Thermoregulatory Effects Research Articles

94312952 The thermoregulatory effects of menopausal hot flashes on sleep

94312952 The thermoregulatory effects of menopausal hot flashes on sleep

Midazolam minimally impairs thermoregulatory control.

Perioperative hypothermia usually results largely from pharmacologic inhibition of normal thermoregulatory control. Midazolam is a commonly used sedative and anesthetic adjuvant whose thermoregulatory effects are unknown. We therefore tested the hypothesis that midazolam administration impairs thermoregulatory control. Eight volunteers were studied on 2 days each, once without drug and once at a target total plasma midazolam concentration of 0.3 micrograms/mL (corresponding to administration of approximately 40 mg over approximately 4 h). Each day, skin and core temperatures were increased sufficiently to provoke sweating, and then reduced to elicit peripheral vasoconstriction and shivering. We mathematically compensated for changes in skin temperature using the established linear cutaneous contributions to control of each response. From these calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C), we determined the thermoregulatory effects of midazolam. The sweating threshold was decreased approximately 0.3 degrees C by midazolam administration: 37.3 +/- 0.2 degrees C vs 37.0 +/- 0.3 degrees C (P = 0.0004, paired t-test). Midazolam decreased the core temperature that triggered vasoconstriction somewhat more: 37.1 +/- 0.2 degrees C vs 36.3 +/- 0.5 degrees C (P = 0.0002). Similarly, midazolam decreased the shivering threshold: 35.9 +/- 0.3 degrees C vs 35.3 +/- 0.6 degrees C (P = 0.03). The sweating-to-vasoconstriction (interthreshold) range, therefore, increased from 0.2 +/- 0.1 degrees C to 0.7 +/- 0.3 degrees C (P = 0.002). Although statistically significant, this relatively small increase contrasts markedly with the 3-5 degrees C interthreshold ranges produced by clinical doses of volatile anesthetics, propofol, and opioids.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil slightly increases the sweating threshold and markedly reduces the vasoconstriction and shivering thresholds.

Hypothermia is common in surgical patients and victims of major trauma; it also results from environmental exposure and drug abuse. In most cases, hypothermia results largely from drug-induced inhibition of normal thermoregulatory control. Although opioids are given to a variety of patients, the thermoregulatory effects of opioids in humans remain unknown. Accordingly, the hypothesis that opioid administration impairs thermoregulatory control was tested. Eight volunteers were studied, each on 3 days: (1) a target total plasma alfentanil concentration of 100 ng/ml, (2) control (no drug), and (3) a target alfentanil concentration of 300 ng/ml. Each day, skin and core temperatures were increased sufficiently to provoke sweating. Temperatures subsequently were reduced to elicit peripheral vasoconstriction and shivering. Mathematical compensations were made for changes in skin temperature using the established linear cutaneous contributions to control of sweating (10%) and to vasoconstriction and shivering (20%). From the calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C) and unbound plasma alfentanil concentrations, the individual concentration-response relationship was determined. The concentration-response relationship for all the volunteers was determined similarly using total alfentanil concentrations. In terms of unbound concentration, alfentanil increased the sweating threshold (slope = 0.021 +/- 0.016 degrees C.ng-1.ml; r2 = 0.92 +/- 0.06). Alfentanil also significantly decreased the vasoconstriction (slope = -0.075 +/- 0.067 degrees C.ng-1.ml; r2 = 0.92 +/- 0.07) and shivering thresholds (slope = -0.063 +/- -0.037 degrees C.ng-1.ml; r2 = 0.98 +/- 0.04). In terms of total alfentanil concentration (degrees C.ng-1.ml), the sweating threshold increased according to the equation: threshold (degrees C) = 0.0014[alfentanil] + 37.2 (r2 = 0.33). In contrast, alfentanil produced a linear decrease in the core temperature, triggering vasoconstriction: threshold (degrees C) = -0.0049[alfentanil] + 36.7 (r2 = 0.64). Similarly, alfentanil linearly decreased the shivering threshold: threshold (degrees C) = -0.0057[alfentanil] + 35.9 (r2 = 0.70). The observed pattern of thermoregulatory impairment is similar to that produced by most general anesthetics: a slight increase in the sweating threshold and a substantial, linear decrease in the vasoconstriction and shivering thresholds.

