A comparison between total body thermosensitivity and local thermosensitivity in mammals and birds

We have investigated how total body thermosensitivity in various mammalian and avian species (mouse, rat, golden hamster, guinea pig, rabbit, dog, goat, pigeon, duck, goose) is related to their respective local thermosensitivities in the hypothalamus, spinal cord and skin. Local and total thermosensitivities were determined by measuring the relationship between the response of one thermoregulatory effector, metabolic heat production, and the appropriate temperature. Local cooling was performed with chronically implanted, water perfused thermodes, and local thermosensitivities were estimated by relating the maximum activation of metabolic heat production to the induced decreases in local temperature. Total body cooling was achieved by means of chronically implanted intravascular heat exchangers or with thermodes inserted into the lower intestinal tract, and total body thermosensitivity was assessed by relating the rise in metabolic heat production to the induced fall in core temperature. These analyses plus previous estimations derived from the literature show total body thermosensitivity in the different species to range from –4.0 to –12.0 W · kg^–1 · °C^–1. We also measured rabbit spinal cord thermosensitivity and guinea pig hypothalamic and spinal cord thermosensitivity; values for local thermosensitivity in other species were derived from the literature. In all species, local thermosensitivities determined as cold sensitivities in the described way were smaller than the corresponding total body core sensitivities. We conclude that thermosensitive structures outside of the investigated thermosensitive areas contribute a major input to the controller of body temperature, particularly in avian species in which hypothalamic thermosensitivity is lacking. This corresponds to observations in several mammalian and one avian species in which local and total body thermosensitivities were dervied from the responses of an autonomic heat defence effector, respiratory evaporative heat loss.     

Hypothalamic thermosensitivity in an Emu,Dromiceius novae-hollandiae

Thermosensitivity of the rostral brainstem was tested in a conscious Emu which had been previously implanted with a hypothalamic perfusion thermode. Hypothalamic warming decreased colonic temperature and cooling increased it. The maximum response to cooling occurred at a hypothalamic temperature of 34.4 °C and was accompanied by visible shivering. Thus in the Emu specific hypothalamic thermosensitivity appears to extend, relative to that in other avian species, further down into the hypothermic range, to some extent resembling the mammalian type of brainstem thermosensitivity.     

The role of spinal thermosensitive structures in the respiratory heat loss during exercise

Summary Two dogs were prepared with spinal thermodes and hypothalamic guide tubes. The spinal thermodes could be used either for measuring the temperature of the peridural space of the spinal cord or for artificially altering this temperature. The hypothalamic guide tube was for measuring hypothalamic temperature. It was found that during exercise the temperature of the spinal cord increased and closely followed the temperature of the working muscles. The temperature of the hypothalamus increased only insignificantly. In a second series of experiments the spinal cord temperature of the same two dogs was artificially altered during exercise and the change in respiratory evaporative heat loss (REHL) was measured. It was found that spinal cord warming increased REHL both at rest and during exercise. At air temperatures of 30° and 32°C the sensitivity to spinal cord warming, as judged from the intercept and slope of calculated regression lines, was unaffected by exercise. At air temperatures of 25° and 27°C the sensitivityto spinal cord warming during exercise was the same as at the higher air temperature.—Spinal cord cooling was unable to inhibit the REHL during exercise. It is therefore concluded from these results that temperature signals generated in the spinal cord are not involved in the control of exercise induced increase in REHL.     

Spinal cord and hypothalamus as core sensors of temperature in the conscious dog

Summary In two conscious dogs at standardized external conditions, the temperatures of the spinal cord and hypothalamus were altered simultaneously and were correlated with heat production (shivering) and respiratory evaporative heat loss (panting).Combined cooling of spinal cord and hypothalamus at 18, 24, and 30°C air temperature increased heat production by up to 10.2 Kcal/(kg·h). Combined heating of the spinal cord and hypothalamus at the same environmental conditions increased respiratory evaporative heat loss by up to 4.5 Kcal/(kg·h).Compared with the effects of cooling either the spinal cord or the hypothalamus, cooling both together increased the slope of the regression and elevated the threshold temperatures for shivering. With regard to respiratory evaporative heat loss, heating the spinal cord and hypothalamus together mainly lowered the threshold temperatures as compared with warming each area independently.The results suggest that temperature signals, simultaneously generated in spinal cord and hypothalamus, are added to give a combined drive to the effector systems.     

