Hyperthermic Rats Research Articles

Brain temperature modifies glutamate neurotoxicity in vivo.

The purpose of this study was to examine the effects of mild hypothermia and hyperthermia on glutamate excitotoxicity. Glutamate-induced cortical lesions were produced in hypothermic (32 degrees C), normothermic (37 degrees C), and hyperthermic (40 degrees C) rats by perfusion of a 0.5 M glutamate solution via a microdialysis probe. The volume of the lesion 7 days after glutamate perfusion was quantified histologically by image analysis. This histological assessment was performed in two experiments; in one, each of the target temperatures was induced before glutamate perfusion, and in the other, each of the target temperatures was induced after stopping the glutamate perfusion. We also examined the effect of temperature on the diffusion of exogenously delivered material in the extracellular space using autoradiography of the perfused glutamate solution containing 14C-labeled sucrose. In the two experiments in which each of the target temperatures was induced before or after glutamate perfusion, the volume of damage was reduced by mild hypothermia and enlarged by mild hyperthermia. The volume of 14C diffusion also increased as brain temperature increased. These results provide evidence that small variations of brain temperature modify glutamate excitotoxicity. The results also suggest that the change in glutamate diffusion in the extracellular space is one mechanism by which mild hypothermia and hyperthermia exert their protective and harmful effects respectively.

Behavioral approach to the study of the upper limit of temperature tolerance in rats

Caputa, M., K. Dokładny and B. Kurowicka. Behavioral approach to the study of the upper limit of temperature tolerance in rats. PHYSIOL BEHAV 65(1) 183–189, 1998.—A simple test of critical thermal maximum (CTM) to assess a break-down of heat-escape behavior in rats is described. Experiments were performed on 18 unrestrained adult Wistar rats of both sexes. Hypothalamic and intraperitoneal (i.p.) temperatures as well as motor activity were simultaneously and continuously recorded in the rats exposed to heat. When animals were growing restless, as evidenced by an increase in their motor activity, which was usually recorded at hypothalamic temperatures well above 41°C, we started testing CTM. To assess heat-escape behavior we used a precooled cooling bar (a part of a camp-cooler) which was placed at intervals in a climatic chamber. The hyperthermic rats, given the bar for 30 s, mounted it vigorously until they failed at particular levels of brain and body temperatures which were recognized as respective CTM values. Rapid external cooling of rats prevented lethal effects of the heat exposure. We were able to show effects of timing of heat exposure on heat tolerance. We also managed to detect small but significant differences in heat tolerance of warm-reared (an increase), cold-reared (a decrease), and bacterial–endotoxin-treated (an increase) rats. The heat-escape behavior was less heat-resistant than selective brain cooling response which was still present at CTM point. In conclusion, our CTM test is a safe and reliable way to study heat tolerance in rats.

Analgesic and antipyretic properties ofEuphorbia royleanalatex

The ethyl acetate fraction (EA) from the residue of an 85% ethanol extract of the latex of Euphorbia royleana (Euphorbiaceae) was investigated for antipyretic and analgesic properties. The results showed a dose related peripheral analgesic effect. The fraction assayed exhibited a significant antipyretic effect in hyperthermic rats and rabbits. The oral LD50 was more than 2 g/kg in rats and mice. © 1997 John Wiley & Sons, Ltd.

Administration of fenfluramine at different ambient temperatures produces different core temperature and 5-HT neurotoxicity profiles