Effects of epinephrine on thermoregulatory behavior in lean and obese Zucker rats in the cold

This series of experiments examined whether epinephrine (EPI) produces the same thermoregulatory effects in the cold that have been reported for norepinephrine and isoproterenol. Lean and obese Zucker rats were trained to press a lever to activate infrared heat lamps in a cold (−8 °C) environment. Operant thermoregulatory behavior increased dose-dependently following EPI (0–100 μg/kg), but posttest colonic temperature (Tc) fell. Thermal balance calculations showed a substantial increase in net heat loss, more so in obese than lean animals. EPI is therefore thermolytic—i.e., disrupts thermal balance. A low dose (100 μg/kg) of the α-antagonist phentolamine produced a marked improvement in operant behavior, Tc, and thermal balance, whereas a comparable dose of the β-antagonist propranolol had no beneficial effect. Increasing the dose of phentolamine worsened the responses with respect to the 100-μg/kg dose. The selective α 1-antagonist prazosin ameliorated the decrease in Tc induced by EPI but had little effect on operant behavior or thermal balance; the selective α 2-antagonist yohimbine had no effect on any parameter compared to EPI alone. These results suggest that the paradoxical effects of EPI in the cold are mediated by α-adrenoceptors, but definitive identification of the subclass of receptor involved cannot be determined.

Effect of administration of angiotensin II and isoproterenol, alone and in combination, on drinking and tail skin temperature of the rat

Both angiotensin II (AII) and the β-adrenergic agonist isoproterenol are well known to induce drinking and increase tail skin temperature (T SK) in rats. Previous studies have shown that these two compounds have an additive, rather than interactive, dipsogenic effect when administered together. The present studies confirmed the additivity of the dipsogenic effect of the two compounds and attempted to extend these results to T SK. The results reveal that at a series of dosage combinations of AII [100 and 125 μg/kg, subcutaneously (SC)] and isoproterenol (ISOP) (10, 12.5, and 25 μg/kg, SC) administered together, the increase in T SK usually induced by each compound was canceled. This occurred at the two lower doses of ISOP in combination with AII. Thus, the differences between dipsogenic and thermoregulatory effects of combined doses of AII and ISOP suggest a difference in central integration. Important differences between the thermoregulatory responses to administration of the two compounds include increases in metabolic rate and colonie temperature when ISOP is administered and decreases in both when AII is administered. It is suggested that the effect of the two compounds to cancel each other with respect to T SK is related to their opposite effects on metabolic rate.

Thermoregulatory effects of alkaloids isolated from Wu-chu-yu in afebrile and febrile rats

Dehydroevodiamine (DeHE) and evodiamine (EVO), alkaloids isolated from a Chinese medicinal herb, Wu-chu-yu, exhibit calcium antagonistic activity. Intraperitoneal injections of DeHE (5–20 mg/kg) and EVO (2.5–10 mg/kg) caused a dose-related hypothermia in afebrile rats at an ambient temperature (Ta) of 20 °C. Because the heat production of alkaloid-injected rats did not differ from that of the controls, the hypothermic effect likely resulted from increased peripheral heat loss. This suggestion is supported by the finding that both DeHE and EVO did not affect the thermoregulatory response of rats exposed to a Ta of 35 °C, at which heat loss was maximized. Injection of the same doses of DeHE and EVO attenuated the febrile response in a dose-related manner, induced by intrahypothalamic injection of exogenous pyrogen. The attenuation of the febrile response was associated with a reduction in heat production. Because DeHE and EVO did not affect HP in afebrile rats at a Ta of either 20 or 35 °C, but suppressed the metabolic rate of febrile rats at 20 °C, the thermoregulatory effect of DeHE and EVO could involve both a calcium-dependent increase in heat loss and a suppression in heat production; the latter may only be manifested when the set point for thermoregulation is elevated.