Total body thermosensitivity and its spinal and supraspinal fractions in the conscious goose

1. Effects of general body cooling on heat production: an intravascular heat exchanger was used to alter total body temperature. Heat production increased with decreasing body temperature at an average rate of ?12 W/kg·°C. The rate of rise was independent of air temperature. The threshold body temperature below which heat production rose was lower at higher air temperature.
2. Effects of spinal cord cooling: heat production increased with decreasing spinal temperature at an average rate of ?0.3 W/kg·°C. The rate of rise was not clearly affected by air temperature. The spinal threshold temperature was lower at warm ambient conditions. The results suggest that spinal thermosensitivity in the goose represents only a minor fraction of total body thermosensitivity.
3. Effects of head cooling: heat exchangers enclosing the carotid arteries were used to alter the temperature of the blood supplied to the head. Cooling increased heat production. When the thermosensitivity of the area, which was affected by the heat exchanger, was calculated from the relationship between changes of heat production and brain temperature, values between ?0.74 and ?1.65 W/kg·°C were obtained. Measurements of brain, spinal cord and head skin temperatures suggest that the thermosensitive structures which mediated the responses, were predominantly situated in the brain.

     

Evaluation of hypothalamic thermosensitivity by feedback signals

Summary In four conscious goats with chronically implanted hypothalamic thermodes, forty-three experiments were carried out at environmental conditions between +5°C and 30°C DB/18°C WB. The temperature of the hypothalamus was altered by perfusing the thermodes with water whose temperature, as measured at the inlet of the thermodes, varied between 30°C and 43°C. Heat production, respiratory evaporative heat loss, rectal and oesophageal temperatures were measured. Hypothalamic cooling resulted in an elevation of rectal temperature, while hypothalamic heating caused a fall in temperature. The relation between the intensity of hypothalamic thermal stimulation and the induced change in core temperature can be well described by linear regressions. No difference in sensitivity and no dead band between responses to cold and warm stimulation was found. The experiments show that hypothalamic and extra-hypothalamic sensors of core temperature continuously operate at high sensitivity even within the narrow range of physiologically occurring core temperatures. Qualitatively, this sensitivity is independent of air temperatures between +5°C and +30°C.     

Central thermosensitivity in conscious goats: Hypothalamus and spinal cord versus residual inner body

Experiments were performed on conscious goats to confirm the suggestion that in this species the inner body contains more thermosensitive structures than those residing in the hypothalamus and spinal cord. For this purpose goats were chronically implanted with local thermodes and intravascular heat exchangers to allow independent temperature control of the hypothalamus, spinal cord and residual inner body. With the hypothalamus and spinal cord clamped simultaneously at different levels between 32°C and 40°C, residual internal temperature was lowered by subtracting heat via the intravascular heat exchanger. The residual internal temperature at which shivering and increased heat production occured due to heat extraction, was directly related to the value of the combined hypothalamic and spinal cord clamp temperature. The higher hypothalamic and spinal cord clamp temperatures were, the lower residual internal temperature fell before shivering occurred and heat production rose. Plosts relating residual internal temperature to hypothalamic and spinal cord temperature at different levels of heat production showed the signal input generated within the residual inner body to be of nearly the same order of magnitude as that from the hypothalamus and spinal cord.This work was supported by DFG Je 57/3.     

Influence de stimulations thermiques de la moëlle épinière sur le comportement thermorégulateur du chien

Summary Thermodes were chronically implanted in the epidural space of 3 dogs. The dogs had learned to turn on a fan or infra-red lamps by making a voluntary head movement, in a climatic chamber. Their thermoregulatory behavior was therefore quantitatively measured.Thermal stimulation of the spinal cord was achieved by perfusing water through the spinal thermode.In a warm environment, spinal cord heating produced an increased behavioral fresh air request. On the other hand, spinal cord cooling had no effect upon behavioral fresh air request.In a cold environment, results obtained with one dog showed a decreased behavioral infra-red request during spinal cord heating. Again, thermoregulatory behavior was not changed by spinal cord cooling.These experiments demonstrate the existence of a warm sensitivity in the spinal cord capable of triggering thermoregulatory behavioral response. No evidence was found for a corresponding cold sensitivity.

