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Effects on temperature of monoamines injected into the cerebral ventricles of anaesthetized dogs.

1. In dogs anaesthetized with pentobarbitone sodium an injection of adrenaline or noradrenaline into the cerebral ventricles through a cannula implanted into the left lateral ventricle caused a fall in rectal temperature as a result of cessation of shivering, loss of muscle tone, and skin vasodilatation. 5-Hydroxytryptamine (5-HT) similarly applied caused shivering and a rise in rectal temperature.2. The hypothalamus of the dog thus appears to react to the three monoamines in the same way as in the cat, and not as in the rabbit and sheep.

Animals↗

Monoamine oxidase inhibition: effect on 5-hydroxytryptamine output from perfused third ventricle and body temperature.

1. In cats anaesthetized with pentobarbitone sodium the third ventricle was perfused with artificial c.s.f., the effluent was collected in 30 min samples and assayed for 5-hydroxytryptamine (5-HT) on the rat stomach-strip preparation. Rectal temperature was monitored continuously.2. On perfusion of artificial c.s.f. through the third ventricle, small amounts of 5-HT appeared in the effluent; the amounts decreased with successive samples.3. When tranylcypromine (Parnate), an inhibitor of amine oxidase, was added to the perfusion fluid and perfusion was continued, the 5-HT output increased. This increase was associated with shivering and a rise in temperature which was not, however, maintained.4. When tranylcypromine was injected intraperitoneally, during the fall in temperature produced by the pentobarbitone sodium anaesthesia, the 5-HT output also increased, shivering occurred and the fall in temperature was halted or reversed. The effect on temperature was maintained.5. When the cat was killed and perfusion was continued, the 5-HT output, already elevated by the tranylcypromine before death, increased even further in the next few samples.

Animals↗

Adipose tissue and heat production in the new-born ox (Bos taurus).

1. A histological examination of adipose tissue from 1- and 6-day-old calves showed a structure typical of white adipose tissue and no evidence of brown adipose tissue.2. Infusion of noradrenaline (1.0 mug/kg.min I.V.) into 1-to 6-day-old calves affected heart rate and respiratory rate but did not increase heat production, rectal temperature, skin temperature or skin evaporative loss.3. Cold exposure led to shivering and an increased oxygen consumption in the 6-day-old calf.4. Blood samples taken from 6-day-old calves in the cold (-1 degrees C) appeared to have a higher proportion of unesterified fatty acids in the total blood lipid than samples taken in an environment of 20 degrees C, but no change in fatty acid composition was found.5. It has been concluded that there is no non-shivering thermogenesis in the young calf.

Adipose Tissue↗

The hypothermic effect of tetrodotoxin in the unanaesthetized cat.

1. The hypothermic effect on unanaesthetized cats of tetrodotoxin injected I.V. or into the lateral cerebral ventricle was examined.2. At an ambient temperature (T(a)) of 22 degrees C, tetrodotoxin given intraventricularly was over 400 times more potent in lowering body temperature (T(b)) than when given I.V. The magnitude of the hypothermia was dose-dependent for both routes. Decreases in T(b) as great as 6.8 degrees C were induced by infusions or multiple injections of tetrodotoxin into the ventricle.3. Tetrodotoxin also lowered T(b) at T(a) = 13, 30 or 35 degrees C. Tachypnoea, which lasted for longer durations and which became more intense the higher the T(a), accompanied development of hypothermia. Shivering was observed only during recovery from hypothermia at 13 degrees C.4. During the tetrodotoxin-induced hypothermia, animals were still able to regulate against environmental thermal stresses.5. EDTA disodium salt, leucocytic pyrogen and prostaglandin E(1) antagonized the hypothermic effect of tetrodotoxin when they were administered during recovery from tetrodotoxin.6. Activation of heat-loss mechanisms, and the absence of compensatory shivering during development of hypothermia after tetrodotoxin administration, plus lowering of T(b) by tetrodotoxin at T(a) above as well as below the thermoneutral temperature, indicate that lowering of the thermoregulatory set-point is the mechanism by which centrally or peripherally administered tetrodotoxin lowers T(b). Further evidence for set-point lowering after intraventricular administration of tetrodotoxin is provided by persistence of the ability to regulate against both heat and cold stresses during hypothermia. The possibility that the decrease in set-point could be due to the well known action of tetrodotoxin to block transient increases in membrane sodium ion conductance is discussed in terms of a recent hypothesis regarding ionic control of the thermoregulatory set-point.

