting baroreflex curves to higher pressure might contribute to the elevations in orthostatic tolerance associated with skin surface cooling.     

Adaptive heterothermy and selective brain cooling in arid-zone mammals

Adaptive heterothermy and selective brain cooling are regarded as important thermal adaptations of large arid-zone mammals. Adaptive heterothermy, a process which reduces evaporation by storing body heat, ought to be enhanced by ambient heat load and by water deficit, but most mammals studied fail to show at least one of those attributes. Selective brain cooling, the reduction of brain temperature below arterial blood temperature, is most evident in artiodactyls, which possess a carotid rete, and traditionally has been considered to protect the brain during hyperthermia. The development of miniature ambulatory data loggers for recording body temperature allows the temperatures of free-living wild mammals to be measured in their natural habitats. All the African ungulates studied so far, in their natural habitats, do not exhibit adaptive heterothermy. They have low-amplitude nychthemeral rhythms of temperature, with mean body temperature over the night exceeding that over the day. Those with carotid retes (black wildebeest, springbok, eland) employ selective brain cooling but zebra, without a rete, do not. None of the rete ungulates, however, seems to employ selective brain cooling to prevent the brain overheating during exertional hyperthermia. Rather, they use it at rest, under moderate heat load, we believe in order to switch body heat loss from evaporative to non-evaporative routes.     

Wave reflection augments central systolic and pulse pressures during facial cooling

Cardiovascular events are more common in the winter months, possibly because of hemodynamic alterations in response to cold exposure. The purpose of this study was to determine the effect of acute facial cooling on central aortic pressure, arterial stiffness, and wave reflection. Twelve healthy subjects (age 23 +/- 3 yr; 6 men, 6 women) underwent supine measurements of carotid-femoral pulse wave velocity (PWV), brachial artery blood pressure, and central aortic pressure (via the synthesis of a central aortic pressure waveform by radial artery applanation tonometry and generalized transfer function) during a control trial (supine rest) and a facial cooling trial (0 degrees C gel pack). Aortic augmentation index (AI), an index of wave reflection, was calculated from the aortic pressure waveform. Measurements were made at baseline, 2 min, and 7 min during each trial. Facial cooling increased (P < 0.05) peripheral and central diastolic and systolic pressures. Central systolic pressure increased more than peripheral systolic pressure (22 +/- 3 vs. 15 +/- 2 mmHg; P < 0.05), resulting in decreased pulse pressure amplification ratio. Facial cooling resulted in a robust increase in AI and a modest increase in PWV (AI: -1.4 +/- 3.8 vs. 21.2 +/- 3.0 and 19.9 +/- 3.6%; PWV: 5.6 +/- 0.2 vs. 6.5 +/- 0.3 and 6.2 +/- 0.2 m/s; P < 0.05). Change in mean arterial pressure but not PWV predicted the change in AI, suggesting that facial cooling may increase AI independent of aortic PWV. Facial cooling and the resulting peripheral vasoconstriction are associated with an increase in wave reflection and augmentation of central systolic pressure, potentially explaining ischemia and cardiovascular events in the cold.     

Adaptive thermoregulatory reactions of the rabbit fetus at the end of the intrauterine development

The data of permanent simultaneous registration of electrocardiogram, rectal & brown adipose tissue temperatures of the rabbit foetus have been obtained in chronic experiments. The haemodynamic shift in intensity of maternal-placental and foeto-placental blood flow (by female trental injection) led to a decrease in the foetus rectal temperature (0.33 +/- 0.09 degree C in intact foetus and 0.58 +/- 0.27 degree C in retarded foetus, p < 0.05). Both foetuses reacted by rectal temperature decrease (0.65 +/- 0.28 & 0.68 +/- 0.31 degree C, respectively) during immobilisation (by foetus arduan injection). Thus in both series of experimental cooling of foetus, brown fat activation was similar in intact foetus (approximately 53%), but did not change in growth retardation foetus--as a result of its tissue functional immaturity, probably.     

