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.     

Regional blood flow changes in response to thermal stimulation of the brain and spinal cord in the Pekin duck

Summary In conscious Pekin ducks, carotid and sciatic blood flows, respiratory rate, core and skin temperatures were measured during selective thermal stimulations of the spinal cord and rostral brain stem in thermoneutral (20 °C) and warm (32 °C) ambient conditions.At thermoneutral ambient temperature selective heating of the spinal cord by 2–3 °C (to 43–44 °C) increased the carotid blood flow by 138% and the sciatic blood flow by 46%. Increase in blood flows was correlated with increased breathing rate and beak and web skin temperatures.Selective cooling of the spinal cord at warm ambient temperatures and panting reduced the blood flow in both arteries and decreased the breathing rate.Heating or cooling of the brain stem showed generally very weak but otherwise similar responses as thermal stimulation of the spinal cord. In one duck out of six there was a marked effect on regional blood flow during brain stimulation.The results show that thermal stimulation of the spinal cord exerts a marked influence on regional blood flow important in thermoregulation, whereas the lower brain stem shows only a weak thermosensitivity, and stimulation caused only small cardiovascular changes of no major consequence in thermoregulation.     

Peri-OVLT E-series prostaglandins and core temperature do not increase after intravenous IL-1beta in pregnant rats.

Rats have an attenuated febrile response to endogenous pyrogen near the term of pregnancy. Given the fundamental role of E-series prostaglandins (PGEs) in mediating the febrile response to blood-borne endogenous pyrogen, the present experiments were carried out to determine whether PGEs increase in the area surrounding the organum vasculosum laminae terminalis (peri-OVLT) of near-term pregnant (P) rats as in nonpregnant (NP) rats after intravenous (iv) administration of recombinant rat interleukin-1beta (rrIL-1beta). Core temperature was measured by telemetry and peri-OVLT interstitial fluid was sampled in 12 NP and 12 P chronically instrumented, Sprague-Dawley rats by microdialysis for determination of total PGEs by radioimmunoassay. Basal core temperatures were higher in NP compared with P rats (NP 37.9 degrees C +/- 0.5, P 36.9 degrees C +/- 0.4; P < 0.05), but basal peri-OVLT PGEs were similar in both groups (NP 260 +/- 153 pg/ml, P 278 +/- 177 pg/ml; P =not significant). Intravenous administration of rrIL-1beta to NP rats produced a significant increase in core temperature with a latency, magnitude, and duration of 10 min, 0.87 degrees C, and at least 170 min, respectively; peri-OVLT PGEs were increased significantly by 30 min and averaged 270% above basal levels throughout the experiment. In P rats, however, neither core temperature nor peri-OVLT PGEs increased significantly after iv administration of rrIL-1beta. Intravenous administration of vehicle did not significantly alter core temperature or peri-OVLT PGEs in either group of rats. Thus peri-OVLT PGEs do not increase in P rats as they do in NP rats after iv administration of rrIL-1beta. The mechanism of this interesting component of the maternal adaptation to pregnancy, which likely plays a major role in mediating the attenuated febrile response to endogenous pyrogen near the term of pregnancy, warrants further investigation.     

Ambient thermal conditions and thermoregulatory mechanisms in fever in rabbits

At ambient temperatures 10 degrees C, 20 degrees C, 30 degrees C, and 40 degrees C the influence of heat dissipation on the thermoregulatory mechanisms in rabbits with fever was investigated. Temperature of the brain (TBr-accuracy +/- 0.05 degree C) temperature of the nasal mucosa (TN) and temperature of the ear pinna (TAU-accuracy +/- 0.5 degree C) were measured in freely moving rabbits. Changes of conditions of heat dissipation were produced by: preventing heat dissipation by convection and radiation by putting ear-pads on the ear pinnae, high humidity of air for blocking of heat loss through evaporation, and facilitation of heat dissipation through shearing of the fur. The changes of the ambient thermal conditions as well as of the ability of heat dissipation were followed by changes in the dynamics of functions of the remaining (effective) thermoregulatory mechanisms in the rabbits. Thus despite changed thermal conditions of the environment, the TBr of the rabbits with fever was stabilized at a similar level.     

