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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this paper, we present examples of some of the several behaviors which have been taken to indicate the reinforcing efficacy of drugs, including ethanol. Efforts to identify the genetic determinants of these behaviors have employed diverse pharmacogenetic methods. For example, we have used selective breeding to develop mice selected for severe or attenuated ethanol withdrawal and have found that Withdrawal Seizure Prone mice show a greater conditioned preference for ethanol-associated locations than the selected Withdrawal Seizure Resistant line. Similarly, HOT mice, selected for insensitivity to ethanol-induced hypothermia, had greater conditioned place preference after ethanol training than COLD mice, selected for ethanol hypothermic sensitivity. We have also developed selected mouse lines responsive or unresponsive to ethanol-stimulated locomotor activity. These FAST and SLOW lines develop sensitization rather than tolerance to ethanol-induced activity. Using inbred strains of mice, others had shown that strains differed in preference for drinking ethanol solutions. We found that these strains also differed in acceptance of ethanol. Single-gene techniques have been used to show that preference drinking is significantly altered in mutant rodent strains lacking hypothalamic vasopressin, or with nephrogenic diabetes insipidus. In a specific panel of Recombinant Inbred mouse strains, we found that a single gene appeared to control a significant portion of the variance in preference drinking. These examples show that traits putatively related to drug reinforcement show substantial genetic control. Specifically, single-gene methods show promise of identification and mapping of genes related to drug reinforcement.
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PMID:Genetic determinants of ethanol reinforcement. 163 89

Mice selectively bred for resistance (HOT) and sensitivity (COLD) to the hypothermic effect of EtOH were tested for their hypothermic response to neurotransmitter-specific drugs and for the effect of such drugs on EtOH induced hypothermia (HT). The drugs administered were the opiate drugs morphine, levorphanol and U50488H, the dopamine agonists apomorphine, LY171535 and SKF38393, the dopamine antagonist chlorpromazine, the alpha adrenergic agonist St587, the cholinergic agonist nicotine and amphetamine, which increases the release of catecholamines. All of the drugs tested, with the exception of SKF38393 and amphetamine, induced a hypothermic response in HOT and COLD mice. SKF38393 had no effect on body temperature or HT produced by EtOH. Amphetamine caused HT at low doses and hyperthermia at high doses. COLD mice were more sensitive than HOT mice to the hypothermic effect of morphine and levorphanol, mu-opiate agonists, and U50488H, a relatively specific kappa agonist. All of the other drugs tested were approximately equally potent in HOT and COLD mice. These results suggest that the differential sensitivity of HOT and COLD mice to EtOH-induced HT may be partially mediated through genetic changes in opiate mechanisms.
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PMID:Effect of neurotransmitter-selective drugs in mice selected for differential sensitivity to the hypothermic actions of ethanol. 167 79

The hyperglycemic and hypothermic responses to acute ethanol exposure (0, 2, 4, 6 g/kg, intraperitoneally) were examined in non-fasted mice selectively bred for sensitivity (COLD line) or insensitivity (HOT line) to ethanol-induced hypothermia. Blood samples and rectal temperatures were obtained immediately before injection and hourly for 4 hr after injection. As expected, COLD mice demonstrated greater and more prolonged reductions in body temperature than HOT mice, especially at the 4 g/kg dose (HOT: -2.58 degrees C, COLD: -5.08 degrees C). Ethanol produced significant dose-dependent elevations in blood glucose levels over the 4-hr sampling period in both lines. The greatest elevations in blood glucose levels were seen at 4 g/kg, with COLD mice (mean = 225.1 mg/dl) showing significantly greater elevations in blood glucose levels compared to HOT mice (mean = 177.0 mg/dl). These results support the hypothesis that the thermic and glycemic effects produced by ethanol are due to related neural processes that share a common genetic component.
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PMID:The relationship between ethanol-induced hyperglycemia and hypothermia: evidence of genetic correlation. 192 51