Biochemical and Thermoregulatory Effects of Behavioral Treatment for Menopausal Hot Flashes

Although hormone replacement therapy is an effective treatment for menopausal symptoms, it is contraindicated for some women with an increased risk of cancer. It has previously been shown that postmenopausal women with hot flashes have elevated levels of central sympathetic activation. We therefore developed a behavioral relaxation procedure that significantly reduced hot flash frequency, presumably through the reduction of central sympathetic activation. Twenty-four postmenopausal women with at least five hot flashes per day were randomly assigned to receive eight 1-h sessions of training in paced respiration or alpha-EEG biofeedback (placebo). Pre- and posttreatment assessments of respiratory parameters and measurements of plasma 3-methoxy-4-hydroxyphenylglycol (MHPG: the main metabolite of brain norepinephrine), norepinephrine, epinephrine, and platelet α2-adrenergic receptors were performed. Ambulatory monitoring of skin conductance level and tidal volume (24 h) were used to assess the effects of treatment. Hot flash frequency declined significantly(p <0.001) for the paced-respiration group (9.5 ± 1.4/day pre vs. 5.5 ± 1.5 post) but not for the placebo group. There were no significant changes in any biochemical measure. In addition to the decline in hot flash frequency, the 24-h pattern of skin-conductance level was significantly altered for the paced respiration group. Thus the effects of paced respiration training do not appear to be mediated through reduced sympathetic activation but do result in thermoregulatory changes over a 24-h period.

Biochemical and Thermoregulatory Effects of Behav-ioral Treatment for Menopausal Hot Flashes

Biochemical and Thermoregulatory Effects of Behav-ioral Treatment for Menopausal Hot Flashes

Additive hypothermic effects of cocaine and nicardipine in guinea-pigs

1. 1. This study investigated the thermoregulatory effects of cocaine combined with two reported antidotal treatments for acute cocaine overdosage, calcium channel blocker therapy and cold ambient temperatures. 2. 2. Cocaine and nicardipine alone lowered the core temperature of female guinea-pigs (ambient temperature, 5°C) which resulted in a drop in core temperature of approximately 2°C at their highest respective doses (40 mg/kg and 50 mg/kg). 3. 3. Nicardipine administration 30 min prior to cocaine caused an almost 2-fold drop in temperature (3.75°C) relative to either drug alone. 4. 4. The data suggest that cocaine and nicardipine produce hypothermia by different, but additive, mechanisms.

Thermoregulatory effects of resiniferatoxin in the rat

When administered acutely, the vanilloid (capsaicin) receptor agonist resiniferatoxin induces marked hypothermia in the ferret, rat and mouse. The aim of this study was to further characterise the thermoregulatory effects of resiniferatoxin in the rat in an attempt to understand the mechanism by which resiniferatoxin induces this hypothermic effect. Three doses of resiniferatoxin were administered (50, 100, 200 μg/kg s.c.) in separate animals at an ambient temperature ( T a) of 20°C but there was no apparent dose-related effect on the decrease in colonic temperature over this range. Resiniferatoxin (50 μg/kg s.c.) decreased whole body oxygen consumption when measured below thermoneutrality ( T a = 20°C) but not at thermoneutrality ( T a = 29°C); likewise there was no hypothermic response to resiniferatoxin when measured at a T a of 29°C. Operant responding for radiant heat in a cold environment (−8°C) was also measured in resiniferatoxin-treated (50 μg/kg s.c.) rats. These experiments showed that resiniferatoxin-treated rats attempted to defend body temperature by lever pressing for more radiant heat. However, this was not sufficient to reverse the hypothermia. Two repeat doses, 1 week apart, had little or no effect on colonic temperature, oxygen consumption or operant responding in the cold. Resiniferatoxin (50 μg/kg s.c.) also produced hypothermia ( T a = 20°C) in neonatally capsaicinized adult rats. The exact site and mode of action is still under investigation, but it is postulated that resiniferatoxin activates, and then destroys or desensitizes warm thermoreceptors.