This study investigated the effect of two different ambient temperatures on fenfluramine-induced 5-HT neurotoxicity. Fenfluramine (FEN) (12.5 mg/kg×4; injections made hourly) or saline (SAL) was administered to rats in either a normal laboratory temperature of 24°C or a warm environment of 30°C. Animals were kept at that ambient temperature for 20 h after FEN administration. Ambient temperature was controlled to ±0.5°C and rat core temperature was continually measured using a non-invasive apparatus. FEN-treated rats at 24°C displayed a core temperature hypothermia with a peak low of 33.8°C, and this core temperature hypothermia lasted for 20 h after FEN administration. Rats treated with FEN at 30°C displayed a significant core temperature hyperthermia for 4 h after the first drug injection compared to SAL-treated groups, with a peak core temperature of 38.6°C. 2 weeks after FEN injections, brain regions were analyzed by HPLC. Both groups of FEN-treated rats showed decreases in 5-HT and 5-HIAA in the hippocampus, frontal cortex, somatosensory cortex, striatum, hypothalamus and septum. However, FEN rats treated at 30°C had significantly greater decreases (26–35%) in 5-HT compared to FEN-treated rats at 24°C in the frontal cortex, hippocampus, striatum and somatosensory cortex and significantly greater decreases (26–50%) in 5-HIAA in the frontal cortex, hippocampus and somatosensory cortex. This study indicates fenfluramine can produce neurotoxicity in rats that display either a core temperature hypothermia or hyperthermia, although hyperthermic rats have greater 5-HT and 5-HIAA depletions than the hypothermic rats.

Selective Expression of HSP70-1 Gene in the Adrenal Cortex but Not in the Medulla of Thermally Stressed Rats

The heat shock protein 70 (HSP70) gene expression in rat adrenal glands was investigated.In situhybridization and Northern blotting revealed a marked increase of inducible HSP70 (HSP70-1) gene expression in the adrenal cortex, but not in the medulla, after whole body hyperthermia.In vivofootprinting assay of HSP70-1 promoter region suggested a possible involvement of other factor(s) in addition to the heat shock factor (HSF). We also detected significant increases of both ACTH and corticosterone in the plasma of the hyperthermic rats. These results suggested some physiological factors other than HSF may also participate in the tissue-specific induction of HSP70-1 genein vivo.

Delayed postischemic hyperthermia in awake rats worsens the histopathological outcome of transient focal cerebral ischemia.

Over the past several years, it has been demonstrated that mild intraischemic or immediate postischemic hyperthermia worsens ischemic outcome in models of global and focal ischemia. Periods of hyperthermia are commonly seen in patients after stroke and cardiac arrest. The hypothesis tested in this study was that a brief hyperthermic period, even when occurring days after an ischemic insult, has detrimental effects on the pathological outcome of focal ischemia. Rats were subjected to 60 minutes of transient middle cerebral artery occlusion by insertion of an intraluminal filament. Twenty-four hours after reperfusion, awake rats were subjected to temperature modulation for 3 hours in a heating chamber. The brain temperature was equilibrated to either 37 degrees C to 38 degrees C, or 40 degrees C. Changes in rectal temperature and blood glucose concentration were evaluated during and just after temperature modulation. Behavioral tests were also assessed. Three days after temperature modulation, brains were perfusion-fixed, and infarct volumes were determined. In animals with 40 degrees C hyperthermia, cortical and total infarct volumes were markedly greater (92.2 +/- 63.1 and 126.5 +/- 72.3 mm3 [mean +/- SD], respectively) than in normothermic rats (14.4 +/- 12.7 and 42.4 +/- 19.2 mm3) and in animals with 39 degrees C hyperthermia (16.5 +/- 28.7 and 40.9 +/- 34.3 mm3) (P < .05), whereas there was no significant difference between normothermic and 39 degrees C hyperthermic animals. In addition, animals with 40 degrees C hyperthermia displayed worsened neurological scores compared with normothermic and 39 degrees C hyperthermic rats. In the 39 degrees C hyperthermia group, rectal temperatures were significantly lower (by 0.2 degree C to 0.5 degree C) than brain temperatures throughout the modulation period. The present findings provide evidence that, after a transient focal ischemic insult, the postischemic brain becomes abnormally sensitive to the effects of delayed temperature elevation, even of moderate degree. The threshold for aggravation of ischemic injury by delayed hyperthermia appears to be approximately 40 degrees C. Body-temperature measurements, in both awake and anesthetized animals, may not accurately reflect brain temperature under these conditions. The present study stresses that fever of even moderate degree in the days following brain ischemia may markedly exacerbate brain injury.