Travail effectué grâce à l'aide financière du Centre National de la Recherche Scientifique (C.N.R.S.) et de l'institut National de la Santé et de la Recherche Médicale (I.N.S.E.R.M.).     

Effects of total body core cooling on heat production of conscious goats

Experiments were performed to investigate the effect of general body core cooling on heat production at various air temperatures between +1°C and +56°C in conscious goats. An intravascular heat exchanger (IVHE) was used to alter body core temperature independently of air temperature. Heat loss via the IVHE caused a fall in body core temperature, the extent of which depended on the rate of extraction and air temperature. Irrespective of air temperature the decrease in body core temperature resulted in shivering and an increase in heat production, which eventually balanced the heat loss. During steady state conditions the extra heat production was approximately equal to that lost via the IVHE. The threshold body core temperature at which heat production increased in response to central cooling did not significantly alter with air temperature. However, the slopes of the curves describing this response were smaller at higher than at lower air temperatures, which indicated that central thermosensitivity decreased with increasing air temperature. Irrespective of air temperature the threshold temperatures for shivering were higher and the slopes of the curves were steeper than those previously found with combined cooling of the hypothalamus and spinal cord in the same species which indicated the existence of central thermosensors outside the above two mentioned areas.     

Comparison of thermosensitivity in the preoptic/anterior hypothalamic area and the midbrain of the rabbit

Summary To characterize the role of the midbrain temperature-sensitive structure in thermoregulation, the relative importance of thermosensitivity in the hypothalamus and the midbrain was studied in terms of heat production and heat loss in the rabbit. It was found that altering the local temperature in the midbrain had no influence at all on heat loss from the ear surface and also on heat production, while cooling and warming of the preoptic/anterior hypothalamic area induced appropriate thermoregulatory responses.     

Anterior and posterior hypothalamus: Effects of independent temperature displacements on heat production in conscious goats

Summary Three goats were chronically implanted with thermodes to alter the temperatures of the anterior and posterior hypothalamus independently of each other. At an air temperature of +14°C the anterior hypothalamus was cooled with different intensities, while the posterior hypothalamus was simultaneously either warmed (39°C) or cooled (29°C). In both conditions cooling anterior hypothalamus increased heat production. However, the increase was smaller, when the posterior hypothalamus was cooled. The inhibiting effect was most pronounced during the first parts of the periods and diminished with time. Nevertheless, in a separate series of experiments, the effects of posterior hypothalamic cooling were found to persist over periods of 3 h. At an air temperature of +3°C the posterior hypothalamus temperature was altered between 28 and 42°C, while anterior hypothalamus temperature was kept close to its control level. Shivering and heat production decreased with cooling and increased with warming of the posterior hypothalamus. The results suggest that those neurons which reside in the posterior hypothalamus and mediate shivering, are sensitive to temperature. Thermosensitivity of these allegedly integrative neurons affects shivering and heat production in a way inverse to the thermosensitivity of the temperature sensing neurons in the anterior hypothalamus.     

Temperature signals from skin and spinal cord converging on spinothalamic neurons

Summary In anesthetized, artificially ventilated cats with spinal transection at C₂, the temperature of the thoracolumbar spinal cord was varied by means of a water perfused thermode located in the peridural space of the vertebral canal. Single unit activity was recorded from the anterolateral tracts at C₃–C₅. As in a preceding investigation, units were found which were activated either by spinal cord cooling (spinal cold units) or by spinal cord heating (spinal warm units).In addition, the temperature of the skin of the trunk and the hind legs was varied by means of a water perfused coat in order to find out, whether spinal cold and warm units were also influenced by the signals of the cutaneous thermoreceptors. 11 spinal cold units and 10 spinal warm units were investigated in this way. With only one exception, they were found to be influenced by the skin temperature variations.Skin cooling below 38°C led to an increase of activity in 9 investigated spinal cold units. Skin cooling in 8 spinal warm units had, on the average, a negligible effect, although in some units a slight decrease of activity was observed.In several experiments the responses of spinal cold and warm units to skin heating above 40°C were investigated. 4 spinal cold units tested in this way responded to skin heating with an increase of activity. In 9 spinal warm units, activity was either depressed or increased by skin heating; one unit remained unaffected.     

