Central Temperature Regulation Research Articles

Prevention and management of inadvertent perioparatve hypothermia

Центральная температура тела человека служит важнейшим показателем, мониторируемым в клинической практике анестезиологии и интенсивной терапии. Современные анестетики влияют на процессы регуляции центральной температуры и приводят к её снижению в периоперационном периоде. Непреднамеренная интраоперационная гипотермия сопровождает многие операции, проводимые под общей и регионарной анестезией. Она значительно увеличивает риск кардиальных и инфекционных послеоперационных осложнений, на её фоне возрастают послеоперационная кровопотеря и потребность в гемотрансфузии. Пациенты в условиях гипотермии медленнее просыпаются, их пробуждение чаще сопровождается мышечной дрожью. Периоперационная гипотермия приводит к увеличению сроков госпитализации и внутрибольничной летальности. В связи с этим предотвращение непреднамеренной периоперационной гипотермии - важная часть анестезиологического обеспечения больного во всех областях хирургии. Поддержание нормотермии во время операции служит важной составляющей всех программ ранней послеоперационной активизации больных.

Thermosensory perception regulates speed of movement in response to temperature changes in Drosophila melanogaster.

Temperature influences the physiology and behavior of all organisms. For ectotherms, which lack central temperature regulation, temperature adaptation requires sheltering from or moving to a heat source. As temperature constrains the rate of metabolic reactions, it can directly affect ectotherm physiology and thus behavioral performance. This direct effect is particularly relevant for insects, as their small bodies readily equilibrate with ambient temperature. In fact, models of enzyme kinetics applied to insect behavior predict performance at different temperatures suggesting that thermal physiology governs behavior. However, insects also possess thermosensory neurons critical for locating preferred temperatures, showing cognitive control. This suggests that temperature-related behavior can emerge directly from a physiological effect, indirectly as a consequence of thermosensory processing, or through a combination of both. To separate the roles of thermal physiology and cognitive control, we developed an arena that allows fast temperature changes in time and space, and in which animals' movements are automatically quantified. We exposed wild-type Drosophila melanogaster and thermosensory receptor mutants to a dynamic temperature environment and tracked their movements. The locomotor speed of wild-type flies closely matched models of enzyme kinetics, but the behavior of thermosensory mutants did not. Mutations in thermosensory receptor gene dTrpA1 (Transient Receptor Potential A1) expressed in the brain resulted in a complete lack of response to temperature changes, while mutations in peripheral thermosensory receptor gene Gr28b(D) resulted in a diminished response. We conclude that flies react to temperature through cognitive control, informed by interactions between various thermosensory neurons, the behavioral output of which resembles models of enzyme kinetics.

Chocs d’allure septique

Widely used for classification of patients in clinical studies, the usual definition of septic shock is however regularly criticized for its lack of specificity. Many diseases are likely to produce clinical or biological manifestations similar to those observed in septic shock. These “septiclike shocks” may be related to different causes like acute systemic inflammation, global ischemia-reperfusion, toxic reaction, anaphylactic troubles, disorders in central regulation of temperature as well as metabolic or endocrine disturbances. It is of crucial importance to suspect these etiologies, since treatment is often totally different, requiring the immediate implementation of specific therapies.

Malignant hyperthermia: a pharmacogenetic disease of Ca++ regulating proteins.

