Heart rate variability and electrocardiogram waveform as predictors of morbidity during hypothermia and rewarming in rats.

This study examined electrocardiogram (ECG) waveform, heart rate (HR), mean blood pressure (BP), and HR variability as potential autonomic signatures of hypothermia and rewarming. Adult male Sprague-Dawley rats had telemetry transmitters surgically implanted, and 2 weeks were allowed for recovery prior to induction of hypothermia. Rats were lightly anesthetized (sodium pentobarbital, 35 mg/kg i.

Tissue-specific extravasation of albumin-bound Evans blue in hypothermic and rewarmed rats.

The effects of hypothermia and rewarming on endothelial integrity were examined in intestines, kidney, heart, gastrocnemius muscle, liver, spleen, and brain by measuring albumin-bound Evans blue loss from the vasculature. Ten groups of twelve rats, normothermic with no pentobarbital, normothermic sampled at 2, 3, or 4 h after pentobarbital, hypothermic to 20, 25, or 30 degrees C, and rewarmed from 20, 25, or 30 degrees C, were cooled in copper coils through which water circulated. Hypothermic rats were cooled to the desired core temperature and maintained there for 1 h; rewarmed rats were cooled to the same core temperatures, maintained there for 1 h, and then rewarmed.

Comparison of oxygenated perfluorocarbon and humidified oxygen for rewarming hypothermic miniswine.

This study examines a method to rapidly rewarm the core using total liquid ventilation with warmed, oxygenated perfluorocarbon. Yucatan miniswine were splenectomized and surgically implanted with telemetry devices to transmit electrocardiographic response, arterial pressure, and core temperature. Hypothermia (core temperature = 25.

Treatment of hyperthermia-induced extravasation with hypertonic saline (7.5%) in 6% dextran 70 (HSD) in Wistar/Furth rats.

This study determined the effectiveness of hypertonic saline (7.5%) in 6% Dextran 70 (HSD) in reducing hyperthermia-induced extravasation in Wistar/Furth (WF) rats and compared this extravasation with that previously reported in Sprague-Dawley (SD) rats. Wistar/Furth rats (male, n = 12/group, 300-325 g) were placed unrestrained in a chamber (41.

Flunarizine pretreatment attenuates hyperthermia-induced extravasation in rats.

Previous work has established that there is an increase in endothelial permeability in hyperthermic rats. This work assessed the potential of the calcium channel blocker (E)-1-bis(4-fluorophenyl)methyl-4-(3-phenyl-2-propenyl)piperazine dihydrochloride (flunarizine) as a pretreatment to ameliorate this extravasation. Five groups of male rats (n=12 rats per group, 400-500 g) were given 0, 0.

Effect of nitric oxide synthase inhibition on regional blood flow during hyperthermia.

The loss of compensatory splanchnic vasoconstriction during hyperthermia was assessed in rats after administration of either 0, 10, 30, or 100mg/kg N(w)-nitro-L-arginine methyl ester,L-NAME. Rectal temperature (T(re)), heart rate (HR), mean arterial blood pressure (MAP), breathing frequency (BF), and renal, mesenteric and caudal blood flows (Q(R), Q(M) and Q(C)) were measured until irreversible cardiovascular collapse occurred. HR, MAP and BF increased as T(re) rose to 42 degrees C, then fell as circulatory collapse occurred.

Hyperthermic effects on reticuloendothelial system particulate uptake.

Reticuloendothelial system (RES) particulate uptake (PU) of vascular debris influences survival from extreme hyperthermia. Little is known of the effect of extreme hyperthermia, unrelated to fever, on RES PU shortly after reaching a maximum core temperature (T(c)). Relative to normothermic rats (T(c)=38.

Hyperthermia-induced changes in the vascular permeability of rats: a model system to examine therapeutic interventions.

Extravasation in the heart, liver, lung, kidney, spleen, gastrocnemius, and duodenum was quantified in normothermic and hyperthermic (core temperature (T(c))=41.5, 42, or 42.6 degrees C) rats.