Mice selectively bred for resistance (HOT) and sensitivity (COLD) to the hypothermic effect of an acute dose of ethanol were tested twice during the course of genetic selection for their hypothermic response to other alcohols and sedative hypnotics. The drugs administered were ethanol, propanol, n-butanol, t-butanol, pentanol, diazepam, phenobarbital, pentobarbital, methyprylon and ethchlorvynol, all of which have sedative effects on the central nervous system, and hydralazine, a peripheral vasodilator. All drugs decreased body temperature of both HOT and COLD mice. In mice selected for seven to nine generations, COLD mice were more sensitive than HOT mice to all sedative drugs. The longer-chain alcohols were more potent than ethanol in inducing hypothermia, but the magnitude of the response difference between HOT and COLD mice appeared to be smaller. The difference between HOT and COLD mice in hypothermic sensitivity to an acute dose of ethanol was greater after 11-15 generations of selection than after seven generations. Similarly, the differential effect of the other alcohols, phenobarbital, pentobarbital, and methyprylon, on HOT and COLD mice increased with more generations of selection but to a lesser extent than ethanol. These data demonstrate that selecting for sensitivity to acute ethanol hypothermia has produced mice that are also differentially sensitive to other sedative hypnotic agents. They also support the hypothesis that the drugs used in the present study share a common mechanism of action for inducing hypothermia, which may be regulated by a common set of genes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of alcohols and other hypnotics in mice selected for differential sensitivity to hypothermic actions of ethanol. 200 89

Paraplegia is a fearful and not uncommon complication of aortic clamping in surgical procedures involving thoracic and abdominal aorta. We report a case of transient spinal cord ischemia during the early postoperative period of aortobifemoral bypass in a 69-year-old male with arteriosclerosis obliterans, hypertension, type II diabetes mellitus and COLD. The anesthetic procedure was combined (peridural + intubation and mechanical ventilation + isofluorane). Two hypotensive episodes of about 80 mmHg developed, one after induction and another in the Reanimation area. The first one had a short duration, whereas the second one required the administration of colloids, crystalloids and blood. The infrarenal aortic clamping time was 35 minutes. In the early postoperative period the patient had clinical features consistent with spinal ischemia, which progressively recovered. To prevent spinal ischemia during surgery a shorter duration than 30 minutes of aortic clamping, a higher distal perfusion pressures higher than 60 mmHg during clamping, and the attempt to exclude the least possible number of intercostal and/or lumbar vessels are recommended. Drugs (corticosteroids, naloxone) and hypothermia can be useful.
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PMID:[Spinal cord ischemia in the postoperative period of aortic surgery]. 207 98

A powerful technique for determining the role of a particular neurotransmitter in mediating a response to ethanol (EtOH) is the analysis of selectively bred lines of animals. Lines selected for sensitivity and resistance to an EtOH effect differ principally in gene frequencies for genes affecting the selected response. Hence, other differences between the lines are likely due to pleiotropic actions of those genes. We discuss behavioral pharmacological experiments in two sets of selected lines. Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) mouse lines were selected for severe and minimal handling-induced convulsions (HIC), respectively, after withdrawal from chronic EtOH inhalation. The HIC is also elevated after acute administration of low doses of convulsant drugs. WSP mice were found to be more sensitive than WSR mice to many such drugs. There was no apparent specificity of such effects to any particular neurotransmitter system. Thus, genetic determination of a behavioral response to EtOH in this case cannot be traced to the influence of a single neurotransmitter system. COLD and HOT mice were selectively bred to show severe and mild hypothermia, respectively, after acute EtOH administration. COLD mice are also more sensitive to a number of other alcohols, barbiturates, and other general central nervous system depressants. When tested for sensitivity to a number of drugs with specific effects on neurotransmitter systems, COLD and HOT mice did not differ in sensitivity to drugs affecting dopaminergic, alpha-adrenergic, or nicotinic acetylcholinergic systems. COLD mice were more sensitive, however, to opioid and serotonergic drugs. Thus, analysis of these selected lines was successful in identifying particular neurotransmitters which may be important in EtOH-induced hypothermia.
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PMID:Genetic components of ethanol responses. 218 36