Effects of hypothermia on rat brain pHi and phosphate metabolite regulation by 31P-NMR

The effects of arterial alphastat regulation on brain intracellular pH (pHi) and several phosphate metabolites were assessed in anesthetized rats during hypothermia (28.6 +/- 0.2 degrees C) and normothermia (36.2 +/- 0.2 degrees C) by using 31P high-field (8.5 T) nuclear magnetic resonance (NMR). There were significant differences in pHi and metabolite ratios at the two temperatures under conditions of equal minute ventilation. During hypothermia, the brain pHi was 0.09 U higher, the phosphocreatine-to-inorganic phosphate (PCR/Pi) ratio 49% larger, and Pi-to-ATP 20% lower than at normothermia. These changes were fully reversible on warming the animal. The change in brain pHi/temperature was -0.011U/degrees C (95% confidence interval -0.007 to -0.016). The brain's ability to regulate its pHi and phosphate metabolism during hypercapnic acid-base stress was studied by using 10% CO2 ventilation. Hypothermic rats showed a larger fall in brain pHi (0.145 +/- 0.01 U, 7.15-7.01) with 10% CO2 than normothermic rats (0.10 +/- 0.02 U, 7.06-6.96). Similarly ventilated rats had a larger fall in arterial pH with 10% CO2 at hypothermia (0.36 +/- 0.04 U) than normothermia (0.24 +/- 0.01 U), so the delta brain pH/delta arterial pH was the same at both temperatures. The brain PCr-to-Pi ratio decreased approximately 20% during 10% CO2 breathing in both hypothermic and normothermic animals. Brain pHi and metabolite ratios returned to base line 30-50 min after CO2 washout in both groups. In summary, lowering body temperature while maintaining constant ventilation leads to changes in brain pHi and metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise hyperthermia as a factor limiting physical performance: temperature effect on muscle metabolism

The muscle contents of high-energy phosphates and their derivatives [ATP, ADP, AMP, creatine phosphate (CrP), and creatine], glycogen, some glycolytic intermediates, pyruvate, and lactate were compared in 11 dogs performing prolonged heavy exercise until exhaustion (at ambient temperature 20.0 +/- 1.0 degrees C) without and with trunk cooling using ice packs. Without cooling, dogs were able to run for 57 +/- 8 min, and their rectal (Tre) and muscle (Tm) temperatures increased to 41.8 +/- 0.2 and 43.0 +/- 0.2 degrees C, respectively. Compared with noncooling, duration of exercise with cooling was longer by approximately 45% while Tre and Tm at the time corresponding to the end of exercise without cooling were lower by 1.1 +/- 0.2 and 1.2 +/- 0.2 degrees C, respectively. The muscle contents of high-energy phosphates (ATP + CrP) decreased less, the rate of glycogen depletion was lower, and the increases in the contents of AMP, pyruvate, and lactate as well as in the muscle-to-blood lactate ratio were smaller. The muscle content of lactate was positively correlated with Tm. The data indicate that with higher body temperature equilibrium between high-energy phosphate breakdown and resynthesis was shifted to the lower values of ATP and CrP and glycolysis was accelerated. The results suggest that hyperthermia developing during prolonged muscular work exerts an adverse effect on muscle metabolism that may be relevant to limitation of endurance.     

Sweating, hemodynamic responses, and thermal equilibration during hyperthermia in humans