Effects of estrogen on thermoregulatory evaporation in rats exposed to heat

The purpose of this study was to determine the effects of estrogen (E2) replacement on thermoregulation in ovariectomized rats exposed to heat. Female Sprague-Dawley rats were ovariectomized and splenectomized and implanted with a temperature-sensitive transmitter. Each rat was studied when E2 treated (after an E2 pellet implant) and untreated. Animals were divided into two groups with opposite order of treatment and were studied over a 9-wk period. Measurements of body core temperature (Tc) and evaporative water loss (EWL) were made on unrestrained animals resting at 38 degrees C air temperature. E2-treated animals increased EWL at all levels of Tc, reduced the threshold Tc for onset of saliva spreading, and regulated Tc at a lower level during heat exposure. E2 treatment elevated plasma E2 and reduced hematocrit but did not affect plasma osmolality. These effects of E2 on evaporative cooling and Tc in heat-stressed rats are similar to those that have been reported in human females. The mechanisms of the thermoregulatory effects of E2 remain to be studied.

The Thermoregulatory Effects of Menopausal Hot Flashes on Sleep

Menopausal hot flashes are thought to be a disorder of thermoregulation initiated centrally within the medial preoptic area of the hypothalamus. These heat-loss mechanisms appear to be activated in the presence of normal core body temperature. Previous studies have demonstrated that thermal stimuli have the potential to alter sleep stages. We performed 24-hour ambulatory recordings of hot flashes and all-night sleep parameters on 12 postmenopausal women with hot flashes and seven postmenopausal women without flashes to determine whether the presence of hot flashes prior to sleep or during sleep itself would result in alterations in sleep pattern. The results show that hot flashes are associated with increased Stage 4 sleep and a shortened first rapid eye movement period. Hot flashes occurring in the 2 hours prior to sleep onset were positively correlated with the amount of slow-wave sleep. The central thermoregulatory mechanism underlying hot flashes may affect hypnogenic pathways inducing sleep and heat loss in the absence of a thermal load.

Pyridostigmine bromide does not alter thermoregulation during exercise in cold air

This study examined the effects of acute and chronic pyridostigmine bromide (PB) administration on thermoregulatory and metabolic responses to exercise in cold air (5 degrees C). Seven healthy men completed two 7-day trials in a double-blind, crossover experimental design: during one trial they received PB (30 mg three times daily) and during the other trial they received placebo. For each trial, subjects attempted four (3 h) exercise tests: low-intensity exercise (approximately 25% VO2max) and moderate-intensity exercise (approximately 50% VO2max), on days 2 and 3 and again on days 6 and 7. Metabolic rate, body temperatures, and venous blood samples were obtained before and during exercise. Red blood cell acetylcholinesterase inhibition induced by PB increased (p < 0.05) from 34% on day 1 to 43% on days 3-7. Metabolic rate, body temperatures, and regional heat conductance responses were not different between trials. Plasma glucose, glycerol, free fatty acid, lactate, sodium, and potassium concentrations were not different between trials. In addition, differences were not found between acute and chronic experiments for any thermoregulatory or metabolic responses. These findings demonstrate that the PB dosage used by military personnel, as a pharmacological defense against nerve-agent poisoning, should not cause any adverse thermoregulatory or metabolic effects during moderate activity in cold climates.

Interactions between cellular respiration and thermoregulation in the paramecium.

An important adaptation to hypoxia is a regulated reduction in body temperature because it lowers metabolic rate when oxygen supply is limited. Although this beneficial response occurs in organisms ranging from protozoans to mammals, little is known of the cellular mechanisms responsible for the hypoxia-induced reduction in temperature. Using the unicellular protozoan, Paramecium caudatum, we showed that inhibition of oxidative phosphorylation with sodium azide (NaN3) under normoxic conditions mimics the thermoregulatory effects of hypoxia, causing this species to select a lower temperature in a thermal gradient (P < 0.0001). Under control conditions, selected temperature (Tsel) was 28.3 +/- 0.3 degrees C. NaN3 concentrations of 0.1 mM and above significantly reduced Tsel (P < 0.0001). Ten millimolar NaN3 produced the maximal reduction in Tsel, 11.4 degrees C, and the dose that produced 50% of the maximal response was 0.7 mM. The reduction in temperature was beneficial because both O2 consumption and survival were significantly less affected by NaN3 at lower temperatures. These results suggest that O2 does not directly affect thermoregulation in the paramecium. Rather, the hypoxia-induced reduction in Tsel results from inhibition of oxidative phosphorylation.