Malignant hyperthermia (MH) is a pharmacogenetic, life-threatening hypermetabolic syndrome in genetically predisposed individuals exposed to certain anesthetic agents. Discovered by Denborough and Lovell [1] in 1960, MH was associated with high mortality and morbidity as the cause was unknown and an effective treatment was unavailable. There is no classic clinical presentation of the syndrome, and the onset and signs of MH are dependent upon known and unknown environmental and genetic factors. Initial theories involved central temperature regulation defects or uncoupling of oxidative phosphorylation in mitochondria [2], but later investigations targeted skeletal muscle as the affected organ. Subsequently freshly biopsied skeletal muscle was used for in vitro pharmacologic contracture testing to discriminate between normal and MH-affected muscle and remains the "gold standard" for MH diagnosis. Spontaneous, genetic models for MH were discovered in pigs and dogs and substantial knowledge about MH was gained from these valuable resources. The abnormal contracture response of MH skeletal muscle evoked a focus on calcium regulation, and abnormalities in calcium release (as opposed to calcium sequestration) mechanisms were discovered. About this same time the major calcium release channel in the skeletal muscle sarcoplasmic reticulum membrane was purified and named the ryanodine receptor [3]. Although the ryanodine receptor represents one of the largest functional proteins, the enormous gene encoding the 5021 amino acids comprising the ryanodine receptor subunit was eventually cloned [4,5]. Patient and dedicated work on the ryanodine receptor gene has found linkage to MH in the pig [6], dog [7], and among several different mutations and MH in unrelated human families [8,9]. Expression of these mutations in HEK cells has resulted in abnormal calcium release [10,11], supporting but not proving a causal basis for MH. In this review each of the areas mentioned above is discussed in detail revealing a wonderful success story that changed the anesthesiologist's "worst nightmare" from a syndrome with high mortality and morbidity to a reasonably well managed disease today. This success story includes unraveling the molecular basis for the disease and brings its pathoetiologic and diagnostic aspects toward molecular genetic resolution.

Clonidine Therapy for Shapiro's Syndrome

Shapiro's syndrome comprises agenesis of the corpus callosum in association with episodic hyperhidrosis and hypothermia. We describe a 25-year-old man who is the twentieth case to be reported. There was no evidence of epilepsy, sympathetic nervous system dysfunction or inappropriate vasopressin release. However, investigation demonstrated a central defect in temperature regulation with an abnormally low hypothalamic set-point and normal homeothermic reflexes. Therapy with clonidine, an alpha 2-adrenoceptor agonist, was associated with remission of symptoms: these recurred on four occasions when clonidine was withdrawn. Clonidine therapy was also associated with a return to normal central temperature regulation. We suggest that the efficacy of clonidine reflects an action on hypothalamic thermoregulation rather than on peripheral catecholamine release. These findings have implications for the use of clonidine in other patients with Shapiro's syndrome and in more common disorders of temperature control, including perimenopausal flushing.

Endorphin-induced hyperthermia: characterization of the exogenously and endogenously induced effects.

Endorphins-like opiates-were found to increase temperature at very low doses and to decrease temperature at high doses. Not only the decreasing, but also the increasing effect on temperature, seems to be mediated through opiate receptors, since it proved to be antagonizable by naloxone and to be diminished in morphine-tolerant and-dependent animals. Like opiate-induced hyperthermia, both the pharmacological as well as the supposedly physiological increase in temperature induced by endorphins were strongly diminished in restrained animals. Hyperthermia induced by pyrogens, however, was not antagonizable by either naloxone or restraining of the animals. Maintenance of normal body temperature in animals being exposed to acute cold could not be disturbed by administration of naloxone. As a whole, such findings support the suggestion derived from our previous observation that physiologically induced naloxone-antagonizable hyperthermia may be a sensitive measure for endorphin release. However, endorphins although being potent hyperthermic modulators of temperature, do not seem to be directly involved in the central regulation of temperature. Instead, the physiologically induced increase in temperature by endorphins seems to represent some epiphenomenon of physiological events primarily initiated for physiological requirements other than the support of thermostability.

Central regulation of temperature in cold environments. II. A dynamic model with three temperature inputs

A model for the regulation of temperature in cold-stressed animals has been developed using CSMP (a real time program). The model, which centers on the integration of signals by the central nervous system, includes: (a) sensory pathways to the neurocontroller from spinal cord, cutaneous and hypothalamic thermoreceptors; and (b) provision for sorting, comparison and multiplication of inputs. In the model, signals from the central nervous system control effectors for both shivering and nonshivering heat production. An output, hypothalamic temperature, calculated as a function of time, is in a form allowing comparison with experimental data. The effect of fever has been simulated by varying the sensitivities of the hypothalamic and spinal cord receptors, or their set points. Critical experiments have been outlined to test the applicability of this model, as compared with models having only two sensory pathways to a neurocontroller.