Telemetry augments the validity of the rat as a model for heat acclimation.

Repeated exposure to heat stress results in physiological adaptations which increase tolerance to heat stress. Core temperature (Tc) and heart rate (HR), two indices of successful heat acclimation, are both increased by the handling and restraint usually required to measure these variables in the rat. This study compares measurement of these variables in telemetry- and nontelemetry-equipped heat-acclimated rats.

Treatment of hyperthermia and dehydration with hypertonic saline in dextran.

Hyperthermia may be accompanied by dehydration with or without electrolyte loss. To determine the efficacy of hypertonic saline in dextran solution (HSD, 7.5% NaCl in 6% dextran 70) for the treatment of heat stroke, rats were deprived of water for 24 h (DE) or not (ND), and then they were heat-stressed, and 4 mL/kg of saline (SAL) or HSD was administered via jugular cannula at the end of heat stress (a core temperature of 42.

Cholinergic drug interactions and heat tolerance.

Acute, subchronic and chronic exposures to cholinergic compounds may result in differing effects. The efficacy of pyridostigmine bromide (PY) prophylaxis against organophosphorus poisoning depends on post exposure atropine (AT) administration. AT induces a dose-dependent increase in rate of rise of core temperature in heat exposed humans and rats.

Fluid shifts induced by the administration of 7.5% sodium chloride in 6% dextran 70 (HSD) in dehydrated swine.

This study determined the effects of HSD administration on fluid distribution, following dehydration in Female Yucatan micro pigs. Dehydration at 33 degrees C resulted in: significantly increased core temperature (37.2 +/- 0.

Ambient temperature effects on thermoregulation and endurance in anticholinesterase-treated rats.

In sedentary animals, physostigmine (PH) administration resulted in a decreased core temperature that is ambient temperature (Ta) dependent. PH administration in rats exercising on a treadmill (26 degrees C, 50% rh, 11m/min, 6 degrees incline) decremented endurance and increased rate of rise of core temperature (heating rate, HR). This study was undertaken to examine the effects of Ta on the endurance and thermoregulatory decrements of PH-treated running rats.

Physostigmine: dose-response effects on endurance and thermoregulation during exercise.

We previously reported that the administration of 200 micrograms/kg of physostigmine (PH) to rats exercising on a treadmill resulted in decrements in both endurance (decreased running time to exhaustion) and thermoregulation. However, it was necessary to determine the dose-response effects of PH administration before PH-treated exercising rats could be used as a model with which to examine the relative anticholinergic potency of drugs. In the present work saline, 50, 100, or 200 micrograms/kg of physostigmine salicylate (0%, 40%, 50%, and 60% whole blood cholinesterase inhibition) was administered to rats (N = 12/group) prior to treadmill exercise (26 degrees C, 50% rh, 11 m/min, 6 degrees incline).

Anticholinergics: effects on thermoregulation and performance in rats.

Atropine (AT) induces a dose-dependent increase in rate of rise of core temperature (heating rate) in sedentary heat-stressed rats, a muscarinic anticholinergic (MA) effect which is quantitatively similar to the increase in heating rate seen in heat-exposed men after equivalent atropine dose. In the heat-stressed rat, scopolamine (S) was found to have 16 x the MA effect of AT and, in the present study, aprophen (AP) and trihexyphenidyl (THP) manifested 0.067 x 0.

Spectrophotometric determination of circulating cholinesterases in rats.

A spectrophotometric assay was established to determine circulating levels of cholinesterase (ChE) in the whole blood of rats. A commercially available ChE reagent set was obtained and the suggested procedure modified to quantify and correct for the activity resulting from nonenzymatic hydrolysis of the substrate. The stability of ChE as well as the effect of sampling site, exercise, and carbamate administration were evaluated.

Chronic vs acute carbamate administration in exercising rats.

