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

The effect of cooling and subsequent rewarming on the tissue respiration of canine hearts was studied during polycomponent ether-oxygen anaesthesia. The tests included the determinations of the activity of the dehydrogenases of the cytrate cycle, the content and activity of chromoproteids, the respiration rate of the mitochondrias on succinate, glutamate and ketoglutarate, the content of glycogen, the activity of the phosphorylases, hexokinase, lactate dehydrogenase, the content of lactate, pyruvate, adenyl nucleotides and creatine phosphate. Significant changes were noted in the content and activity of the above substances, acceleration of mitochondrial respiration, reduced energy regulation of respiration, and decreased amount of the adenyl components. It is suggested that under artificial hypothermia the processes of chromoproteids biosynthesis are enhanced, which results in an increased power of terminal respiration, and conformational rearaangements of the enzymes connected with the membranes occur.
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PMID:[Characteristics of energy metabolism in the myocardium under artificial hypothermia]. 19 79

1. The rise in blood glucose and the fall in body temperature which follows the injection of a glucose analogue, 2-deoxy-D-glucose (2-DG) into the lateral cerebral ventricle (I.C.V) of unanaesthetized rats were studied and found to be dose-dependent. These 2-DG induced responses are elicited by the impairment of glucose metabolism within central "glucoreceptors'. 2. 2DG induced hyperglycaemia and hypothermia were completely prevented and even the converse effects occurred when fivefold equimolar amounts of D-fructose were simultaneously injected I.C.V.; fructose, at equimolar doses, did not modify the effects of 2-DG. 3. D-xylose and D-ribose, even at high doses, did not influence 2-DG hyperglycaemia, but increased slightly the 2-DG induced hypothermia. This suggests that the pentose phosphate pathway is unable to support the metabolism within the glucoreceptors. 4. Pyruvate suppressed the 2-DG induced hyperglycaemia with a marked delay, while acetate (as ethyl ester) and a mixture of malate plus oxaloacetate did not prevent 2-DG induced effects. These results may be accounted for by the low dosage used. 5. Acetoacetate and 3-hydroxybutyrate did not prevent 2-DG hypothermia and hyperglycaemia. 6. An effective prevention of the 2-DG induced hyperglycaemia and hypothermia was achieved with fumarate and glutamate, indicating that the stimulation of the Krebs cycle within "glucoreceptors' removes the glucoprivic effects. 7. The results indicate that prevention of 2-DG induced effects occurred only with alternate source of metabolic fuel which can support high respiratory rates in brain tissue. It is concluded that central chemoreceptors are not specifically responsive to glucose, or hexoses, but to the rate of oxidative metabolism.
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PMID:Sensitivity of central chemoreceptors controlling blood glucose and body temperature during glucose deprivation. 115 83

We examined the ability of phenyl-t-butyl-nitrone (PBN), an electron spin trapper, to attenuate ischemia-induced forebrain edema and hippocampal CA1 neuronal loss in gerbils, and to protect rat cerebellar neurons in primary culture from glutamate-induced toxicity. PBN, given i.p. at 75 or 150 mg/kg 30 min before ischemia (5 min occlusion), increased survival (at 7 days) of CA1 neurons from 60 +/- 14 (vehicle-treated, n = 17) to 95 +/- 15 (P less than 0.05, n = 15) and 145 +/- 3 (P less than 0.01, n = 15), respectively. When gerbils were treated with PBN (50 mg/kg, i.p.) immediately and 6 h after reperfusion, followed by b.i.d. for an additional 2 days, CA1 neurons survival improved from 35 +/- 9 (vehicle, n = 20, 6 min occlusion) to 106 +/- 17 (P less than 0.01, n = 13). In gerbils exposed to a more severe ischemia (10 min), pretreatment with 150 mg/kg PBN increased the survival of CA1 neurons from 6 +/- 6 (vehicle) to 27 +/- 10 (P less than 0.05, n = 11). Pretreatment with PBN, at 150 mg/kg, reduced forebrain edema (following 15 min ischemia) by 24.7% (P less than 0.01, n = 16). PBN at 50 mg/kg, i.p. had no hypothermic effect and at 75 or 150 mg/kg caused a transient hypothermia. The presence of PBN in the brain was confirmed in microdialysis samples and brain tissue extract using HPLC. In vitro, PBN protected rat cerebellar neurons against 100 microM glutamate-induced toxicity with an EC50 value of 2.7 mM. Our results further support the concept that free radicals contribute to brain injury following ischemia and suggest the potential therapeutic application of electron spin trappers in stroke.
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PMID:Neuroprotective effects of phenyl-t-butyl-nitrone in gerbil global brain ischemia and in cultured rat cerebellar neurons. 135 99