Animals↗

Reflex activation of rat fusimotor neurons by body surface cooling, and its dependence on the medullary raphe.

The nature of muscle efferent fibre activation during whole body cooling was investigated in urethane-anaesthetized rats. Multiunit efferent activity to the gastrocnemius muscle was detected when the trunk skin was cooled by a water-perfused jacket to below 36.0 +/- 0.7 degrees C. That efferent activity was not blocked by hexamethonium (50 mg kg(-1), i.v.) and was not associated with movement or electromyographic activity. Cold-induced efferent activity enhanced the discharge of afferent filaments from the isotonically stretched gastrocnemius muscle, demonstrating that it was fusimotor. Fusimotor neurons were activated by falls in trunk skin temperature, but that activity ceased when the skin was rewarmed, regardless of how low core temperature had fallen. While low core temperature alone was ineffective, a high core temperature could inhibit the fusimotor response to skin cooling. Fusimotor activation by skin cooling was often accompanied by desynchronization of the frontal electroencephalogram (EEG), but was not a simple consequence of cortical arousal, in that warming the scrotum desynchronized the EEG without activating fusimotor fibres. Inhibition of neurons in the rostral medullary raphé by microinjections of glycine (0.5 m, 120-180 nl) reduced the fusimotor response to skin cooling by 95 +/- 3%, but did not prevent the EEG response. These results are interpreted as showing a novel thermoregulatory reflex that is triggered by cold exposure. It may underlie the increased muscle tone that precedes overt shivering, and could also serve to amplify shivering. Like several other cold-defence responses, this reflex depends upon neurons in the rostral medullary raphé.

Action Potentials↗

Improved cold tolerance and its mechanism in cold-acclimated rats by high fat diet feeding.

Cold tolerance and metabolic responses to cold were studied in cold-acclimated rats on high fat diet (CAHF). Cold tolerance at-5 degrees C was assessed by fall of colonic temperature of clipped rats after 18 h of fasting. Rate of fall in colonic temperature was greatest in warm-acclimated control rats (WAST), slowest in cold-acclimated rats on standard diet (CAST), and remained unchanged in CAHF during cold exposure for 240 min. Increment in blood free fatty acid (FFA) concentration 80 min after cold exposure was greatest in WAST, less in CAST, and least in CAHF. Blood glucose decreased similarly in WAST and CAST after cold exposure, while it remained unchanged in CAHF. Blood beta-hydroxybutyrate also increased similarly in WAST and CAST, while it did not change in CAHF. Nonshivering thermogenesis tested by noradrenaline was greatest in CAHF, followed by CAST and WAST. Shivering induced by cold exposure was less pronounced in CAST than in WAST and did not develop in CAHF; changes in colonic temperature were inversely related to the extent of shivering during cold exposure for 90 min. These results suggest that an integrating effect of cold and high fat diet could improve cold tolerance much more than cold acclimation itself, possibly through enhanced nonshivering thermogenesis caused by metabolic modifications such as increased lipid use and gluconeogenesis.

Acclimatization↗

Influence of cold and warm acclimation on neuronal responses in the lower brain stem.

Neurons in two lower brain stem areas, the nucleus raphe magnus and the subcoeruleus region, have been shown to be part of the thermoafferent system. It is concluded from microcut experiments in unanaesthetized guinea pigs that inhibition of shivering caused by nucleus raphe magnus stimulation is mediated partly by ascending and partly by descending efferents of the nucleus raphe magnus. Electrical stimulation of the subcoeruleus area caused excitatory metabolic responses. Interruption of the ascending efferents of the subcoeruleus area did not prevent the metabolic activation. It is concluded that the excitatory responses are partly mediated by descending efferents of the subcoeruleus area. The descending pathways project mainly to motoneurone pools and to dorsal horn cells. In cold-acclimated guinea pigs, the average maximum activity of bell-shaped subcoeruleus cold-responsive units was reduced significantly in comparison with cold-responsive neurons in animals acclimated to normal room temperature. Furthermore, peak activity of warm-responsive units in the nucleus raphe magnus was larger in cold-acclimated animals than in animals acclimated to normal room temperature. These neuronal changes may contribute via descending lower loops and via ascending upper loops to long-term slope reduction of metabolic cold defence and shivering threshold displacements.

