Effect of rapid and slow cooling on thermoregulatory responses in hypertensive and normotensive rats after calcium administration

The effect of iontophoretic administration of calcium ions to skin in the area of cold stimulus application on the thermal thresholds and the magnitude of cold defense responses in normotensive Wistar and hypertensive ISIAH rats was studied. In thermoneutral conditions, administration of calciumions wos without effect on the measured thermoregulatory parameters. Under the effect of calcium, the thresholds of all the thermoregulatory responses to cooling (such as heat loss, oxygen consumption, shivering) are lowered and the values of heat loss and shivering thermogenesis are considerably increased. The effects of calcium on thermoregulatory responses depend on the rate of cooling. All changes are more expressive in hypertensive rats. The increased sensitivity of hypertensives to calcium suggests that change in their calcium metabolism may be a cause of the observed shifts in the thermoregulatory response to cold.     

Exertion-induced fatigue and thermoregulation in the cold

Cold exposure facilitates body heat loss which can reduce body temperature, unless mitigated by enhanced heat conservation or increased heat production. When behavioral strategies inadequately defend body temperature, vasomotor and thermogenic responses are elicited, both of which are modulated if not mediated by sympathetic nervous activation. Both exercise and shivering increase metabolic heat production which helps offset body heat losses in the cold. However, exercise also increases peripheral blood flow, in turn facilitating heat loss, an effect that can persist for some time after exercise ceases. Whether exercise alleviates or exacerbates heat debt during cold exposure depends on the heat transfer coefficient of the environment, mode of activity and exercise intensity. Prolonged exhaustive exercise leading to energy substrate depletion could compromise maintenance of thermal balance in the cold simply by precluding continuation of further exercise and the associated thermogenesis. Hypoglycemia impairs shivering, but this appears to be centrally mediated, rather than a limitation to peripheral energy metabolism. Research is equivocal regarding the importance of muscle glycogen depletion in explaining shivering impairments. Recent research suggests that when acute exercise leads to fatigue without depleting energy stores, vasoconstrictor responses to cold are impaired, thus body heat conservation becomes degraded. Fatigue that was induced by chronic overexertion sustained over many weeks, appeared to delay the onset of shivering until body temperature fell lower than when subjects were rested, as well as impair vasoconstrictor responses. When heavy physical activity is coupled with underfeeding for prolonged periods, the resulting negative energy balance leads to loss of body mass, and the corresponding reduction in tissue insulation, in turn, compromises thermal balance by facilitating conductive transfer of body heat from core to shell. The possibility that impairments in thermoregulatory responses to cold associated with exertional fatigue are mediated by blunted sympathetic nervous responsiveness to cold is suggested by some experimental observations and merits further study.     

The effect of dynamic exercise on resting cold thermoregulatory responses measured during water immersion

The purpose of this study was to evaluate the effect of exercise on the subsequent post-exercise thresholds for vasoconstriction and shivering measured during water immersion. On 2 separate days, seven subjects (six males and one female) were immersed in water (37.5 degrees C) that was subsequently cooled at a constant rate of approximately 6.5 degrees C x h(-1) until the thresholds for vasoconstriction and shivering were clearly established. Water temperature was then increased to 37.5 degrees C. Subjects remained immersed for approximately 20 min, after which they exited the water, were towel-dried and sat in room air (22 degrees C) until both esophageal temperature and mean skin temperature (Tsk) returned to near-baseline values. Subjects then either performed 15 min of cycle ergometry (at 65% maximal oxygen consumption) followed by 30 min of recovery (Exercise), or remained seated with no exercise for 45 min (Control). Subjects were then cooled again. The core temperature thresholds for both vasoconstriction and shivering increased significantly by 0.2 degrees C Post-Exercise (P < 0.05). Because the Tsk at the onset of vasoconstriction and shivering was different during Pre- and Post-Exercise Cooling, we compensated mathematically for changes in skin temperatures using the established linear cutaneous contribution of skin to the control of vasoconstriction and shivering (20%). The calculated core temperature threshold (at a designated skin temperature of 32.0 degrees C) for vasoconstriction increased significantly from 37.1 (0.3) degrees C to 37.5 ( 0.3) degrees C post-exercise (P < 0.05). Likewise, the shivering threshold increased from 36.2 (0.3) degrees C to 36.5 (0.3) degrees C post-exercise (P < 0.05). In contrast to the post-exercise increase in cold thermal response thresholds, sequential measurements demonstrated a time-dependent similarity in the Pre- and Post-Control thresholds for vasoconstriction and shivering. These data indicate that exercise has a prolonged effect on the post-exercise thresholds for both cold thermoregulatory responses.     