Offsetting ethanol-induced hypothermia in five inbred strains of mice changed ethanol sensitivity within strains and markedly reduced differences between strains in brain sensitivity to hypnotic ethanol doses. The present study extended this work to mice selectively bred for sensitivity and resistance to ethanol-induced loss of righting reflex (LORR) and hypothermia. In all experiments LORR duration and ethanol concentrations at return of righting reflex were measured after i.p. hypnotic ethanol doses and exposure to 22 or 34 degrees C. In experiment 1, C57BL/6J, A/HeJ, 129/J, LS/lbg and SS/lbg mice were given 4.2 g/kg ethanol. In experiment 2, the same mouse genotypes were tested with different ethanol doses (2.5-4.9 g/kg) selected to produce an equivalent degree of impairment (60 min LORR duration). In experiment 3, HOT and COLD lines of mice were given 4.0 g/kg ethanol. In agreement with previous work, offsetting hypothermia reduced differences between genotypes in ethanol sensitivity. Comparisons within genotypes indicated that ethanol sensitivity in C57, A/He, SS, HOT and COLD mice increased as body temperature increased. In contrast, ethanol sensitivity in 129 and LS mice decreased as body temperature increased. These results extend previous findings indicating that body temperature during intoxication contributes to differences between genotypes in ethanol sensitivity. The present findings also suggest that there are qualitative differences in the effects of temperature on ethanol sensitivity within genotypes.
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PMID:Body temperature differentially affects ethanol sensitivity in both inbred strains and selected lines of mice. 235 24

COLD mice have been genetically selected for pronounced hypothermia (HT) after acute EtOH administration, whereas HOT mice have been selected for attenuated HT. In the current experiments, HOT and COLD mice were found to differ significantly in sensitivity to EtOH-induced HT across a range of doses: the difference was greater at higher doses. After 3 g/kg of EtOH, HOT mice displayed a 1.8 degrees C HT, whereas COLD mice had a 3.6 degrees C HT. Male mice had greater HT responses than female mice regardless of genotype. Nonselected control mice were intermediate to the HOT and COLD mice in responsiveness to EtOH. After an acute EtOH dose, HOT mice were found to have slightly lower brain EtOH concentrations than COLD mice 3 and 4 (but not 1 and 2) hr after administration of EtOH, and may have eliminated EtOH slightly more rapidly than COLD mice. When tested repeatedly in a cool ambient environment (18 degrees C), COLD mice developed tolerance to EtOH hypothermia, whereas HOT mice did not. These results confirm that sensitivity to the hypothermic effects of EtOH is influenced markedly by genotype. Furthermore, selection for neurosensitivity to EtOH has produced a correlated difference in rate or magnitude of tolerance development, which is consistent with an hypothesis of the influence of common genes determining these responses to EtOH. The difference in tolerance could not be accounted for by initial HT sensitivity differences between the lines. The HOT and COLD lines should be useful for studies of the neurobiological mechanisms of EtOH-induced HT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sensitivity and tolerance to ethanol-induced hypothermia in genetically selected mice. 272 34

Using the technique of within-family selective breeding, we have generated mouse lines that differ genetically in sensitivity to the acute hypothermia induced by injection of 3 g/kg ethanol (EtOH). After 5 generations of selection, the difference in maximal hypothermic response between COLD and HOT lines was 1.6 degrees C in the first replicate and 1.2 degrees C in the second replicate. Estimates of realized heritability were h2 = .17 in each replicate. No differences in EtOH metabolism have developed, so the differences between HOT and COLD mice are presumably in neurosensitivity. These lines of animals should be useful for studying the biological mechanisms underlying neurosensitivity to EtOH. In conjunction with other selectively bred lines, they should improve our understanding of the genetic relationships among EtOH neurosensitivity, tolerance and physical dependence.
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PMID:Genetic selection of mouse lines sensitive (cold) and resistant (hot) to acute ethanol hypothermia. 382 97

Mortality and morbidity during aortic arch aneurysm repair is high despite improvements in surgical technique which attempt to assure brain protection during surgery. We successfully managed 17 patients using deep hypothermia and circulatory arrest. Anaesthesia consisted of pancuronium, fentanyl, plus isoflurane or halothane if needed. Pulmonary artery and arterial catheters were inserted. Surface cooling was performed followed by core cooling on cardiopulmonary bypass, using a heat exchanger. Total circulatory arrest was performed when esophageal temperature reached 12-14 degrees C after previous administration of thiopentone 30 mg X kg-1, methylprednisolone 2 gm, furosemide 40 mg and mannitol 25 gm. At that time the head was packed in ice and surgical correction performed. Mean arrest time was 36.5 +/- 13 minutes at a mean oesophageal temperature of 12.5 +/- 0.75 degrees C. No serious, permanent neurological deficit was found. Tracheostomy was required in five patients of whom two had chronic obstructive pulmonary disease (COPD). Two of these patients died of adult respiratory distress syndrome (ARDS) and renal failure. The reported technique is safe and can be easily used in patients undergoing aortic arch aneurysm repair.
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PMID:Anaesthesia for aortic arch aneurysm repair: experience with 17 patients. 397 Dec 9


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