Acclimatization↗

Free fatty acid oxidation in bovine muscle in vivo: effects of cold exposure and feeding.

A mixture of (1-14C)-labeled free fatty acids (FFA), complexed in bovine plasma, was infused into the abdominal aorta of conscious young steers exposed to thermoneutral or moderately cold conditions for several hours and fed 6 or 22 h before the experiment. The uptake, release, and oxidation of FFA in one hindlimb was calculated from simultaneous measurements of leg blood flow and arteriovenous difference in the specific activities of plasma 14C-FFA and blood 14CO2. Despite an invariable net release of FFA from the resting leg, uptake of 14C-FFA was considerable; of this only 14 and 3% was immediately converted to 14CO2 in fasted and fed steers, respectively. During cold exposure, increases in whole-body oxygen consumption (VO2), arterial concentration and turnover rate of plasma FFA, and a decrease in respiratory quotient were accompanied by much greater increases in VO2, uptake, and oxidation of FFA by the shivering leg. Even so, most FFA taken up were apparently not immediately oxidized to CO2, and possible alternatives for FFA metabolism in shivering muscle are discussed.

Animals↗

Thermoregulatory heat production in cold-reared and warm-reared pigs.

Pigs were reared from 2 wk of age in either 10 or 35 degrees C and fed ad libitum. At 8 wk of age they were tested for the presence of regulatory nonshivering thermogenesis by administration of norepinephrine (NE) and propranolol. In addition, an electromyogram and carotid temperature, as well as a heat flow and skin temperature from one site, were monitored while the pigs were at ambient temperatures of 10, 15, 20, 25, and 30 degrees C. Cold-reared pigs showed a heightened response to NE in cold compared to thermally neutral environments. This was not observed in warm-reared pigs. Propranolol depressed O2 consumption more in cold-reared than in warm-reared pigs. Pigs reared in the cold also showed a higher intensity of shivering, tissue conductance, and skin temperature than warm-reared littermates. The shivering response of cold-reared pigs was more sensitive to changes in skin temperature than in warm-reared pigs.

Acclimatization↗

Circadian and arousal state influences on thermoregulation in the pigeon.

We report here the characteristics of spinal thermosensitivity in pigeons as a function of arousal state and time of day. At any time in the light-dark (LD) cycle, the thresholds for shivering and panting were lower during non-rapid-eye-movement (NREM) sleep than during wakefulness. These thresholds in both awake and sleeping animals were lower during D than during L. The gain of the metabolic response to spinal cooling was nearly the same in wakefulness and NREM sleep. Shivering and panting responses to spinal thermal stimulations were impaired during REM sleep compared with wakefulness and NREM sleep. The results support the idea that central nervous system mechanisms controlling arousal states and circadian rhythmicity have separate and additive influences on temperature regulation in the pigeon.

Animals↗

Potentiated muscular thermogenesis in cold-acclimated muscovy duckling.

The capacity for nonshivering thermogenesis (NST) was examined in 26- to 27-day cold-acclimated (CA) muscovy ducklings reared for 21 days at 4 degrees C. Metabolic rate and integrated electromyographic (EMG) muscle activity were measured at ambient temperature ranging from -10 to 28 degrees C. Compared with controls reared at 30 degrees C, CA ducklings were more resistant to cold and had higher peak metabolic rate in extreme cold. Shivering threshold temperature of CA ducklings was 14.2 degrees C lower than lower critical temperature, whereas for controls the two temperatures were similar. Thus CA ducklings exhibited an NST in moderate cold. In addition, at temperatures that produced shivering, EMG activity in CA duckling muscle was lesser than that of controls, even at a higher metabolic rate. Because these ducklings are devoid of brown adipose tissue, these results indicated an increased thermogenic efficiency of muscular activity in CA ducklings.

