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Genetic selection of rats with high and low body temperatures.

Body (core) temperature (T(c)) directly affects all biological processes, including sensitivity to toxic chemicals, development, aging, and drug metabolism. To understand how T(c) affects these processes it is necessary to alter T(c) independently of other physiological processes. The purpose of this study was to determine whether selective breeding techniques can be used to develop lines of rats with hyperthermic and hypothermic T(c)'s. T(c) and motor activity of 24 female and 23 male rats (parental line) of the NIH heterogenous stock were monitored by telemetry for 96h at a T(a) of 22 degrees C. The mean 24h T(c) of the male and female rats was 37.3 degrees C with a range of 37-38.2 degrees C. T(c) was not correlated with motor activity or body weight. Pairs with the lowest and highest T(c)'s were selected for breeding. The F1 generation consisted of 10 offspring from the hyperthermic group and 20 from the hypothermic group. They were implanted with transmitters at 60d of age. T(c) of rats derived from the hyperthermic parental line had a significantly warmer T(c) than the rats derived from the hypothermic parental line. Motor activity was significantly higher in the hyperthermic F1 males and hypothermic F1 females. Breeding of hyperthermic and hypothermic rats has shown that adult offspring of the fourth generation maintain significantly different core temperatures but have similar patterns of motor activity. The results demonstrate that T(c) is heritable and that it should be feasible to develop lines of rats that regulate T(c) above or below normal.

Journal Article↗

PISA. The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690].

BACKGROUND: During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily) and low dose (3 g daily) paracetamol (acetaminophen) in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4 degrees C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied. AIM: The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments. DESIGN: Seventy-five (3 x 25) patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out.

Acetaminophen↗

Effects of intracranial injections of 6-OHDA on food and water intakes, body temperature and body weight regulation in the rat.

6-Hydroxydopamine was injected either intraventricularly (320 mug in 10 mul) or intrahypothalamically (64 mug in 2 mul) into rats kept under either free feeding or body weight reduced conditions. Intraventricular injections caused a temporary aphagia and hypodipsia in free feeding rats but daily measurements failed to reveal any long term effects; body weight reduced rats did not display the temporary aphagia but were initially hyperphagic. Injections into the more rostral hypothalamic areas of free feeding rats also showed only minimal short term effects; however, some of the body weight in both body weight reduced group died within several days of injection. Injections made at more posterior loci again showed very little effect in both body weight reduced and free feeding groups; some temporary disruption of feeding occurred from lesions in the proximity of the zone incerta of some free feeding animals.

Animals↗

Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage.

OBJECTIVES: To assess the frequency of hyperthermia in a population of acute neurosurgical patients; to assess the relation between brain temperature (ICT) and core temperature (Tc); to investigate the effect of changes in brain temperature on intracranial pressure (ICP). METHODS: The study involved 20 patients (10 severe head injury, eight subarachnoid haemorrhage, two neoplasms) with median Glasgow coma score (GCS) 6. ICP and ICT were monitored by an intraventricular catheter coupled with a thermistor. Internal Tc was measured in the pulmonary artery by a Swan-Ganz catheter. RESULTS: Mean ICT was 38.4 (SD 0.8) and mean Tc 38.1 (SD 0.8) degrees C; 73% of ICT and 57.5% of Tc measurements were > or =38 degrees C. The mean difference between ICT and Tc was 0.3 (SD 0.3) degrees C (range -0.7 to 2.3 degrees C) (p=0. 0001). Only in 12% of patients was Tc higher than ICT. The main reason for the differences between ICT and Tc was body core temperature: the difference between ICT and Tc increased significantly with body core temperature and fell significantly when this was lowered. The mean gradient between ICT and Tc was 0.16 (SD 0.31) degrees C before febrile episodes (ICT being higher than Tc), and 0.41 (SD 0.38) degrees C at the febrile peak (p<0.05). When changes in temperature were considered, ICT had a profound influence on ICP. Increases in ICT were associated with a significant rise in ICP, from 14.9 (SD 7.9) to 22 (SD 10.4) mm Hg (p<0.05). As the fever ebbed there was a significant decrease in ICP, from 17.5 (SD 8.62) to 16 (SD 7.76) mm Hg (p=0.02). CONCLUSIONS: Fever is extremely frequent during acute cerebral damage and ICT is significantly higher than Tc. Moreover, Tc may underestimate ICT during the phases when temperature has the most impact on the intracranial system because of the close association between increases in ICT and ICP.

Adult↗

Body temperature and ethanol pharmacokinetics in temperature-challenged mice.