A study of the variability in the febrile responses of rabbits to endogenous pyrogen

The range of body temperature increases elicited by a standard dose of endogenous pyrogen (0.5 ml/kg iv) was examined in a population of 26 male New Zealand White rabbits. Although the mean maximum increase in rectal temperature was 0.88 +/- 0.06 degree C (SE), individual responses varied from 0.4 degree to 1.5 degree C. Three representative animals that responded to the standard dose of pyrogen with small, intermediate, and large febrile responses were selected and challenged with the same dose of pyrogen on eight separate occasions, and the variability of these responses was examined. There was little variability within the characteristic responses of any particular animal to the repeated challenges. The variability of the febrile responses elicited by both intravenous and intracerebroventricular administration of the same pyrogen was examined and compared using another group of 11 rabbits. The variability in response to the intravenous route was similar to that found in the larger population, whereas the variation in response to the intracerebroventricular route was smaller, and all 11 animals had fevers that were greater than 1 degrees C. It is concluded that the variability of the febrile responses of rabbits to intravenous pyrogen was due to differences between individual sensitivities of animals to the intravenously administered pyrogen. This difference in sensitivity may be due to a difference in the amount of pyrogen that reaches the putative receptor sites, or to a difference in the density or effectiveness of receptor sites in translating the pyrogenic stimulus into a fever response.     

Control of panting in the desert iguana: roles for peripheral temperatures and the effect of dehydration

Although it is generally held that panting is a physiological mechanism for the regulation of brain temperature during heat stress, a number of studies have pointed to the importance of peripheral input for the initiation of the panting response in a variety of animals. By presenting ambient heat loads of 47 degrees, 54 degrees, 58 degrees, and 65 degrees C, and measuring skin, ear and core temperatures of the desert iguana, Dipsosaurus dorsalis, at the onset of panting, we found that the skin temperature at panting onset was independent of ambient heat load. This suggests that skin (peripheral) temperature is the body temperature on which the central thermoregulatory center cues to initiate thermal panting. Peripheral temperature control of panting was retained when the plasma osmolality of the desert iguana was increased by 100 mOsm/kg H2O to simulate dehydration. Dehydration to 80% initial body weight (IBW) resulted in a progressive increase in panting threshold (skin) from 42 degrees C for untreated lizards to 42.5 degrees C at 90% IBW to 43.3 degrees C at 80% IBW. Injection of 80% IBW lizards with a volume of 10 mM NaCl equivalent to weight loss resulted in a decrease in panting threshold to 40.8 degrees C. Injection with 1% body weight 3000 mM NaCl produced a dramatic increase in panting threshold to 45.9 degrees C. These data suggest that the desert iguana responds to dehydration by elevating panting threshold, thus promoting water conservation. These data also suggest that changes in plasma osmolality may be involved in the "setting" of panting threshold.     

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.     

The effect of low ambient temperature on the febrile responses of rats to semi-purified human endogenous pyrogen

The febrile responses of Sprague-Dawley rats to semi-purified human endogenous pyrogen were studied at a thermoneutral ambient temperature (26 degrees C) and in the cold (3 degrees C). It was found that while rats developed typical monophasic febrile responses at thermoneutrality, febrile responses were absent in the cold-exposed rats. Experiments were conducted to determine whether this lack of febrile responses in cold-exposed rats was due to an inability of these animals to generate or retain heat in the cold. Thermogenesis and vasoconstriction were stimulated in cold-exposed rats by selectively cooling the hypothalamus, using chronically implanted thermodes. It was shown that, using this stimulus, metabolic rate could be increased by more than 50 percent and body temperature could be driven up at a rate of 5 degrees C/hour in rats exposed to the cold. Therefore, it was concluded that the lack of febrile responses of cold-exposed rats to pyrogen is in no way due to a physical or physiological inability to retain heat. Instead, it appears that in some manner cold exposure suppresses the sensitivity or responsiveness of the rat to pyrogenic stimuli.     

Panting in reindeer (Rangifer tarandus)

Two winter-insulated Norwegian reindeer (Rangifer tarandus tarandus) were exposed to air temperatures of 10, 20, 30, and 38 degrees C while standing at rest in a climatic chamber. The direction of airflow through nose and mouth, and the total and the nasal minute volumes, respectively, were determined during both closed- and open-mouth panting. The animals alternated between closed- and open-mouth panting, but the proportion of open-mouth panting increased with increasing heat load. The shifts from closed- to open-mouth panting were abrupt and always associated with a rise in respiratory frequency and respiratory minute volume. During open-mouth panting, the direction of airflow was bidirectional in both nose and mouth, but only 2.4 +/- (SD) 1.1% of the air was routed through the nose. Estimates suggest that the potential for selective brain cooling is markedly reduced during open-mouth panting in reindeer as a consequence of this airflow pattern.     

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.     