Thermoregulation during pentobarbital and ketamine anesthesia in rats

1.) Core temperature, tail temperature, metabolic heat production, and evaporative heat loss were measured in rats exposed to various ambient temperature conditions. 2.) Control rats increased heat production in the cold and heat loss in a warm environment, thus maintaining a relatively constant core temperature. 3.) Pentobarbital anesthesia reduced the thermoregulatory responses and caused core temperature to vary considerably with ambient temperature. Ketamine anesthesia resulted in minor thermoregulatory deficits. 4.) It is concluded that ketamine can be used in thermal physiological studies that require an anesthetised preparation, although it is not completely devoid of inhibitory effects on thermoregulatory responses.     

Development of hypothermia in rats at increase of [Ca2+] in the blood

In rats, data on influence of i. v. administration of calcium chloride on the level of [Ca2+] in the blood and on process of oppression ofthermoregulatory and respiratory functions in rats in hypothermia. 0.18 or 0.135 mmol Ca2+ on the 3rd minute from beginning of the administration increased [Ca2+] in the blood from 1.01 +/- 0.03 to 2.56 +/- 0.08 mM (or 2.27 +/- 0.06 mM). Then [Ca2+] was reduced gradually, in 20 minutes from administration, solution of CaCh [Ca2+] exceeded the initial level by 20-30 %. The increase of concentration of ionized calcium in the rat blood strengthened the cold oppression of breathing and cold shivering as compared with the control (administration of physiological solution). Arrest of breathing in rats after administration of CaCl2 solution occurred at higher rectal temperatures (21 +/- 0.03 degrees C) as compared with control experiments (18 +/- 0.4 degrees C), p < 0.05. It is suggested that increase of [Ca2+] in the blood strengthens effects of cold in the form of oppression of thermoregulatory and respiratory functions.     

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.     

Seasonal changes in thermal responses of urban residents to cold exposure

To determine whether urban circumpolar residents show seasonal acclimatisation to cold, thermoregulatory responses and thermal perception during cold exposure were examined in young men during January-March (n=7) and August-September (n=8). Subjects were exposed for 24 h to 22 and to 10 degrees C. Rectal (T(rect)) and skin temperatures were measured throughout the exposure. Oxygen consumption (VO(2)), finger skin blood flow (Q(f)), shivering and cold (CDT) and warm detection thresholds (WDT) were assessed four times during the exposure. Ratings of thermal sensations, comfort and tolerance were recorded using subjective judgement scales at 1-h intervals. During winter, subjects had a significantly higher mean skin temperature at both 22 and 10 degrees C compared with summer. However, skin temperatures decreased more at 10 degrees C in winter and remained higher only in the trunk. Finger skin temperature was higher at 22 degrees C, but lower at 10 degrees C in the winter suggesting an enhanced cold-induced vasoconstriction. Similarly, Q(f) decreased more in winter. The cold detection threshold of the hand was shifted to a lower level in the cold, and more substantially in the winter, which was related to lower skin temperatures in winter. Thermal sensations showed only slight seasonal variation. The observed seasonal differences in thermal responses suggest increased preservation of heat especially in the peripheral areas in winter. Blunted vasomotor and skin temperature responses, which are typical for habituation to cold, were not observed in winter. Instead, the responses in winter resemble aggravated reactions of non-cold acclimatised subjects.     

Influence of menstrual cycle on shivering, skin blood flow, and sweating responses measured at night

In 10 women, external cold and heat exposures were performed both in the middle of luteal phase (L) and in the early follicular phase (F) of the menstrual cycle. Serum progesterone concentrations in L and F averaged 46.0 and 0.9 nmol X l-1, respectively. The experiments took place between 3:00 and 4:30 A.M., when the L-F core temperature difference is maximal. At neutral ambient temperature, esophageal (Tes), tympanic (Tty), rectal (Tre), and mean skin (Tsk) temperatures averaged 0.59 degrees C higher in L than in F. The thresholds for shivering, chest sweating, and cutaneous vasodilation (heat clearance technique) at the thumb and forearm were increased in L by an average of 0.47 degrees C, related to mean body temperature [Tb(es) = 0.87Tes + 0.13 Tsk] and to Tes, Tty, Tre, or Tsk. The above-threshold chest sweat rate and cutaneous heat clearances at the thumb and forearm were also enhanced in L, when related to Tb(es) or time. The metabolic rate, arm blood flow, and heart rate at thermoneutral conditions were increased in L by 5.0%, 1.1 ml X 100 ml-1 X min-1, and 4.6 beats X min-1, respectively. The concomitant increase in threshold temperatures for all autonomic thermoregulatory responses in L supports the concept of a resetting of the set point underlying the basal body temperature elevation in L. The effects of the increased threshold temperatures are counteracted by enhanced heat loss responses.     