The relationships between ambient temperature, body temperature, ethanol pharmacokinetics and behavioral sensitivity to ethanol were examined in C57BL/6 mice. Mice were injected intraperitoneally with 3.6 or 2.0 g/kg ethanol. Exposure to increasing ambient temperatures of 4-34 degrees C immediately after ethanol injection resulted in a significant increase in body temperature, ethanol elimination rate and brain:blood ethanol concentration ratios in 3.6 g/kg ethanol-injected mice, but not in mice injected with 2.0 g/kg ethanol. As the mean body temperature increased from 26.0 to 38.2 degrees C in the 3.6 g/kg mice, there was a 50% increase in ethanol elimination rate. Delayed (30 min) exposure to increasing ambient temperatures following injection of 3.6 g/kg ethanol resulted in a significant increase in ethanol elimination rate, a marked increase in the duration of loss of righting reflex and a decrease in ethanol concentration at the regain of righting reflex. The results indicate that temperature-induced changes in the absorption, distribution and elimination of ethanol do not appear to mediate the effects of temperature on behavioral sensitivity to ethanol in C57 mice.

Animals↗

Rhythms of temperature selection and body temperature are out of phase in the golden hamster.

Body temperature, locomotor activity, and thermoregulatory behavior of freely moving golden hamsters maintained in a spatial thermocline were measured over several weeks. The thermoregulatory behavior of temperature selection exhibited a robust daily rhythm 180 degrees out of phase with the rhythms of body temperature and locomotor activity. However, the parameters of the body temperature rhythm (rhythmicity, mean level, and amplitude) were not significantly affected by the thermoregulatory behavior. Although the observed phase difference between the rhythms of temperature selection and body temperature might suggest that thermoregulatory behavior is modulated to oppose (rather than to defend) the rhythm of body temperature, the absence of effect of temperature selection on the parameters of the body temperature rhythm fails to reveal the physiological significance of such opposition. Further studies are necessary to establish the physiological significance of the rhythm of temperature selection.

Animals↗

Effects of irrigation fluid temperature on core body temperature during transurethral resection of the prostate.

OBJECTIVES: To determine the effect irrigation fluid temperature has on core body temperature changes in patients undergoing transurethral resection of the prostate (TURP). METHODS: Fifty-six male patients (mean age 71.2 +/- 8.2 years) scheduled for TURP were enrolled in the study. Patients were randomized to one of two groups. Group 1 consisted of 27 patients who received room temperature irrigation fluid (70 degrees F) throughout TURP; group 2 consisted of 29 patients whose procedure was performed with warmed irrigation fluid (91.5 degrees F). The irrigation fluid used for both groups was glycine. The baseline temperature, final temperature, total time in the operating room, and amount of irrigation fluid used during the procedure were recorded for each patient. RESULTS: No significant difference in the average time spent in the operating room or in the total irrigation fluid used between the two groups was observed. Of the 27 patients who received room temperature irrigation fluid, 15 (55.6%) had a decrease in body temperature. A decrease in temperature was observed in 21 (72.4%) of the 29 patients who received warm irrigation fluid. Groups 1 and 2 had 12 (44.4%) of 27 and 8 (27.6%) of 29 patients, respectively, who demonstrated an elevation in their core body temperature. CONCLUSIONS: The results of our study suggest that irrigation fluid temperature is not a factor responsible for altering the core body temperature in patients undergoing TURP.

Aged↗

The effects of lactation and ambient temperature on the body temperature of female Norway rats.

Norway rat dams were placed in an ambient temperature of 4 degrees C, 22 degrees C, or 28 degrees C. Body temperatures were recorded over a two hour period on three days; each female was observed on Day 4 and Day 10 of lactation and three days after lactation was stopped. Body temperatures were initially higher during lactation than after lactation had stopped. Dams were less able to maintain their body temperatures in the 28 degrees C ambience on Day 4 of lactation than after lactation, and on Day 10 of lactation, were even less able to maintain their body temperatures than on Day 4. During lactation, dams were able to maintain and even increase their body temperatures in the 4 degrees C ambience. The data support the hypothesis that the acute hyperthermia encountered by rat dams during contact with their litters may be due to a physical restriction on maternal heat loss.

Animals↗

Prostaglandin fevers in rats: regulated change in body temperature or change in regulated body temperature?