Effects of spinal cord temperature on the generation and transmission of temperature signals in the goat

A series of 38 experiments were performed in five conscious goats at air temperatures of +20° C or +30° C to see whether a temperature dependence of spinal cord signal transmission affects the relationships between body temperature and metabolic rate (MR) or respiratory evaporative heat loss (REHL). Prior to the experiments the animals received peridural thermodes to clamp the spinal cord temperature by perfusion temperatures of 31 °C, 38° C or 43° C (45° C), carotid loops to clamp the brain temperature at 39° C or 39.5° C, and arteriovenous shunts to alter the trunk temperature and to determine thresholds and slopes of MR and REHL over trunk temperature. The trunk temperature thresholds, at which MR and REHL increased, were inversely related to the spinal cord temperature, thereby confirming previous observations on the generation of specific spinal temperature signals. The slopes at which MR rose below the threshold, increased with decreasing spinal cord temperature. The slopes of REHL over trunk temperature were independent of spinal cord temperature. Both observations are at variance with previously observed temperature effects on hypothalamic signal transmission and imply that temperature-dependent signal transmission at the spinal level cannot account for nonlinear interaction of various body temperatures in the control of MR and REHL.     

Effects of skin temperature on cold defense after cutaneous denervation of the trunk

In intact goats the core temperature threshold below which heat production increases with falling core temperature, is inversely related to the temperature of the water bath in which they stand and is therefore assumed to be indicative of the central integration of signals from skin and core temperature receptors. The present study shows that a difference in core temperature thresholds for bath temperatures of 35°C and 40°C persisted after denervation of about two-thirds of the skin of the trunk and limbs. Also, for a given combination of skin and core temperatures, heat production was as great or greater after cutaneous denervation as before. It is concluded that, following denervation of the trunk and upper limbs, intact temperature receptors in the non-denervated skin of the legs and tail, and/or also in tissues between the skin and core, provide important and significant inputs to the temperature regulating system. But these inputs cannot explain fully the thermoregulatory responses observed unless it is assumed that the thermosensitivity of these tissues increased.     

Effects of sodium acetylsalicylate on thermoregulatory responses of rats to different ambient temperatures

The effects of intraperitoneal administration of sodium acetylsalicylate (aspirin) on thermoregulatory responses (T_a) of 15, 22 and 29°C were assessed. Intraperitoneal administration of aspirin produced dose-dependent hypothermia at both 15 and 22°C. The hypothermia was brought about by cutaneous vasodilation (as indicated by an increase of the tail and foot skin temperatures). However, in the heat (29°C), i. p. administration of the same amount of aspirin produced no change in rectal temperature, since the thermoregulatory responses were unaffected by aspirin application at this T_a. Thus it appears that aspirin increases heat loss and leads to hypothermia in rats.     

Effects of thermal stimulation of medulla oblongata and spinal cord on decerebrate rabbits

1. Changes of rectal and ear temperatures, and respiratory and heart rates, during external thermal stress and during thermal displacement of the medulla oblongata and spinal cord have been investigated in rabbits, before and after decerebration, with ether inhalation only during the operation.2. Abrupt exposure of the intact animals to heat (35 degrees C) or cold (5 degrees C) produced appropriate thermoregulatory adjustments such as vasodilatation or vasoconstriction of the ear skin, and increase or decrease of respiratory frequency with little change in rectal temperature. After decerebration, these responses to heat and cold were reduced and rectal temperature was moderately altered.3. In intact animals, heating (42-43 degrees C) and cooling (32-33 degrees C) the medulla and spinal cord also produced appropriate thermoregulatory vasomotor and respiratory responses, although these were smaller than those caused by ambient heating and cooling. Heating these structures also produced bradycardia and cooling tachycardia. In addition, shivering-like movements over extremities and trunks or jaws were elicited, respectively, during spinal or medullary cooling. None of these responses was altered after decerebration.4. These results suggest that while the hypothalamus may be the principal site of thermoregulation, some independent but less powerful thermoregulatory structures exist in the medulla oblongata and spinal cord. Thermal responses to stimulating the latter structures are not results of afferent activation of the hypothalamic mechanism.     