Central regulation of temperature in cold environments: I. A dynamic model with two temperature inputs

A preoptic-hypothalamic network representing neural regulation of temperature in cold-stressed animals has been modeled using CSMP (a program for real time processes). The calculated outputs of this model can be readily compared with experimental data, and the neural regulator can be integrated with other homeostatic regulators. The calculated outputs consist of signals for activating shivering and nonshivering heat production as two inputs, hypothalamic and cutaneous temperature, are varied in time. To simulate the effect of a pyrogen-induced fever, a parameter in the model is varied to alter the temperature sensitivity of one class of hypothalamic neurons. Finally, calculations are included to allow a critical comparison of this model with other thermoregulatory models for cold-stressed animals.

Central regulation of temperature in hibernation and normothermia

Normothermic hibernators respond proportionally to both peripheral and brain temperature changes like other mammals. Their quantitative responsiveness to peripheral and brain temperature inputs are consistent with body-size relationships seen in other vertebrates. The basic temperature regulatory mechanisms seen in seasonal hibernators are not altered with season although certain response parameters, such as vasomotion, are not obvious in prehibernating marmots. During hibernation, hibernators respond to peripheral- and core-temperature manipulation in a manner which is consistent with the contention that temperature is regulated in a similar but less precise manner to that seen during normothermia.

Thermoregulatory effects of intraventricular injection of noradrenaline in the mouse and the influence of ambient temperature.

1. At an ambient temperature of 20 degrees C, intraventricular injection of noradrenaline in the mouse resulted in hypothermia accompanied by a fall in metabolic rate and by cutaneous vasodilatation. Subcutaneous injection of noradrenaline resulted in hyperthermia with raised metabolic rate and cutaneous vasodilatation.2. The hypothermia and fall in oxygen consumption rate following intraventricular noradrenaline were prevented by pre-treatment with subcutaneous propranolol, while the cutaneous vasodilatation was un-affected. However, the effects of subcutaneously injected noradrenaline were completely abolished by subcutaneous propranolol. Intraventricular propranolol did not modify the hypothermic effect of intraventricular noradrenaline.3. The direction of the effect on body temperature of intraventricular noradrenaline was dependent upon ambient temperature; hypothermia occurring at low (15 degrees C) and hyperthermia at high (36 degrees C) ambient temperatures. However, when the possibility of any peripheral action of noradrenaline escaping into the systemic circulation was prevented by prior subcutaneous injection of propranolol, significant hypothermia could be detected at temperatures as high as 32 degrees C.4. The possibility that the effects of intraventricular noradrenaline could be due to complete abolition of central temperature regulation was further excluded by the occurrence of thermal salivation in all animals during experiments performed at 36 degrees C.5. It is suggested that, in the mouse, the hypothermic actions of intraventricular noradrenaline are due to a central effect, while its hyperthermic effects at high ambient temperature are due to escape of noradrenaline into the peripheral circulation. The hypothermia could be the result of selective activation of central heat loss mechanisms.6. Intraventricular noradrenaline was without effect on brain plasma-space although exposure to 100% oxygen caused a detectable fall.

The effect of intraventricular injections of noradrenaline, 5-hydroxytryptamine, acetylcholine and tranylcypromine on the ox (Bos taurus) at different environmental temperatures.