Hyperthermia, to 42 degrees C, for treatment of cancer, was induced 23 times in 13 anesthetized patients utilizing an extracorporeal heat-exchange circuit. Sweating rate over the chest, abdomen, arm and forearm ranged from 0.2 to 0.9 mg sweat X min-1 X cm-2. Cardiac index (CI), stroke volume index (SVI), left ventricular stroke work index, and right ventricular stroke work index initially increased to 221 +/- 12.5, 162 +/- 9.6, 142 +/- 11, and 203 +/- 29% but later fell to 169-173, 113-120, 69, and 148-117% of control, respectively. Heart rate initially rose to 145 +/- 5.9% and then stabilized at 160-162% of control. Pulmonary arterial occlusion pressure and central venous pressure initially fell to 82 +/- 8 and 93 +/- 9% but later rose to 87-102 and 105-120% of control levels, respectively. The hemodynamic response to severe heat stress in anesthetized humans was characterized by peripheral vasodilation accompanied by compensatory increases in heart rate and CI. Ventricular function, as reflected by SVI and CI, declined with continued heat stress, despite reduced afterload and stable or increased filling pressures. Pulmonary arterial temperature rose fastest, followed by the esophageal, rectal, and bladder temperatures, respectively. Jugular bulb temperature also rose rapidly.     

Body temperature changes in dogs exposed to varying effective temperatures

Adult male and female Beagle dogs (eight total) were exposed individually, in series, to each of 23 effective temperatures for a period of 2 hours or until rectal temperature increased 1.1 degrees C. Rectal temperature was measured to the nearest 0.1 degree C by thermistor probes in the pre-test condition (basal temperature) and at each 5-minute interval during the test conditions (effective temperatures between 21.1 degrees C and 34.7 degrees C). The frequency at which dogs displayed a 1.1 degree C rise in rectal temperature was related to the magnitude of the effective temperature. At an effective temperature of 32.6 degrees C or greater, 100% of the dogs displayed a 1.1 degree C rise in rectal temperature. Between an effective temperature of 29.3 degrees C and 31.4 degrees C, some animals displayed a 1.1 degree C rise while others did not. At an effective temperature of 28.4 degrees C or below no animals displayed a 1.1 degree C rise. The mean time necessary for a 1.1 degree C rise was negatively correlated (P less than 0.01) to the magnitude of the effective temperature. The minimum effective temperature necessary to increase rectal temperature by 1.1 degree C in male Beagles (29.6 +/- 1.0 degree C) was not significantly different from females (30.8 +/- 0.4 degrees C).     

REM sleep related increase in brain temperature: a physiologic problem

The roles of metabolic heat production, arterial blood flow and temperature in the genesis of the brain temperature increase related to REM sleep occurrence in several mammalian species are discussed on the basis of available experimental evidence. The experimental data show that only changes in arterial blood flow and temperature consistently underlie the rise in brain temperature in presence (cat) or absence (rabbit) of the carotid rete. The alteration of cardiovascular regulation in REM sleep is the remote cause of such rise. The proximate causes are decrease in carotid blood supply and increase in vertebral blood supply to the brain and related depression of systemic and selective brain cooling.     

The effects of head cooling on endurance and neuroendocrine responses to exercise in warm conditions

The present study investigated the effects of head cooling during endurance cycling on performance and the serotonergic neuroendocrine response to exercise in the heat. Subjects exercised at 75 % VO(2max) to volitional fatigue on a cycle ergometer at an ambient temperature of 29+/-1.0 degrees C, with a relative humidity of approximately 50 %. Head cooling resulted in a 51 % (p<0.01) improvement in exercise time to fatigue and Borg Scale ratings of perceived exertion were significantly lower throughout the exercise period with cooling (p<0.01). There were no indications of peripheral mechanisms of fatigue either with, or without, head cooling, indicating the importance of central mechanisms. Exercise in the heat caused the release of prolactin in response to the rise in rectal temperature. Head cooling largely abolished the prolactin response while having no effect on rectal temperature. Tympanic temperature and sinus skin temperature were reduced by head cooling and remained low throughout the exercise. It is suggested that there is a co-ordinated response to exercise involving thermoregulation, neuroendocrine secretion and behavioural adaptations that may originate in the hypothalamus or associated areas of the brain. Our results are consistent with the effects of head cooling being mediated by both direct cooling of the brain and modified cerebral artery blood flow, but an action of peripheral thermoreceptors cannot be excluded.