The effects of heating and cooling the spinal cord and hypothalamus on thermoregulatory behaviour in the pig

1. The effects of warming and cooling the spinal cord and hypothalamus on operant thermoregulatory behaviour and posture have been studied in the pig at neutral and cold ambient temperatures.2. Cooling the spinal cord increased and warming decreased the rate of obtaining thermal reinforcement. The response to cooling began with the onset of the stimulus and persisted for up to 5 min followed by a diminution in rate during the remaining 15 min of cooling. The peak of this ;on' response was greater the lower the ambient temperature. The response to heating was a small reduction in rate of reinforcement.3. The ;on' response to cooling the spinal cord was related to changes in temperature of only the cervical region of the cord.4. Cooling the hypothalamus led to an increase in the rate of obtaining heat and this increase was sustained during the 20 min of central cooling. Termination of cooling was followed by a marked depression in rate. Heating the hypothalamus had only a weak inhibitory effect on rate of reinforcement.5. While working for external heat during periods when thermodes over the spine and in the hypothalamus were not being cooled, pigs lay in ;cold defensive' prone positions 25% of the time and lay on their sides 75% of the time. During cooling of the spinal cord the time spent in the prone position was 95% at 5 and 15 degrees C ambients and 71% at a 25 degrees C ambient. During cooling of the hypothalamus the prone posture was adopted 50% of the time.6. When the temperatures of the spinal cord and of the hypothalamus were changed in opposite directions, the operant response was determined by the temperature of the hypothalamus while the postural response was most frequently determined by the temperature of the spinal cord.     

Effects of altering rostral brain stem temperature on temperature regulation in the Adelie penguin,Pygoscelis adeliae

Summary In 4 Adelie penguins, thermodes were implanted in the rostral brain stem. Two animals were additionally equipped with spinal canal thermodes. At thermoneutral (+ 8 to + 16°C) and cold (–18 to –22° C) ambient conditions, the effects of hypothalamic heating and cooling on the surface temperature of one flipper (skin blood flow), oxygen consumption (metabolic heat production) and esophageal (core) temperature were observed in the conscious animals.—Heating the rostral brain stem induced heat defence responses: Heat production was reduced in the cold and skin vasodilatation was evoked at thermoneutral ambient conditions. As a rule, core temperature fell during rostral brain stem heating.—Cooling the rostral brain stem did not induce clear-cut cold defence responses. On the contrary, strong cooling at thermoneutral ambient conditions induced vasodilatation in the skin. In the cold, even slight degrees of rostral brain stem cooling decreased metabolic heat production. As a rule, core temperature fell when the rostral brain stem was cooled.—It is concluded from the results that thermosensitive structures in the stimulated section of the rostral brain stem of the Adelie penguin contribute to the central temperature signal input in the range of normal to elevated core temperatures. These hypothalamic warm signals appear to be at least as effective as spinal warm signals in controlling skin blood flow and metabolic heat production. The inhibition of ongoing thermoregulatory effector activity by rostral brain stem cooling suggests positive temperature coefficients of the integrative and/or efferent neurons in the hypothalamic temperature regulation center of the Adelie penguin.A preliminary report was given at the 45th meeting (autumn meeting) of the Deutsche Physiologische Gesellschaft, Wien, Sept. 23–26, 1975. Pflügers Arch.359, R57 (1975).     

Physical versus pharmacological counter-measures

Summary 128 experiments were carried out on febrile rabbits at air temperatures of 8, 18, 24 and 30° 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 g 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° 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° 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. Antipyretics can be applied at the beginning of effector increase. However, it should be taken into account that in many cases an increased febrile metabolic and circulatory load can be tolerated for the sake of a probable stimulation of the immune system and the elimination of secondary effect of pharmacological therapy.Supported by the Deutsche Forschungsgemeinschaft, SFB 114     

Differentiation of cutaneous and intestinal blood flow during hypothalamic heating and cooling in anesthetized dogs

Summary Blood flow in arteries supplying cutaneous and intestinal vascular regions were simultaneously measured with an electromagnetic flowmeter in anesthetized dogs, paralyzed with succinyl choline. The hypothalamic preoptic region was selectively heated and cooled by means of a stereotaxically inserted, water perfused thermode.Skin blood flow increased during hypothalamic heating and was reduced during hypothalamic cooling. Conversely, intestinal blood flow decreased during heating and increased during cooling. Arterial pressure was not influenced by hypothalamic cooling and decreased slightly during heating.The changes of blood flow distribution observed in the experiments are in keeping with the results obtained during selective spinal cord heating and cooling. It is assumed that antagonistic changes of blood flow in the cutaneous and intestinal vascular beds represent typical thermoregulatory responses of systemic circulation induced by regionally antagonistic changes of vasomotor activity.