Diabetes mellitus and thermoregulation

Diabetes mellitus is accompanied by a variety of alterations in metabolic, cardiovascular, and neuronal function. This paper provides a comprehensive review of the ways in which these pathophysiological aspects of diabetes may impair thermoregulatory function. The influence of diabetic neuropathy and vasculopathy on the control of peripheral blood flow is reviewed and the additional effects of changing levels of blood glucose and insulin are discussed. Both hypoglycaemia and diabetic ketoacidosis are associated with hypothermia, but the reasons for this in ketoacidosis are not clear. Impairment of heat conservation may contribute to and could be a consequence of autonomic neuropathy. The final section of the paper describes a study of our own in which metabolic stability was maintained by infusing insulin intravenously before and during the determination of the thermoregulatory responses to acute cold stress. Under these conditions, there was impairment of reflex vasoconstriction in the limbs of diabetics with neuropathy. This failure to reduce heat loss resulted in half the diabetics with neuropathy shivering in response to moderate cooling, which in some subjects was accompanied by a fall in core temperature. Diabetics without neuropathy and nondiabetics neither shivered nor dropped core temperature.     

Central alpha-MSH,energy balance,thermal balance,and antipyresis

Intracerebroventricular administration of alpha-MSH in young adult rats enhanced metabolic rate and caused a dose-dependent suppression of food intake, exhibiting a coordinated catabolic pattern. However, the thermoregulatory effects did not seem to be coordinated: the rising heat production was accompanied by a practically simultaneous tendency for rise in heat loss (skin vasodilatation), and the final core temperature either increased or decreased depending on which rise prevailed. The effect on heat loss possibly explains the antipyretic properties of the peptide.     

Mechanisms of suppression of physiological function in hypothermia and a way of their restoration without body warming

It was shown that in hypothermic rats (rectal temperature 25-22 degrees C) it was possible to stimulate responses that had been suppressed by cold (i. e. thermoregulation and breathing) with the aid of injecting a solution of ethylenediaminetetraacetic acid disodium salt (EDTA) in quantity 16.5 mg/100 g of body weight (0.0045 mmol/100 g) into the blood stream of the cooled animals. EDTA connects calcium ions in blood and forms complexes. It was shown that enhancement of cold shivering intensity and that of breathing (in 5 min after beginning the injection of EDTA) coincided with a 42-45 % reduction of [Ca2+] in the blood]. After 15 min following the beginning of injection of EDTA [Ca2+] into the blood stream, a return to the initial level was observed in cooled animals. Simultaneously we observed suppression of the cold shivering and breathing. The repeated injection of EDTA again caused similar fall of [Ca2+] in the blood and the following enhancement of cold shivering and breathing.     

Hypothalamic mechanisms in thermoregulation

Certain preoptic and rostral hypothalamic neurons are sensitive to changes in local preoptic temperature (Tpo). These neurons also receive much afferent input from peripheral thermoreceptors and control a variety of thermoregulatory responses. In thermode-implanted animals, preoptic warming increases the firing rate in warm-sensitive neurons and elicits heat loss responses such as panting and sweating. Preoptic cooling increases the firing rate in cold-sensitive neurons and elicits, first, heat retention responses (e.g., cutaneous vasoconstriction and thermoregulatory behavior), then heat production responses (e.g., shivering and nonshivering thermogenesis). It is likely that the preoptic thermosensitive neurons control these thermoregulatory responses because both respond similarly to changes in Tpo and skin temperature. Specifically, skin warming not only increases panting, skin blood flow, and the firing rate of warm-sensitive neurons, but also decreases the sensitivity of all these responses to Tpo changes. Skin cooling not only increases metabolic heat production, heat retention behavior, and the firing rate of cold-sensitive neurons, but also increases the hypothalamic thermosensitivity of all these responses. Low-firing warm-sensitive neurons receive little afferent input and are most sensitive to high Tpo. Many of these low-firing neurons probably serve in controlling heat loss responses. High-firing warm-sensitive neurons receive much excitatory afferent input and are usually sensitive only to low Tpo. These neurons probably exert their greatest influence on heat production responses, possibly by inhibiting and, thus, determining the thermosensitive characteristics of nearby cold-sensitive neurons.     