Acclimatization↗

Skeletal muscle as the major site of nonshivering thermogenesis in cold-acclimated ducklings.

Despite their lack of brown adipose tissue, 6-wk-old cold-acclimated muscovy ducklings (4 degrees C; CA) exhibit nonshivering thermogenesis (NST) in the cold. To determine the site of this NST, the regional distribution of blood flow was measured by the microsphere method in the thermoneutral zone (25 degrees C) and during acute exposure to cold (8 degrees C). Ducklings reared at thermal neutrality (TN), which use shivering to produce extra heat in the cold, were compared with CA ducklings, which substitute NST for shivering. Further, the contribution of skeletal muscle thermogenesis to the increased heat production in the cold was estimated by measuring leg muscle blood flow and arteriovenous difference in oxygen content [(a-v)O2] across the leg, enabling an estimation of muscle O2 consumption. During cold exposure, a similar increase in total leg muscle blood flow occurred in TN and CA ducklings (+127 and +130% respectively), while hepatic arterial blood flow increased less (+56 to +37%, respectively). This rise in blood flow was accounted for by an increase in cardiac output, which was smaller in CA than in TN ducklings, and in both groups by a redistribution of blood flow to the most thermogenic organs (skeletal muscles and liver). The (a-v)O2 across the leg was not changed by cold exposure, indicating that the increase in leg muscle O2 consumption resulted mainly from the increase in blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

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.

Animals↗

Core temperature "null zone".

An experimental protocol was designed to investigate whether human core temperature is regulated at a "set point" or whether there is a neutral zone between the core thresholds for shivering thermogenesis and sweating. Nine male subjects exercised on an underwater cycle ergometer at a work rate equivalent to 50% of their maximum work rate. Throughout an initial 2-min rest period, the 20-min exercise protocol, and the 100-min recovery period, subjects remained immersed to the chin in water maintained at 28 degrees C. On completion of the exercise, the rate of forehead sweating (Esw) decayed from a mean peak value of 7.7 +/- 4.2 (SD) to 0.6 +/- 0.3 g.m-2.min-1, which corresponds to the rate of passive transpiration, at core temperatures of 37.42 +/- 0.29 and 37.39 +/- 0.48 degrees C, as measured in the esophagus (Tes) and rectum (Tre), respectively. Oxygen uptake (VO2) decreased rapidly from an exercising level of 2.11 +/- 0.25 to 0.46 +/- 0.09 l/min within 4 min of the recovery period. Thereafter, VO2 remained stable for approximately 20 min, eventually increased with progressive cooling of the core region, and was elevated above the median resting values determined between 15 and 20 min at Tes = 36.84 +/- 0.38 degrees C and Tre = 36.80 +/- 0.39 degrees C. These results indicate that the core temperatures at which sweating ceases and shivering commences are significantly different (P less than 0.001) regardless of whether core temperature is measured within the esophagus or rectum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ventilatory and metabolic responses to cold and hypoxia in intact and carotid body-denervated rats.

The effects of hypoxia on thermoregulation and ventilatory control were studied in conscious rats before and after carotid denervation (CD). Measurements of metabolic rate (VO2), ventilation (V), shivering intensity (SI), and colonic temperature (Tc) were made in groups of eight rats subjected to three protocols. In protocols 1 and 2, at ambient temperature (Ta) of 25 and 5 degrees C, respectively, rats were exposed to normoxia and hypoxia [inspired O2 fraction (FIO2) 0.13-0.11]. In protocol 3, Ta was decreased from 25 to 5 degrees C in 30-min steps of 5 degrees C. Recordings were made in normoxia and hypoxia (FIO2 0.12). The results show that in both intact and CD rats 1) in normoxia, cold exposure increased VO2, V, and SI, and these increases were proportional to the decrease in Ta; 2) hypoxia induced only a transient decrease in SI, and, for a given Ta, VO2 was reduced whereas V and SI were increased; and 3) in CD rats, V increased less during cold exposure in both normoxia and hypoxia; VO2 and Tc were more depressed during hypoxia. It is concluded that 1) the interaction between Ta and FIO2 in the control of V is partly dependent on the carotid body afferents, 2) shivering thermogenesis may be transiently affected by hypoxia independently of the carotid body afferents, and 3) nonshivering thermogenesis may be directly inhibited by hypoxia, especially during cold exposure.