Physostigmine (PH), alone, and pyridostigmine (PY), in combination with atropine and 2-PAM, have been shown to protect animals against organophosphate poisoning. While acute administration of either of these carbamates increased heating rates and decreased endurance of exercising rats, chronically administered PY did not induce these decrements, and we hypothesized that chronic administration of PH could also result in similar attenuation of these effects. Thus, PH was administered acutely (iv) or chronically (osmotic mini-pump) in the following 4 groups (510-530g, male, N = 10/group): C (control, saline iv), AC-200 (acute, 200 ug/kg, 58% whole blood cholinesterase (ChE) inhibition), CH-7 (chronic, 125 ug/hr, 7 days, 60% inhib.

Atropine, diazepam, and physostigmine: thermoregulatory effects in the heat-stressed rat.

We have previously reported that administration of atropine (A) to unrestrained, sedentary, heat-stressed rats resulted in a dose-dependent increase in heating rate (rate of rise of core temperature, degree C/min). Additionally, we have demonstrated that the decrements in treadmill endurance and increments in heating rate of physostigmine (PH)-treated running rats can both be restored to control levels by pretreating the animals with A and diazepam (D). Our objective in the present work was to determine if the administration of D + PH to A-treated unrestrained, sedentary, heat-stressed rats (N = 16/group, 510-530 g) could improve their thermal tolerance.

Intramuscular and intravenous atropine: comparison of effects in the heat-stressed rat.

In our rat model of human heat injury we have administered atropine intravenously (iv); for clinical use in man, administration is by either the intramuscular (im) or iv route. In order to determine potential differences due to route of administration, we compared the dose-response effects of im and iv administration in rats. Adult male rats (500 g) were heat-stressed (41.

Carbamates, atropine, and diazepam: effects on performance in the running rat.

We have reported that when rats (500 g, male) are exercised to exhaustion on a treadmill, pretreatment with the centrally acting carbamate physostigmine reduced endurance (run time, RT) and increased the rate of rise of core temperature (Tc+). Both RT and Tc+ were restored to control levels by pretreatment with either or a combination of atropine (A), and diazepam (D). Our objective in the present work was to determine whether A+D could also restore the performance and thermoregulatory decrements induced by the peripherally acting carbamate pyridostigmine (PY).

Carbamate-induced performance and thermoregulatory decrements restored with diazepam and atropine.

When rats (500 g, male) are exercised on a treadmill, pretreatment with the carbamate physostigmine reduces endurance capacity (run time, RT) and increases the rate of rise of core temperature (heating rate, HR). Because physostigmine is a potential nerve agent pretreatment drug, our objective was to determine whether pharmacological intervention could reverse these decrements in performance and thermoregulation. The following drugs were administered separately via tail vein: vehicle-control (C), atropine (200 micrograms.

Novel approaches to the pathophysiology of heatstroke: the energy depletion model.

De-emphasis of the role of anhydrosis as the primary cause of heatstroke has resulted in increased usage and acceptance of animal models for heatstroke research. When the total amount of work achieved by the running rat prior to exhaustion was plotted against the rate of heat storage, a heretofore unrecognized relationship emerged. These new data suggest that physical exhaustion and heat exhaustion represent opposite ends of a continuum related to the rate of heat storage.

A heat-stressed rat model to determine relative anticholinergic and anticholinesterase drug potency.

We have reported that atropine, the prototype of muscarinic anticholinergic drugs, elicits a dose-dependent increase in core temperature of heat-stressed rats. In the present study, we have quantified the effects of other anticholinergic drugs on increments in core temperature and have derived the following potencies relative to atropine: imipramine 0.004, amitriptyline 0.

An atropinized heat-stressed rat model: dose response effects and pharmacokinetics.

Atropine and other anticholinergic drugs are widely used in common medications and in the treatment of organophosphate poisoning. Man dissipates heat by the evaporation of sweat. Analogously, rats spread saliva over their bodies for evaporative cooling.