Autonomic and behavioral thermoregulation in the golden hamster during subchronic administration of clorgyline

Chronic administration of glorgyline, a type-A monoamine oxidase inhibitor, leads to a decrease inperitoneal (i.e., core) temperature of golden hamsters. To better understand the mechanisms of clorgyline's thermoregulatory effects, autonomic and behavioral thermoregulatory effectors were measured in Syrian hamsters following chronic infusion of clorgyline via a minipump (2 mg/kg/day). Metabolic rate, evaporative water loss, motor activity, and core temperature were measured after 60 min of exposure to ambient temperatures ( T a) of 5, 20, 30, and 35°C. Behavioral thermoregulatory responses were assessed by measuring selected T a and motor activity of the same animals in a temperature gradient over the course of 23 h. Metabolic rate and motor activity were significantly elevated in clorgyline-treated hamsters exposed to a T a of 5°C. There were no effects of clorgyline on evaporative water loss. In the temperature gradient the mean selected T a of clorgyline-treated hamsters was nearly equal to that of the saline-treated hamsters, 30.7 and 31.2°C, respectively. On the other hand, the mode of selected T a in the clorgyline group was 2.8°C higher than that of the saline group. Motor activity in the gradient was significantly elevated and food consumption was depressed by clorgyline treatment. Overall, these findings indicated the chronic clorgyline treatment in the golden hamsters results in novel autonomic and behavioral modification; it stimulates metabolic thermogenesis during cold exposure, but appears to increase the behavioral zone of thermoneutrality. This latter effect may mean an improvement in heat tolerance, suggesting that this drug might assist in the adaptation to warm temperatures.

Thermoregulatory Effects of Ergovaline Isolated from Endophyte-Infected Tall Fescue Seed on Rats

Ergovaline (EV) was isolated from Acremonium coenophialum-infected tall fescue seed. Seed (2 kg) was extracted with 20 L of 5% lactic acid in water/methanol (4:1), filtered, and passed over an Amberlite XAD-2 column. Ergovaline was eluted with MeOH, concentrated, and chromatographed on two reversed-phase C 18 columns (purity >95%, 40% overall recovery). It was administered to rats (15 μg/kg of BW, ip) at 22 o C to determine time-related acute effects on thermoregulatory ability

Cholecystokinin octapeptide (CCK-8) injected into a cerebral ventricle induces a fever-like thermoregulatory response mediated by type B CCK-receptors in the rat

In conscious female Wistar rats with chronic lateral cerebroventricular cannula, the thermoregulatory effects of CCK-8, ceruletide and prostaglandin E 1 (PGE 1) were studied. In addition, the possible involvement of type A or type B receptors of CCK-8 in thermoregulatory effects of PGE 1 and CCK-8 was also investigated. In the normothermic rat an intracerebroventricular (i.c.v.) injection of CCK-8 or ceruletide induced a thermogenic response with tail-skin vasoconstriction and a resulting rise in colonic temperature (T c). There was a significant negative correlation between the starting level of T c and the extent of rise in T c following an i.c.v. administration of PGE 1, CCK-8 or ceruletide. Subcutaneously injected CCK-8 caused decreases in T c in a cool ambient temperature as also described by others. The fever-like response to i.c.v. injected CCK-8 was attenuated by a CCK type B receptor blocker, but not by a CCK type A receptor blocker. Conversely, the hypothermic response to peripherally administered CCK-8 was attenuated by a type A receptor blocker, but not by a type B receptor blocker. Neither of these CCK-receptor blockers influenced the fever caused by an i.c.v. injection of PGE 1. It is concluded that in normothermic rats the thermogenic response observed after i.c.v. injection of CCK-8 and ceruletide is the most likely central thermoregulatory change mediated by CCK type B receptors, while the well-known hypothermic response observed after peripheral injection of these peptides might also be explained by their direct effect on variables influencing some of the thermoregulatory effector mechanisms at the periphery.