Heat-induced acute hyperthermia results in a reversible depression of cold defence in the rat ( Rattus norvegicus)

1. 1. Adult female Wistar rats were made hyperthermic (colonic temperature, T c, of 41 to 42°C for 60 min) by external heating and then tested for their autonomic cold defence (cold exposure of 15°C for 45 min) either immediately after hyperthermia or 2 h later. 2. 2. Compared with cold defence of normothermic controls, hyperthermic rats showed a decreased cold-induced thermogenesis and a fall in the body temperature threshold for its elicitation, both resulting in a greater reduction in T c. 3. 3. Two to three days after hyperthermia all measured parameters of cold defence returned to the normal values observed before hyperthermia. 4. 4. The reversible depression of cold defence demonstrated by the present study can be interpreted as a sign of adaptive modification in thermoregulation, probably helping recovery from hyperthermia.

Body temperature effect on methylenedioxymethamphetamine-induced acute decrease in tryptophan hydroxylase activity

Brain tryptophan hydroxylase activity decreases within 15 min after a single administration of 3,4-methylenedioxymethamphetamine. In the present study, the effect of body temperature on this acute decrease of tryptophan hydroxylase activity was examined. 2 h after a single dose of 3,4-methylenedioxymethamphetamine (20 mg/kg, s.c.), rats exhibited hyperthermia (38.7°C) or hypothermia (35.8°C) when maintained at 25°C or 6°C, respectively. The rectal temperature of control animals maintained at 6°C was not altered. Tryptophan hydroxylase activity measured in the hippocampus, striatum and frontal cortex of hyperthermic rats treated with 3,4-methylenedioxymethamphetamine was decreased to 61%, 65% and 71% of control levels, respectively, 2 h after drug treatment. However, in hypothermic rats, 3,4-methylenedioxymethamphetamine had no effect on tryptophan hydroxylase activity in the hippocampus, striatum or frontal cortex. Non-drug-induced hyperthermia or hypothermia did not affect tryptophan hydroxylase activity. Since hypothermia may prevent the 3,4-methylenedioxymethamphetamine-induced decrease in tryptophan hydroxylase activity by reducing the formation of free radicals, the effect of a free radical scavenging agent, N-tert-butyl-α-phenylnitrone, was examined. N-tert-butyl-α-phenylnitrone (200 mg/kg, i.p.) alone caused hypothermia but had no direct effect on tryptophan hydroxylase activity. Preadministration of N-tert-butyl-α-phenylnitrone prevented 3,4-methylenedioxymethamphetamine from raising the temperature above normal and attenuated the drug-induced decrease in tryptophan hydroxylase activity in hippocampus, striatum and frontal cortex. However, when the rats treated with a combination of N-tert-butyl-α-phenylnitrone and 3,4-methylenedioxymethamphetamine were maintained at hyperthermic conditions, N-tert-butyl-α-phenylnitrone had no protective effect. These results suggest that body temperature plays a prominent role in the 3,4-methylenedioxymethamphetamine-induced acute decrease in tryptophan hydroxylase activity.

Body temperature effect on methylenedioxymethamphetamine-induced acute decrease in tryptophan hydroxylase activity