Physical versus pharmacological counter-measures. Studies on febrile rabbits

128 experiments were carried out on febrile rabbits at air temperatures of 8, 18, 24 and 30 degrees C in order to analyze the thermoregulatory effects and mechanisms of physical and/or pharmacological counter-measures. Fever was achieved by injection of 0.1 micrograms Salmonella typhi endotoxin (LPS)/kg into an ear vein. As the pharmacological counter-measure, injections of acetylsalicylic acid (ASA) into an ear vein were chosen. For the physical counter-measure, cooling thermodes (5 degrees C) were constructed for the abdominal skin, for the ear and for the rectum. ASA injections had no effect on the first fever maximum, even if applied 20 to 60 min before the LPS injection, but eliminated the second fever maximum. Of course, the additional hyperthermia observed at 30 degrees C ambient temperature could not be eliminated by the injections. On the other hand, cooling procedures can obviously not affect the pyrogen-induced temperature increase, but reduce the hyperthermic effect of a higher ambient temperature. Rectal cooling was more effective than ear or abdominal skin cooling. Abdominal cooling evoked an increase in metabolic heat production. Application of combined physical and pharmacological counter-measures achieved the strongest and quickest reduction of the second maximum, whereas the first maximum was not affected, as in all other experiments. The study emphasizes the necessity of taking into account the time course of the effector mechanisms in order to discriminate between hyperthermic and febrile components of temperature increase. In the initial phase cooling measures would evoke unwanted regulatory responses of the effectors, whereas during the second febrile maximum they would achieve a quicker reduction of core temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of ambient temperature on beta-adrenergic responsiveness in rats.

The responses of tail skin and colonic temperatures of female rats to ambient temperatures of 20, 22, 24, 26, 28, and 30 degrees C were measured. Within this range, colonic temperature was stable while tail skin temperature increased linearly with increasing ambient temperature. Administration of the beta-adrenergic agonist, d,l-isoproterenol, at 10.0, 25.0, and 62.5 micrograms/kg, sc, at each ambient temperature was accompanied by increases in tail skin and colonic temperatures that were dependent on both the dose of isoproterenol administered and the ambient temperature. The integrated responses of tail skin temperature following administration of the three doses of isoproterenol were maximal at an ambient temperature of 26 degrees C while the integrated responses of colonic temperature were maximal at 30 degrees C. The results suggest that tests of beta-adrenergic responsiveness using this technique should be performed at an ambient temperature of 26 degrees C for maximal sensitivity.     

An infrared thermographic study of surface temperature in the euthermic woodchuck (Marmota monax).

Surface temperatures were measured in euthermic woodchucks (Marmota monax) using infrared thermography across a range of ambient temperatures from -10 degrees C to 32 degrees C. The woodchuck keeps surface temperature of the peripalpebral region uniformly high, while head and body surfaces change proportionally with ambient temperature. When ambient temperature was below 0 degrees C, all surface temperatures increased which prevents freezing. At no point did the animals appear to be unable to regulate heat exchange. This species appears to be especially well adapted to the higher temperatures it encounters in its range. Vasomotion in the feet and to a lesser extent in the pinnae was used to regulate heat loss. At ambient temperature of 32 degrees C, mean temperatures of nose surfaces were 0.2 degrees C and 0.3 degrees C less than ambient temperature suggesting a type of counter current cooling mechanism may be present.     

Observations on the effect of salicylate in fever and the regulation of body temperature against cold.

Prostaglandins appear to be mediators, within the hypothalamus, of heat production and conservation during fever. We have investigated a possible role of prostaglandins in the nonfebrile rabbit during thermoregulation in the cold. Shorn rabbits were placed in an environment of 20 degrees C, and rectal and ear skin temperatures, shivering and respiratory rates were measured. A continuous intravenous infusion of leucocyte pyrogen was given to establish a constant fever of approximately 1 degree C, and after observation of a stable febrile temperature for 90 min, a single injection of 300 mg of sodium salicylate, followed by a 1.5 mg/min infusion was then given. After the salicylate infusion was begun, rectal temperature began to fall, and reached nonfebrile levels within 90 min. Shivering activity ceased, respiratory rates increased, and in two animals, ear skin temperature increased. When these same rabbits were placed in an environment of 10 degrees C, at a time they were not febrile, and an identical amount of salicylate was given, rectal and ear skin temperatures, shivering and respiratory rates did not change. These results indicate that prostagladins do not appear to be involved in heat production and conservation in the nonfebrile rabbit.     