Injection of ibotenic acid (IA), a glutamate agonist, into the ventral medullary raphe (VMR; especially the nucleus raphe magnus) of the rat produced respiratory failure and death following a predictable course of events. The response to the IA injection was characterized initially by increased respiratory frequency and was followed by pulmonary arterial hypertension, systemic arterial hypoxemia, acidosis, and hypothermia. Within 90 min apnea occurred as a terminal event in all animals. Gravimetric, bronchoalveolar lavage protein, and histological analyses revealed no evidence of pulmonary edema. Intracerebral (VMR) pretreatment with PPP, a sigma receptor agonist, or scopolamine, a muscarinic cholinergic antagonist, prevented pulmonary failure and death even though postmortem histological analysis showed VMR cell loss and gliosis consequent to the cytotoxic IA injection. Based on the results of the study, it is suggested that the VMR has a role in regulation of pulmonary blood flow. Preliminary pharmacological studies suggested that a disruption of glutamatergic and cholinergic mechanisms mediates the lethal pulmonary phenomenon.
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PMID:Respiratory failure without pulmonary edema following injection of a glutamate agonist into the ventral medullary raphe of the rat. 137 23

Hypothermia was first applied therapeutically as a local anesthetic and later was used to achieve organ protection during procedures necessitating circulatory interruption. Profound whole-body hypothermia, typically carried out in conjunction with extracorporeal bypass, has long been employed during cardiac and neurosurgical operative procedures. More recently, studies in small-animal experimental models of cerebral ischemia have provided persuasive evidence that even small decreases in brain temperature confer striking protection against ischemic neuronal injury. By contrast, small elevations of brain temperature during ischemia accelerate and extend pathologic changes in the brain and promote early disruption of the blood-brain barrier. Hypothermia retards the rate of high-energy phosphate depletion during ischemia and promotes postischemic metabolic recovery. More importantly, mild intraischemic hypothermia markedly attenuates the release of glutamate into the brain's extracellular space and significantly diminishes the release of dopamine. Similarly, the inhibition of calcium-calmodulin-dependent protein kinase II triggered by normothermic ischemia is prevented by hypothermia, as is the ischemia-induced translocation and inhibition of the key regulatory enzyme protein kinase C. Hypothermia also appears to facilitate the resynthesis of ubiquitin following ischemia. Studies of potential clinical importance have shown that moderate hypothermia is capable of attenuating ischemic damage even if instituted early in the postischemic period. In the setting of focal cerebral ischemia, moderate brain hypothermia reduces the infarct size (particularly in the setting of reversible middle cerebral artery occlusion); conversely, hyperthermia markedly increases the infarct volume. These studies underscore the importance of monitoring and regulating the brain temperature during experimental studies of cerebral ischemia to insure a consistent pathologic outcome and to avoid the false attribution of "pharmacoprotection" to drugs that reduce the body temperature. The measurement of brain temperature is now practicable in neurosurgical patients requiring invasive monitoring, and human studies have shown that cortical and cerebroventricular temperatures may exceed systemic temperatures. Mild to moderate decreases in brain temperature are neuroprotective in cerebral ischemia, while mild elevations of brain temperature are markedly deleterious in the setting of ischemia or injury. It is anticipated that controlled clinical trials of therapeutic brain temperature modulation will be undertaken over the next several years.
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PMID:Therapeutic modulation of brain temperature: relevance to ischemic brain injury. 138 56