Brain tryptophan hydroxylase activity decreases within 15 min after a single administration of 3,4-methylenedioxymethamphetamine. In the present study, the effect of body temperature on this acute decrease of tryptophan hydroxylase activity was examined. 2 h after a single dose of 3,4-methylenedioxymethamphetamine (20 mg/kg, s.c.), rats exhibited hyperthermia (38.7°C) or hypothermia (35.8°C) when maintained at 25°C or 6°C, respectively. The rectal temperature of control animals maintained at 6°C was not altered. Tryptophan hydroxylase activity measured in the hippocampus, striatum and frontal cortex of hyperthermic rats treated with 3,4-methylenedioxymethamphetamine was decreased to 61%, 65% and 71% of control levels, respectively, 2 h after drug treatment. However, in hypothermic rats, 3,4-methylenedioxymethamphetamine had no effect on tryptophan hydroxylase activity in the hippocampus, striatum or frontal cortex. Non-drug-induced hyperthermia or hypothermia did not affect tryptophan hydroxylase activity. Since hypothermia may prevent the 3,4-methylenedioxymethamphetamine-induced decrease in tryptophan hydroxylase activity by reducing the formation of free radicals, the effect of a free radical scavenging agent, N-tert-butyl-α-phenylnitrone, was examined. N-tert-butyl-α-phenylnitrone (200 mg/kg, i.p.) alone caused hypothermia but had no direct effect on tryptophan hydroxylase activity. Preadministration of N-tert-butyl-α-phenylnitrone prevented 3,4-methylenedioxymethamphetamine from raising the temperature above normal and attenuated the drug-induced decrease in tryptophan hydroxylase activity in hippocampus, striatum and frontal cortex. However, when the rats treated with a combination of N-tert-butyl-α-phenylnitrone and 3,4-methylenedioxymethamphetamine were maintained at hyperthermic conditions, N-tert-butyl-α-phenylnitrone had no protective effect. These results suggest that body temperature plays a prominent role in the 3,4-methylenedioxymethamphetamine-induced acute decrease in tryptophan hydroxylase activity.

Influence of acute exposure to heat on the blood-brain barrier permeability during acute hypertension

In mild hyperthermic rats with acute hypertension induced by intravenous injection of adrenaline, changes in blood-brain barrier permeability to macromolecules were investigated using Evans blue as indicator. Evans blue albumin extravasation was determined macroscopically, and a quantitative estimation with spectrophotometer using homogenized brain to release the dye was also performed to evaluate the macroscopic findings. Four groups of rats were studied: group I: control normothermia; group II: acute exposure to heat; group III: normothermia + acute hypertension; group IV: acute exposure to heat + acute hypertension. The rats were anesthetized with diethyl-ether. Body temperature was increased by elevating ambient temperature in the vented box covered with a 3 mm thick black copper plate. The colonie temperature was increased to 39 ± 0.5 °C. During adrenaline-induced acute hypertension the mean arterial blood pressure increased in both normothermic and mild hyperthermic animals. Mean values for Evans blue dye were found to be 0.20 ± 0.04 mg% whole brain in normothermic control rats and 0.30 ± 0.1 mg% in hyperthermic rats (p < 0.05). Mean values for Evans blue dye in the whole brain were found to be 0.63 ± 0.2 mg% in the normothermic rats and 0.40 ± 0.2 mg% in the mild hyperthermic rats during adrenaline-induced hypertension (p < 0.05). Our results show that the extravasation of Evans blue albumin was less pronounced in the brains of mild hyperthermic rats compared to normothermic rats after adrenaline-induced acute hypertension.

The influence of body temperature on infarct volume and thrombolytic therapy in a rat embolic stroke model

The effect of body temperature on cerebral infarcts and thrombolytic therapy was investigated in 91 rats embolized in the right carotid territory. Hypothermia of 32°C for 2 h with preembolic onset ( n = 15) or hyperthermia of 39°C for 2 h with postembolic onset ( n = 22) was compared to normothermic controls ( n = 17). After 48 h of survival, neuropathological evaluation with measurement of infarct volume was performed. Median infarct volume in percent of affected himisphere volume was 11% (9–21, quartiles) in rats treated with hypothermia alone, compared to 46% (14–59, quartiles) in normothermic controls ( P = 0.04). Hyperthermia for 2 h increased median infarct volume to 65% (37–75, quartiles). There was a positive and significant correlation between infarct volume and body temperature ( R = 0.53, P = 0.0002, n = 54). Mortality rate was significantly higher among rats treated with hyperthermia compared to normothermic controls ( P = 0.005). A subset of 37 rats exposed to the same temperature regimen were treated with tissue plasminogen activator (20 mg/kg i.v. during 45 min) 2 h after embolization. Judged by posttreatment carotid angiography, hyperthermic rats ( n = 11) had the best degree of recanalization ( P = 0.03) compared to controls ( n = 17), but median infarct volume in this group was (58% (27–67, quartiles)) significantly larger ( P < 0.02) than normothermic (21% (15–39, quartiles), n = 14) and hypothermic (13% (7–31, quartiles)), n = 12) rats treated with thrombolytic therapy. Thrombolytic therapy following 2 h of hypothermia, could not improve the effect of hypothermia alone. We conclude, that the size of infarcts in our embolic stroke model is dependent on the body temperature during the initial phase of infarct development. Hyperthermia had a detrimental effect when combined with thrombolytic therapy and should be avoided in clinical trials of this treatment.