Effects of passive heat adaptation and moderate sweatless conditioning on responses to cold and heat

Two series of experiments were performed in physically untrained subjects. In series A (heat adaptation, HA), seven male subjects were adapted to dry heat (five consecutive days at 55 degrees C ambient air temperature (Ta) for 1 h X day-1) under resting conditions. Before and after HA, the subjects' shivering responses were determined in a cold test (Ta + 10 to 0 degrees C). In series B, eight male subjects underwent mild exercise training (five consecutive days at a heart rate, HR, of 120 b X min-1) under Ta conditions individually adjusted (Ta + 15 to +5 degrees C) to prevent both sweating and cold sensations. Before and after "sweatless training", the subjects were subjected to a combined cold and heat test. During HA the thresholds for shivering, cutaneous vasodilatation (thumb and forearm) and sweating were shifted significantly (p less than 0.05) towards lower mean body temperatures (Tb). The mean decrease in threshold Tb was 0.36 degrees C. "Sweatless training" resulted in a mean increase in work rate (at HR 120 b X min-1) and oxygen pulse of 13 and 8%, respectively. However, "sweatless training" did not change the threshold Tb for shivering or sweating. Neither HA nor "sweatless training" changed the slopes of the relationships of shivering and sweating to Tb. It is concluded that the previously reported lowering of shivering and sweating threshold Tb in long-distance runners is not due to an increased fitness level, but is essentially identical with HA. The decreased shivering threshold following HA is interpreted as "cross adaptation" produced by the stressors cold and heat.     

Physical fitness and thermoregulatory reactions in a cold environment in men

The relationship between the physical fitness level (maximal O2 consumption, VO2max) and thermoregulatory reactions was studied in 17 adult males submitted to an acute cold exposure. Standard cold tests were performed in nude subjects, lying for 2 h in a climatic chamber at three ambient air temperatures (10, 5, and 1 degrees C). The level of physical fitness conditioned the intensity of thermoregulatory reactions to cold. For all subjects, there was a direct relationship between physical fitness and 1) metabolic heat production, 2) level of mean skin temperature (Tsk), 3) level of skin conductance, and 4) level of Tsk at the onset of shivering. The predominance of thermogenic or insulative reactions depended on the intensity of the cold stress: insulative reactions were preferential at 10 degrees C, or even at 5 degrees C, whereas colder ambient temperature (1 degree C) triggered metabolic heat production abilities, which were closely related to the subject's physical fitness level. Fit subjects have more efficient thermoregulatory abilities against cold stress than unfit subjects, certainly because of an improved sensitivity of the thermoregulatory system.     

About a correlation between calcium ion concentration (Ca2+) in the blood and the state of physiological functions in animals in deep cooling

The changes in physiological functions of the organism (respiration, functions of the heart and vessels, thermoregulation) were studied. The concentration of Ca2+ ions in the blood of white rats was determined by the ion-selective electrodes at various stages of hypothermia. The aim of the study was to reveal changes in the blood concentration of ionized calcium in animals during their gradual cooling. In deep hypothermia (16 degrees C), calcium ion concentration in the blood increased by 30% against the norm which coincides with arrest of the cold shivering and lung ventilation. An increased content of Ca2+ in the blood is supposed to result in an increase in the content of these ions in the intercellular liquid and in the nervous cells, which is one of the reasons for the cold paralysis of the respiration and thermoregulation centers.     