Experiments examining the effects of central injections of E-series prostaglandins (PGE) on body temperature have only been done in the light part of a light-dark cycle. The present experiments examined the characteristics of fevers in rats after intraventricular PGE2 injections in both light and dark in a 12:12 h photoperiod. In the light, the change in body temperature (Tb) after 0.5 microgram was not significantly different from the change after vehicle injection. After injection of PGE2 (1, 2, 4, and 8 micrograms), Tb rose in a dose-dependent fashion. Mean initial Tb in the light was 36.4-36.6 degrees C. Tb rose a mean of 1.5 degrees C after 1 microgram, 1.9 degrees C after 2 micrograms, 2.7 degrees C after 4 micrograms, and 3.5 degrees C after 8 micrograms PGE2. A dose of 16 micrograms gave almost identical results as 8 micrograms. In the dark, mean initial Tb was 37.4-37.7 degrees C. Tb rose less than 0.8, 1.1, 1.4, and 2.3 degrees C after 1-8 micrograms PGE2, respectively. Thus there were two distinct dose-response curves for day and night. Nevertheless, peak Tb values attained in the two conditions were not significantly different from each other at any given dose. These results show that a particular dose of PGE2 raises Tb to a particular level, largely independent of either the Tb at the time of the injection or the phase of the light-dark cycle. However, the change in Tb at any dose depends strongly on initial Tb. Therefore, we urge researchers in the pharmacology of thermoregulation to report initial and final Tb values as well as changes in Tb.

Animals↗

Central versus peripheral effects on temperature preference and body temperature following alteration of 5-HT in maturing mice.

Experiments were designed to distinguish between central and peripheral effects on temperature preference and body temperature of drugs injected intraperitoneally (IP) in infant mice ranging in age from 3 to 10 days postpartum. These compared a drug restricted to the periphery ("peripheral" drug) with a drug of similar action that reaches the central nervous system (CNS) as well as the periphery. Two different classes of drugs were utilized to test central versus peripheral actions independently with drugs that have different modes of action: 1-aromatic amino acid inhibitors and serotonin receptor antagonists. Although the decarboxylase inhibitor NSD 1015, which reaches the central nervous system from IP injection, can significantly decrease temperature preference (Tpref), the peripheral inhibitor carbidopa had no significant effects on Tpref or on body temperature (Tb). Furthermore, pretreatment with NSD 1015 prevented the elevation of Tpref produced by the serotonin precursor 5-hydroxytryptophan (5-HTP); however carbidopa pretreatment had no effect on the increased Tpref produced by 5-HTP. In other experiments, the peripheral serotonin antagonist BW 501C was not able to prevent elevated Tpref produced by 5-HTP, although the specific 5-HT2 antagonist pirenperone, which reaches the CNS as well as the periphery, blocks the 5-HTP elevation of Tpref. Taking all of these results together, we conclude that the changes in Tb and Tpref following these treatments require a decarboxylase inhibitor or 5-HT antagonist that reaches the CNS. However, the well known and potent peripheral vasoconstrictor action of serotonin requires that peripheral effects of drugs be considered when manipulations are not restricted to the CNS.

5-Hydroxytryptophan↗

The impact of water temperature on core body temperature of North American river otters (Lutra canadensis) during simulated oil spill recovery washing protocols.

Ten North American river otters (Lutra canadensis) were anesthetized with Telazol and instrumented with ingestable radiotelemetry temperature sensors for measuring core body temperature. The otters were then subjected to a washing protocol to simulate rehabilitation following an oil spill contamination. This protocol consisted of a 30-min wash in a 1:16 dilution of dishwashing liquid using either cold (24 degrees C) water or water near baseline core body temperature (38.4 degrees C), followed by a 30-min rinse with water of the same temperature, followed by 10 min of forced hot air drying. Core body temperatures of the otters washed in cold water fell at a median rate of 0.1 degrees C/min, whereas otters washed in warm water maintained stable core temperatures until the completion of the protocol, at which time their core temperatures began to drop at a similar rate. Core temperatures restabilized in both groups, and no statistical difference in core temperature between groups remained 180 min after initiation of the protocol. Efforts to examine the efficacy of supplemental squalene administration to speed the recovery of fur condition and waterproofing were unsuccessful because the washing protocol did not cause loss of coat waterproofing in 8 of the 10 subjects.

Aerosols↗

Hypothalamic temperature and deep body temperature during copulation in the male rat.

The medial preoptic area (MPOA) of the hypothalamus is involved in both the expression of male sexual behavior and the regulation of physiological temperature. This duality of function led us to ask whether arousal, intromission, and ejaculation are accompanied by a distinctive temperature profile. Using telemetric thermosensors, we monitored MPOA temperature and deep body temperature during copulation in the male rat. Changes in MPOA temperature were highly uniform, more so than changes in body temperature. The MPOA heated prior to ejaculation, cooled rapidly following ejaculation and then began to heat again coincident with the termination of the post-ejaculatory refractory period. These changes could not be related to variations in general activity. The most striking change in MPOA temperature, rapid cooling following ejaculation, was explained in terms of certain behaviorally-induced hemodynamic events.

Animals↗