Changes of labile metabolites during anoxia in moderately hypo- and hyperthermic rats: correlation to membrane fluxes of K+

The objective of this study was to assess the influence of temperature on the coupling among energy failure, depolarization, and ionic fluxes during anoxia. To that end, we induced anoxia by cardiac arrest in anesthetized rats maintained at a body temperature of either 34°C or 40°C, measured extracellular K+ concentration (Ke+), and froze the neocortex through the exposed dura for measurements of phosphocreatine (PCr), creatine (Cr), ATP, ADP, and AMP, glucose, glycogen, pyruvate and lactate content after ischemic intervals of maximally 130 s. Free ADP (ADPf) concentrations were derived from the creatine kinase equilibrium. Hypothermia reduced the initial rate of rise in Ke+, and delayed the terminal depolarization; however, both hypo- and hyperthermic animals showed massive loss of ion homeostatis at a Ke+ of 10–15 mM. The initial rate of rise in Ke+ did not correlate to changes in ATP, or ATP/ADPf ratio, suggesting that temperature changes per se may control the degree of activation of K+ conductances. The results clearly showed that, in both hyper- and hypothermic subjects, energy failure preceded the sudden activation of membrane conductances for ions. The results indicate that temperature primarily influences membrane permeability to ions like Ke+ (and Na+), and that cerebral energy state is secondarily affected. It is proposed that the higher rate of rise of Ke+ at high temperatures accelerates ATP hydrolysis primarily by enhancing metabolic rate in glial cells.

Exercise performance of normothermic and hyperthermic rats: Effect of warm rearing

1. 1.|Hypothalamic and rectal temperatures were recorded in 8 warm-reared (wr) and 12 control rats. Rats ran to exhaustion at a constant speed of 1.5 km h −1 but at a variable ambient temperature adjusted to stabilize their hypothalamic temperature at 38.0°C (normothermia) or 41.0°C (hyperthermia). Blood lactate concentrations were determined before and after exercise. 2. 2.|Exercise caused exhaustion in normothermic control rats after 62.08 ± 5.43 min and in wr rats after 29.64 ± 2.09 min. 3. 3.|Hyperthermia shortened to one half (to 12.24 ± 1.36 min) and to one fourth (to 16.15 ± 1.20 min) the endurance time in wr and control rats, respectively. 4. 4.|There were no correlations between lactate concentraion and hyperthermia or endurance time. 5. 5.|In conclusion, in rats and other animals which have safe refuges, hyperthermia interferes with the ability to continue exercising.

Interrelationships between increased vascular permeability and acute neuronal damage following temperature-controlled brain ischemia in rats

This study examined regional patterns of increased vascular permeability and morphological indicators of acute neuronal injury following normothermic and mildly hyperthermic forebrain ischemia. Rats underwent 20 min of four-vessel occlusion during which intraischemic brain temperature was maintained at either 37 degrees C or 39 degrees C. At 45-min recirculation, the blood-brain barrier (BBB)-tracer horseradish peroxidase was injected and rats were perfusion-fixed at 1-h recirculation for light and electron microscopic analysis. In normothermic and hyperthermic rats, sites of increased vascular permeability were spatially correlated with dark shrunken type IV neurons. Neuronal alterations within cortical, hippocampal, striatal, and thalamic areas ranged from mild cytoplasmic vacuolation and mitochondrial swelling to severe cytoplasmic shrinkage and increased density. Although dark shrunken neurons were routinely associated with permeable blood vessels in both temperature groups, dark neurons were not detected in regions demonstrating an intact BBB. Following normothermic brain ischemia, the appearance of dark shrunken neurons was restricted to the cerebral cortex and striatum. In both temperature groups, luminal leukocytes were detected within otherwise well-perfused forebrain microvascular beds. Our studies suggest a close interrelationship between postischemic microvascular abnormalities, including increased vascular permeability, and morphological indicators of acute neuronal injury following brain ischemia.