Relationship of osmotic inhibition in thermoregulatory responses and sweat sodium concentration in humans

Heat acclimatization improves thermoregulatory responses to heat stress and decreases sweat sodium concentration ([Na(+)](sweat)). The reduced [Na(+)](sweat) results in a larger increase in plasma osmolality (P(osmol)) at a given amount of sweat output. The increase in P(osmol) inhibits thermoregulatory responses to increased body core temperature. Therefore, we hypothesized that the inhibitory effect of plasma hyperosmolality on the thermoregulatory responses to heat stress should be attenuated with the reduction of [Na(+)](sweat) due to heat acclimatization. Eleven subjects (9 male and 2 female) were passively heated by immersing their lower legs into water at 42 degrees C (room temperature 28 degrees C and relative humidity 30%) for 50 min following isotonic or hypertonic saline infusion. We determined the increase in the esophageal temperature (T(es)) required to elicit sweating and cutaneous vasodilation (CVD) (DeltaT(es) thresholds for sweating and CVD, respectively) in each condition and calculated the elevation of the T(es) thresholds per unit increase in P(osmol) as the osmotic inhibition of sweating and CVD. The osmotic shift in the DeltaT(es) thresholds for both sweating and CVD correlated linearly with [Na(+)](sweat) (r = 0.858 and r = 0.628, respectively). Thus subjects with a lower [Na(+)](sweat) showed a smaller osmotic elevation of the DeltaT(es) thresholds for sweating and CVD. These results suggest the possibility that heat acclimatization attenuates osmotic inhibition of thermoregulatory responses as well as reducing [Na(+)](sweat).     

Effects of repeated short-term cold exposures on cold induced thermogenesis of women

The effects of repeated exposures to resting cold air (10°C) on the shivering and thermogenic responses of women to standard cold stress were investigated. Ten women, aged 18 to 34 years, were divided into two groups of five women each. One group, the acclimated (A) was exposed ten times within 2 weeks, the first and the last exposures being the pre-and post-tests respectively. The second group, the control (C) was exposed twice within 18 days. Measurements of rectal and skin temperatures, oxygen uptake, time to onset of shivering (TOS), and perceived cold were performed during all exposures. Shivering responses were evaluated by electromyography and visually. A significant (P<0.05), increase was seen in TOS (from 26.2 min to 55.6 min), and a significant decrease was seen in thermoregulatory heat production (from 14.78 kcal/h to –2.64 kcal/h) in group A; these changes were evident after about five exposures. It is concluded that the women became cold acclimated as a result of the repeated short-term resting cold air exposures.Research supported by Capes/Brazil, and by the Universidade Federal de Minas Gerais/Brazil     

Agonist of TRPM8 channel,menthol, facilitates the initiation of thermoregulatory responses to external cooling

The effects of activation of the cold and menthol sensitive TRPM8 ion channel on different thermoregulatory parameters (total oxygen consumption, carbon dioxide release, respiratory coefficient, vasoconstriction response of skin blood vessels and shivering) were studied in anaesthetized rats subjected to two types of external cooling—rapid and slow.     

Arginine vasopressin does not mediate heat loss in the tail of the rat

It has been reported that hypothermia induced by arginine vasopressin (AVP) is brought about by a coordinated response of reduced thermogenesis in brown adipose tissue (BAT) and increased heat loss through the tail of rats. However, it is well known that AVP is one of the strongest peripheral vasoconstrictors. Whether the AVP-induced hypothermia is associated with an increase in heat loss through the tail is questionable. Therefore, the present study assessed the relationship between the effects of AVP on tail skin temperature and the induced hypothermic response, and to determine if peripheral AVP administration increases heat loss from the tail. Core, BAT and tail skin temperature were monitored by telemetry in male Sprague–Dawley rats before and after intraperitoneal administration of AVP or vasopressin receptor antagonist. We also analyzed simultaneously of the time-course of AVP-induced hypothermic response and its relationship with changes in BAT temperature, and effect of AVP on grooming behavior. The key observations in this study were: (1) rats dosed with AVP induced a decrease in heat production (i.e., a reduction of BAT thermogenesis) and an increase of saliva spreading for evaporative heat loss (i.e., grooming behavior); (2) AVP caused a marked decrease in tail skin temperature and this effect was prevented by the peripheral administration of the vasopressin V1a receptor antagonist, suggesting that exogenous AVP does not increase heat loss in the tail of rats; (3) the vasopressin V1a receptor antagonist could elevate core temperature without affecting tail skin temperature, suggesting that endogenous AVP is involved in suppression of thermogenesis, but not mediates heat loss in the tail of rats. Overall, the present study does not support the conclusion of previous reports that AVP increased tail heat loss in rats, because AVP-induced hypothermia in the rat is accompanied by a decrease in tail skin temperature. The data indicate that exogenous AVP-induced hypothermia attributed to the suppression of thermoregulatory heat production and the increase of saliva spreading for evaporative heat loss.