1. Noradrenaline, 5-hydroxytryptamine (5-HT), acetylcholine and tranylcypromine were injected or infused into the lateral ventricle of the ox. The effects of these drugs on heart and respiration rates, heat production, rectal, skin and hypothalamic temperatures and skin evaporative loss were measured when the animal was exposed to environmental temperatures ranging from -1 degrees C to +30 degrees C.2. Acetylcholine (0.001-2 mg) had no detectable effect on temperature regulation at 20 degrees C.3. In small doses (0.005-0.05 mg) 5-HT had no detectable effect. Larger doses (2-5 mg) given in a cold environment (-1 degrees C) also had no effect but the same doses given in warm environments (15-30 degrees C) caused increases in skin temperatures, skin evaporative loss and respiratory rate, and decreases in rectal and hypothalamic temperatures.4. Infusion of tranylcypromine (0.107 ml./min of a 1 in 50 solution) in a warm environment (20 degrees C) also caused a decrease in rectal temperature after a delay of 1-1(1/2) hr during which no effects were apparent.5. Noradrenaline (2 mg) had no effect on temperature regulation when injected into animals in a warm environment (30 degrees C). When injected (1 mg) into animals in a cold environment (-1 degrees C) shivering stopped and heat production and rectal and hypothalamic temperatures were decreased.6. It is concluded that intraventricular 5-HT and noradrenaline both cause a decrease in body temperature, and it is unlikely that central temperature regulation in the ox is mediated only by these two substances.

Central temperature regulation in the conscious rabbit after monoamine oxidase inhibition.

1. Measured thermal loads were applied to conscious rabbits by intravenous infusions of hot or cold saline. The responses of the central temperature regulating mechanism were assessed by measuring hypothalamic temperature change. The relationship between thermal load and temperature response was established in normal animals.2. Intramuscular injection of tranylcypromine (20 mg/kg. day for 6-8 days) had no effect upon resting temperature or the temperature response to thermal loads, though the diencephalic concentrations of noradrenaline and 5-hydroxytryptamine (5-HT) were increased.3. Either hypothalamic monoamines are not concerned in the regulation of normal temperature or there is a monoamine ;pool' in the hypothalamus which is concerned with temperature regulation but which is unaffected by monoamine oxidase inhibition.

Central temperature regulation in the spinal man.

Central temperature regulation in the spinal man.

TEMPERATURE IN THE EXTERNAL AUDITORY MEATUS AS AN INDEX OF CENTRAL TEMPERATURE CHANGES.

The temperature of the wall of the external auditory meatus has been investigated. Changes in ear temperature reflect changes of sublingual temperature quite accurately and are well correlated with cutaneous vasomotor responses induced by body heating. The temperature of the external auditory meatus is little affected by reflex vasomotor changes. It is easily measured without discomfort or danger and provides a valid indication of temperature changes at the central receptors. There is a considerable temperature gradient down the wall of the meatus so that absolute temperature levels are probably not of value. ear temperature in man; central temperature regulation in man Submitted on February 24, 1964

Influence of the corpus striatum upon electrical potentials of the liver

The effect of stimulation of the caudate nucleus, hypothalamus, midbrain tegmentum, splanchnic nerve, or vagus nerve upon the liver was studied in cats using d-c potentials of the liver surface (LP) as an indicator. Stimulation of these areas or of the splanchnic nerve induced a gradual increase of the positive LP. The maximum (1–2 mv) was reached about 30 sec after the beginning of the reaction. The gradually declining curve returned to or close to the resting value about 30 to 60 sec later. Vagal stimulation usually produced a fluctuation of LP to the negative side. In control experiments, stimulation of the pole and basal parts of the frontal lobe, of the sigmoid gyri and of the dura did not significantly change LP. The effect of caudate stimulation upon the liver did not depend on the corticofugal fibers originating in the sigmoid gyri and frontal lobe, in contrast to the effect upon smooth muscles. The effect of stimulation of the caudate nucleus persisted after extensive homolateral lesions of the pallidum or of the amygdala, but it was no longer demonstrable after extensive combined lesions of these ganglia. It was distinctly decreased by large hypothalamic lesions on the side of the caudate stimulation and practically abolished by extensive bilateral lesions in the caudal hypothalamus. Transection of the spinal cord above the origin of the splanchnic nerves prevented or abolished the effect of stimulation of the caudate nucleus or the hypothalamus upon LP, whereas this reaction persisted after bilateral vagotomy. In aggreement with the assumption that the influence of the caudate nucleus and of the hypothalamus upon the liver is part of the central temperature regulation, it was found that the rise in LP was accompanied by an elevation of the liver temperature.