Afferent Pathways↗

Treatment of mild immersion hypothermia by direct body-to-body contact.

Body-to-body contact is often recommended for rewarming mildly hypothermic victims in the field. This procedure involves a euthermic individual donating heat to the recipient by direct contact in an insulated bag. However, this technique has not been critically evaluated and may not be beneficial because there is limited direct contact between recipient and donor, peripheral vasoconstriction may impair heat transfer to the core, skin warming may blunt the recipient's shivering response, and cold stress to the donor may be excessive. The present study was designed to evaluate whether donation of heat by a donor would be sufficient to enhance rewarming of a hypothermic subject (recipient). Six pairs of recipients (5 men, 1 woman) and donors (2 men, 4 women) participated in the study. Esophageal and skin temperatures, cutaneous heat flux, and oxygen consumption were measured. Recipients were immersed in 8 degrees C water until esophageal temperature decreased to a mean of 34.6 +/- 0.7 degrees C (SD). They then were rewarmed by one of three methods: rewarming by the endogenous heat generated by shivering only (SH), body-to-body rewarming (BB), or rewarming with a constant-heat source manikin (MAN). Mean afterdrop for the three conditions was 0.54 +/- 0.2, 0.54 +/- 0.2, and 0.57 +/- 0.2 degrees C for SH, BB, and MAN, respectively (NS), and the rate of rewarming was 2.40 +/- 0.8, 2.46 +/- 1.1 and 2.55 +/- 0.9 degrees C/h for SH, BB, and MAN, respectively (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of hypoxia on metabolic rate in awake ponies.

To determine the effect of hypoxia on metabolic rate (VO2) of ponies, on 2 days we studied ponies that were breathing room air for 1 h followed by 5 h of either hypoxic hypoxia (fractional concn of inspired O2 = 0.126) or 5 h of CO hypoxia. Control arterial PO2 was 103 +/- 1.2 Torr, and at 5 min and 5 h of hypoxic hypoxia, arterial PO2 was 53.1 +/- 1.8 and 41.0 +/- 1.8 Torr, respectively. There was a time-dependent hypocapnia and alkalosis during hypoxic hypoxia. During CO hypoxia, carboxyhemoglobin increased to 25% after 30 min and remained constant thereafter. With increased carboxyhemoglobin, arterial PCO2 was 1.3 Torr above (P < 0.05) and 1.5 Torr (P < 0.05) below control levels after 30 min and 3 h, respectively. There were no significant (P > 0.10) changes in VO2 during either hypoxic or CO hypoxia. However, in 50% of the ponies, VO2, pulmonary ventilation, and rectal temperature increased and shivering was evident after 30 min of hypoxia. Peak values of pulmonary ventilation, VO2, and shivering occurred at approximately 2 h with a subsequent return toward control levels. We conclude that, in contrast to smaller mammals, acute hypoxia does not depress VO2 of ponies. The hypermetabolism and hyperthermia during chronic hypoxia in some ponies may reflect a transient failure in thermoregulation.

Animals↗

Human thermoregulatory responses during serial cold-water immersions.

This study examined whether serial cold-water immersions over a 10-h period would lead to fatigue of shivering and vasoconstriction. Eight men were immersed (2 h) in 20 degrees C water three times (0700, 1100, and 1500) in 1 day (Repeat). This trial was compared with single immersions (Control) conducted at the same times of day. Before Repeat exposures at 1100 and 1500, rewarming was employed to standardize initial rectal temperature. The following observations were made in the Repeat relative to the Control trial: 1) rectal temperature was lower and heat debt was higher (P < 0.05) at 1100; 2) metabolic heat production was lower (P < 0.05) at 1100 and 1500; 3) subjects perceived the Repeat trial as warmer at 1100. These data suggest that repeated cold exposures may impair the ability to maintain normal body temperature because of a blunting of metabolic heat production, perhaps reflecting a fatigue mechanism. An alternative explanation is that shivering habituation develops rapidly during serially repeated cold exposures.

Adult↗