Do changes in body temperature following envenomation by the scorpion Leiurus quinquestriatus influence the course of toxicity?

M. Ismail, M. A. Abd-Elsalam and A. M. Morad. Do changes in body temperature following envenomation by the scorpion Leiurus quinquestriatus influence the course of toxicity? Toxicon 28, 1265–1284, 1990.—Four fatal cases following scorpion sting in children are presented. Two victims had rectal temperature above 41°C, the third exhibited a temperature of 40.9°C from the combined effects of scorpion sting and heat stroke, while the fourth was hypothermic. All victims developed hypothermia 48 hr following the sting. The hyperthermia was effectively treated by acetaminophen suppositories, ice packs and water sponges. All victims showed late hypotension that was refractory to dopamine infusion. This was explained by bradykinin released by the venom blocking the dopaminergic receptors. Deterioration of the cortical activity of the victims maintained on mechanical ventilation before the incidence of asystole suggests a central component in the cardiovascular manifestations of envenomation. A. amoreuxi venom was selected as a model for the pharmacokinetic and quantitative toxicological studies since it has no effect on body temperature. In hyperthermic rabbits injected with labelled lethal fraction of A. amoreuxi venom, there was a significant decrease in the elimination half-life, t 1 2 β , the apparent volume of the tissue compartment, V t, the apparent volume of distribution, V dss, and the intercompartmental rate constant, k CT. Hypothermic rabbits showed a significant decrease in the apparent first-order elimination rate constant, k d, and a significant increase in the elimination half-life. In both states a higher concentration of the lethal fraction in the blood was calculated. This would explain the rapidity of onset of the electrocardiographic effects and the decreased survival time in both the hyperthermic and hypothermic rabbits injected with venom when compared to normothermic animals. The s.c. ld 50 in mice and the i.v. MLD in rats were significantly reduced in the hypothermic mice and hypothermic and hyperthermic rats.

In vitro evidence for modification of rat liver glucocorticoid receptor binding properties and transformation by hyperthermia

The physico-chemical parameters of the interaction of [ 3H]triamcinolone acetonide (TA) with the glucocorticoid receptor (GR) and the in vitro activation of glucocorticoid-receptor complexes were studied in liver cytosols of rats exposed to 41°C hyperthermia. A significant reduction in glucocorticoid binding and a slight increase in binding affinity were detected in hyperthermic rats as compared to the controls. The number of binding sites was 0.48 ± 0.02 and 0.73 ± 0.03 pmol/mg protein for heat-treated and control rats, respectively. Differences in equilibrium dissociation constants (0.52 ± 0.08 nM for hyperthermic and 0.94 ±0.13 nM for control animals) were reflected in corresponding differences in dissociation rate constants at 25°C (5.1 × 10[su−4] and 7.5 × 10 −4min −1, respectively), whereas association rate constants were similar. The inactivation kinetics of unoccupied GR at 25°C was the same in both groups. Glucocorticoid-receptor complexes in liver cytosol from hyperthermic and control rats were thermally activated to a similar extent, but the activation rate was significantly lower in the former. Mixing experiments with the control and hyperthermic rat liver cytosols suggest that this impairment of glucocorticoid-receptor complexes activation could be at least in part ascribed to heat stress-related changes in the action of activation modulator(s). Sedimentation behaviour of unactivated and activated [ 3H]TA-receptor complexes of hyperthermic and control rats was identical.