Mechanism of action of physical antipyresis in the rat

To study the mechanism of action of physical antipyresis, core temperature was measured in two groups of rats in which heat loss was increased by cold exposure and by cooling an inferior cava heat exchanger, respectively, both before and after infection with Salmonella enteritidis. Cold exposure did not influence core temperature. On the other hand, cooling the heat exchanger caused a fall in core temperature of approximately 0.7 degree C, to 37 degrees C in normothermia and to 38.5 degrees C 24 h after the infection. These lower core temperatures were then regulated against any further increase in heat loss until the thermoregulatory metabolic capacity of the animals was exhausted and a hypothermia developed. It is concluded that in infectious fever the threshold temperature of shivering increases as much as core temperature. Furthermore it is suggested that physical antipyresis, such as sponging with tepid water, induces a moderate but regulated fall in temperature to about the threshold of shivering and that its efficacy may increase with ambient temperature.     

Competition for cool nasal blood between trunk and brain in hyperthermic goats

An influence of brain and trunk temperatures controlled independently of each other by means of artificial heat exchangers, on the intensity of natural selective brain cooling (SBC) was studied in 6 conscious goats. Intensity of SBC was markedly enhanced by increasing brain temperature. On the other hand, a rise of trunk temperature with the cerebral temperature clamped at 39 degrees C or 40 degrees C, reduced SBC intensity in spite of a simultaneous increase in the respiratory evaporative heat loss. When brain temperature was clamped at 41 degrees C, the magnitude of SBC was essentially independent of trunk temperature. These results suggest that during hyperthermia a competition exists between trunk and brain for cool nasal blood.     

Scrotal heating stimulates panting and reduces body temperature similarly in febrile and non-febrile rams (Ovis aries)

It is known that heating the ram scrotum stimulates heat loss resulting in a decrease in body temperature and that during fever core temperature increases, but local scrotal thermoeffectors operate to maintain normal scrotal temperature. We have investigated whether scrotal warming influences core body temperature and the panting effector during fever generation. We measured rectal temperature, intrascrotal temperature, scrotal skin temperature and respiratory frequency in four adult Merino rams following intravascular injection of saline or lipopolysaccharide at an ambient temperature of 18-20 degrees C while scrotal skin temperature was maintained at 33 degrees C or elevated to 41 degrees C. Compared to maintaining normal scrotal temperature, heating the scrotum increased respiratory frequency and reduced rectal temperature by a similar amount following LPS as following saline. Fever was associated with decreased respiratory frequency compared to saline at both 33 and 41 degrees C scrotal temperature, suggesting that the fever was generated mainly by decreasing respiratory heat loss. We conclude that scrotal thermal afferent stimulation resulted in an offset for the set-point of body temperature regulation in both normothermic and febrile rams.     

Perfusion of the septum of the rabbit with vasopressin antiserum enhances endotoxin fever

The septal region of the brains of conscious, adult, male New Zealand White rabbits were perfused by means of a push-pull system before and after an intravenous administration of bacterial pyrogen extracted from Salmonella abortus equi. Perfusion of the septal area with sucrose solution (260 mM) had no significant effect on the resulting fever (1.13 +/- 0.09 degrees C) when compared to a control fever without the push-pull perfusion (1.06 +/- 0.12 degrees C). Arginine vasopressin (AVP) added to the perfusing solution (20 micrograms/ml) caused a significant attenuation of the fever (0.81 +/- 0.20 degrees C). An antiserum specific to AVP when added to the perfusing solution resulted in a fever which was significantly greater (2.38 +/- 0.13 degrees C) than the control. Radioimmunoassay of perfusates collected from the control perfusions before and during fever showed that, as the body temperature rose in response to the pyrogen, the level of AVP in the perfusate collected from the septal area decreased. These results provide further evidence that AVP may act in the septal area of the brain to modulate the febrile response.     

Modulation of plasma biotin in the fowl (Gallus domesticus) by oestrogen and ambient temperature.

1. Exposure of laying hens to elevated ambient temperatures (30-40 degrees C) resulted in a significant increase in the biotin concentrations in plasma and egg yolk. 2. Exogenous oestrogen administration to immature pullets increased plasma biotin three-fold. The increase was six-fold when the birds were simultaneously exposed to an ambient temperature of 35 degrees C. 3. It is proposed that ambient temperature affects the balance between thyroid and ovarian hormones resulting in increased circulating levels of biotin and deposition of the vitamin in egg yolk.     

Oxygen consumption of brown noddy (Anous stolidus) embryos in a quasiequilibrium state at lowered ambient temperatures

1. The oxygen consumption (MO2) of the semi-precocial Brown Noddy embryos at different stages of development was measured at 36 degrees C and again after 5-hr exposure to lowered ambient temperatures (30 and 32 degrees C). 2. The MO2 measured in a quasiequilibrium state was equal to the value predicted by a temperature coefficient of 2. 3. In contrast to precocial chickens, the semi-precocial Noddy had no apparent metabolic response to cooling before hatching.