Thermoregulatory effect of intracerebral injections of neuropeptide Y in rats at different environmental temperatures

1. 1. In order to characterize the thermoregulatory actions of brain neuropeptide Y (NPY), the effects of intra-third ventricular (I3V) injection of NPY on temperatures of colon ( T co), brown adipose tissue ( T BAT) and tail skin ( T s) were observed at ambient temperatures ( T a) of 19 and 8°C. 2. 2. The injection of NPY in a dose of 8 mcg/100 g body wt evoked a fall of T co by about 2°C in both neutral and cold environments. NPY (4 and 8 mcg/100 g body wt) induced dose-dependent T co falls in rats at thermoneutral environment. The thermolytic reactions induced by I3V administration of NPY were associated with a fall in T BAT but no changes in I s were observed. 3. 3. The results suggest that NPY may mediate hypothermic response in neutral and cold environments mainly by its effects on the brown adipose tissues in the rat.

Thermoregulatory effects of chlorpyrifos in the rat: Long-term changes in cholinergic and noradrenergic sensitivity

Subcutaneous injection of a sublethal dose of chlorpyrifos (CHLP), an organophosphate (OP) pesticide, causes long-term inhibition in cholinesterase activity (ChE) of brain, blood, and other tissues. Such prolonged inhibition in ChE should lead to marked behavioral and autonomic thermoregulatory patterns, especially in terms of altered noradrenergic and cholinergic sensitivity. To evaluate the behavioral and autonomic effects of long-term ChE inhibition, Long-Evans rats were implanted with radiotelemetry transmitters that continuously monitored core temperature (Tc), heart rate (HR), and motor activity (MA). These parameters were monitored for 7 days following a single injection of peanut oil (vehicle control) or 280 mg/kg CHLP. CHLP led to a significant reduction in Tc during the first night after treatment but had no other effects on Tc. CHLP also resulted in a significant elevation in HR which lasted for ∼72 h. Motor activity was unaffected by CHLP. Cholinergic and noradrenergic drug sensitivity was assessed between 7 and 25 days after CHLP. CHLP-treated rats were more sensitive to norepinephrine as based on a greater hyperthermic response. MA of CHLP-treated rats was more sensitive to scopolamine. On the other hand, the hypothermic effects of oxotremorine (0.4 mg/kg) were nearly abolished by CHLP treatment, indicating tolerance to cholinergic stimulation. The tachycardic effects of methylscopolamine were also greater in the CHLP group. Overall, the acute effects of CHLP are unusual compared to other OP's in that there is no hypothermic response, an attenuated nocturnal elevation in Tc and a prolonged elevation in HR. The CHLP treated rat exhibits a prolonged elevation in HR, hypersensitivity to noradrenergic stimulation and cholinergic antagonism but hyposensitivity to central cholinergic stimulation.

Comparison between thermoregulatory effects mediated by α1- and α2-adrenoceptors in normothermic and febrile rabbits

1. 1. In order to better delineate the profile of thermoregulatory action of α 1-adrenoceptor antagonists; corynanthine (CRN) and BMY 20064 (BMY), and α 2-adrenoceptor agonist; medetomidine (MDT) and B-HT 920 (BHT), the effect of intravenous administration of two doses of these drugs on rectal ( T re) and ear skin ( T e) temperatures, metabolic rate ( M), respiratory evaporative heat loss ( E res) and respiratory rate ( R r) were examined in febrile and non-febrile rabbits. 2. 2. Results indicate that α 1-adrenoceptor antagonists as well as α 2-adrenoceptor agonists markedly lowered body temperature exhibiting antipyretic and hypothermic actions. The hypothermic and antipyretic effect after the CRN or BMY, and BHT or MDT, treatment was associated with inhibition of metabolic rate and/or with body heat redistributed to peripheral tissues and an increase of the potential for heat loss to the environment. 3. 3. BMY also abolished the thermogenic response to cold. However, BMY did not affect metabolic heat production on exposure to a cold ambient temperature. This unexpected phenomenon is difficult to explain at the present moment. Possible mechanisms responsible for the thermoregulatory activity of BMY are discussed. 4. 4. These results indicate that α 1- and α 2-adrenoceptor drugs' thermoregulatory actions are similar in event and suggest that both subtypes of α-adrenoceptor might be implicated functionally in a variety of thermoregulatory processes.