Changes in blood volume and vascular compliance during body heating in rats

The effects of hyperthermia on blood volume and effective vascular compliance were studied in control and heat acclimated rats (three weeks at 32 degrees C and 50% R.H.). Experiments were performed on conscious rats whose abdominal aorta and both jugular veins were cannulated. Continuous changes in blood volume (BV) were monitored by measuring 51Cr tagged erythrocyte dilution, using an arterio-venous extracorporeal shunt passing through a gamma counter. Total vascular compliance was calculated from the relation between changes in BV and central venous pressure during 10 min of infusion of saline at a rate of 1.6% body wt/10 min. Hyperthermia induced a significant blood volume expansion. This expansion was more pronounced in non-acclimated rats. Effective vascular compliance was similar in the normothermic, both non-acclimated and acclimated rats. However, while hyperthermia did not affect the vascular compliance of non-acclimated rats, it was decreased significantly in the acclimated hyperthermic rats. The data suggest that changes in vascular compliance play a role when rapid blood volume changes take place, especially in acclimated hyperthermic animals. The relations between changes in vascular compliance and heat induced redistribution of cardiac output are discussed.

Increase in rat intestinal permeability to endotoxin during hyperthermia.

Victims of heat stroke exhibit several clinical features which are also encountered in endotoxaemia. In order to investigate these similarities hyperthermic rats were used to explore the possibility that high body temperature results in increased permeability of intestinal wall to endotoxin. 125I endotoxin was introduced into intestinal segments taken from non-heat exposed rats. The segments were then incubated at 37 degrees C or 45 degrees C. Intestinal segments from heat stressed rats were similarly prepared and incubated at 37 degrees C. Leakage of endotoxin from segments taken from heat stressed rats was three times greater than from those from non-heat stressed rats, as were the segments from non-heat stressed rats which were incubated at 45 degrees C. These results indicate that the intestinal membrane is damaged by heat and that an increase in outward leakage of microbial endotoxins from the gut then occurs. This might contribute to the pathophysiological picture of heatstroke.

Synthesis of heat shock proteins in rat brain cortex after transient ischemia.

Cell-free protein synthesis and two-dimensional gel autoradiography were used to characterize early postischemic protein synthesis in rat neocortex. Severe forebrain ischemia was induced for 30 min (four-vessel occlusion model) and followed by 3 h of recirculation. Polysomes were isolated from the cerebral cortex, translated in vitro in a reticulocyte system, and analyzed by two-dimensional gel electrophoresis. The translation products of postischemic polysomes included a major new protein family (70 kDa) with multiple isoelectric variants that was found to comigrate with the 68- to 70-kDa "heat shock" protein synthesized from polysomes of hyperthermic rats. Two other stress proteins (93 and 110 kDa) also appeared to be synthesized in increased amounts after ischemia. A complement of proteins that was indistinguishable from that of controls was also synthesized after ischemia, indicating that messenger ribonucleic acid coding for most brain proteins is preserved after ischemia and is bound to polysomes.

Surfactant deficiency in rats without a decreased amount of extracellular surfactant.

Low volume ventilation without periodic large inflations leads to diminished alveolar stability and to the accumulation of increased amounts of airway disaturated phosphatidylcholine (DSPC) in large aggregates that sediment at 1,000 g; surfactant in this form lowers surface tension less rapidly than surfactant present in the 1,000-g supernatant fraction. These observations led to the present work in which we tested the notion that alveolar instability may develop in the presence of an undiminished quantity of total airway surfactant, if the amount of surfactant found in the 1,000-g supernatant fraction is diminished. Pulmonary compliance fell and the alveolar-arterial O2 gradient widened in normothermic rats during constant ventilation in the resting tidal volume range, and, in hyperthermic rats (approximately 39 degrees C) similarly ventilated but with the addition of periodic sighs. The total amount of airway DSPC was undiminished in each group, but in each less DSPC was present in the 1,000-g supernatant fraction compared with controls. Alveolar instability and hypoxemia also developed in hyperthermic rats during low volume ventilation without periodic sighs. Although the total amount of airway DSPC was decreased in these rats, enough remained to theoretically form a continuous monomolecular film over the entire alveolar surface at functional residual capacity; however, there was insufficient surfactant in the 1,000-g supernatant fraction to form such a continuous film. These findings demonstrate that the mode of ventilation, and moderate hyperthermia, may lead to decreased alveolar stability despite the presence of normal amounts of airway surfactant, and, by inference, indicate the extracellular form or state of surfactant has an important effect on alveolar stability.