Temperature is known to influence the extent of anoxic/ischemic injury in gray matter of the brain. We tested the hypothesis that small changes in temperature during anoxic exposure could affect the degree of functional injury seen in white matter, using the isolated rat optic nerve, a typical CNS white matter tract (Foster et al., 1982). Functional recovery after anoxia was monitored by quantitative assessment of the compound action potential (CAP) area. Small changes in ambient temperature, within a range of 32 to 42 degrees C, mildly affected the CAP of the optic nerve under normoxic conditions. Reducing the temperature to < 37 degrees C caused a reversible increase in the CAP area and in the latencies of all three CAP peaks; increasing the temperature to > 37 degrees C had opposite effects. Functional recovery of white matter following 60 min of anoxia was strongly influenced by temperature during the period of anoxia. The average recovery of the CAP, relative to control, after 60 min of anoxia administered at 37 degrees C was 35.4 +/- 7%; when the temperature was lowered by 2.5 degrees C (i.e., to 34.5 degrees C) for the period of anoxic exposure, the extent of functional recovery improved to 64.6 +/- 15% (p < 0.00001). Lowering the temperature to 32 degrees C during anoxic exposure for 60 min resulted in even greater functional recovery (100.5 +/- 14% of the control CAP area). Conversely, if temperature was increased to > 37 degrees C during anoxia, the functional outcome worsened, e.g., CAP recovery at 42 degrees C was 8.5 +/- 7% (p < 0.00001). Hypothermia (i.e., 32 degrees C) for 30 min immediately following anoxia at 37 degrees C did not improve the functional outcome. Many processes within the brain are temperature sensitive, including O2 consumption, and it is not clear which of these is most relevant to the observed effects of temperature on recovery of white matter from anoxic injury. Unlike the situation in gray matter, the temperature dependency of anoxic injury cannot be related to reduced release of excitotoxins like glutamate, because neurotransmitters play no role in the pathophysiology of anoxic damage in white matter (Ransom et al., 1990a). It is more likely that temperature affects the rate of ion transport by the Na(+)-Ca2+ exchanger, the transporter responsible for intracellular Ca2+ loading during anoxia in white matter, and/or the rate of some destructive intracellular enzymatic mechanism(s) activated by pathological increases in intracellular Ca2+.
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PMID:Effects of temperature on evoked electrical activity and anoxic injury in CNS white matter. 140 Jun 52

GABAergic inhibitory mechanisms may offer protection to neurons after global ischemia. We tested the effects of gamma-vinyl GABA, a GABA-transaminase inhibitor, via continuous infusion in the third ventricle (Alza pumps) in a gerbil model of repetitive forebrain ischemia. We used two episodes of 3 min duration with a 'reperfusion' interval of 1 h between the insults. Histological analysis was done with silver staining 5 days after the insult. Our results show that there is significant protection of the hippocampus CA1 region and substantia nigra reticulata in treated animals compared to controls. An increase in GABA levels, decrease in glutamate, or mild hypothermia, may be potential mechanisms for this protection. GABAergic agents may prove useful agents in repetitive ischemia.
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PMID:Gamma-vinyl GABA prevents hippocampal and substantia nigra reticulata damage in repetitive transient forebrain ischemia. 142 28

The effects of systemic hypothermia (33.5 degrees C) on the ischemia-evoked release of the neurotransmitter amino acids, glutamate, aspartate, gamma-amino-butyric acid (GABA) and glycine into rat cerebral cortical superfusates were evaluated in the rat four vessel occlusion model. Glutamate, aspartate and GABA, but not glycine, levels were enhanced during and following a 20 min period of ischemia. However, when compared with normothermic ischemic animals, no reductions in glutamate, aspartate or GABA levels in the superfusates were apparent either prior to, during or following forebrain ischemic episodes. Indeed, the superfusate levels of aspartate and GABA were transiently increased immediately following ischemia. Glycine levels were significantly depressed, both pre- and post-ischemia, in cortical superfusates from hypothermic animals in comparison with normothermic rats.
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PMID:The effects of hypothermia on amino acid neurotransmitter release from the cerebral cortex. 167 60

Administration of monosodium glutamate (MSG) in the neonatal period renders the rat to be alpha-MSH deficient later in life. In this study rats received MSG in their neonatal period and were examined at the age of 60 days. alpha-MSH caused hypothermia, potentiated induced hypothermia, blocked paradoxical behavioral thermoregulation, improved performance in the Morris water tank, but had no effect on pain threshold. Melanin only caused an increase in pain threshold. It is suggested that the differential effect of alpha-MSH and melanin is governed by the dopaminergic system.
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PMID:The facilitative effects of alpha-MSH and melanin on learning, thermoregulation, and pain in neonatal MSG-treated rats. 168 21

When the brain temperature was lowered by 2 degrees C from normothermic temperature, a protective effect on postischemic neuronal death was exhibited and levels of extracellular glutamate were attenuated to about half of those at normothermic brain temperature in the gerbil hippocampus. Hypothermia has been reported to confer a protective effect on ischemia-induced delayed neuronal death. The present study was carried out to quantify this protective effect of hypothermia on the degree of alteration in extracellular release of glutamate during ischemia and the final histopathological outcome in the hippocampus. Extracellular glutamate levels were measured by microdialysis. In gerbils whose brain temperature was maintained at normothermia (37 degrees C), glutamate increased during ischemia and the early period of recirculation (by 15-fold), and CA1 neurons were consistently damaged. In animals whose brain temperature was maintained at 35 or 33 degrees C during ischemia, the release of glutamate was significantly attenuated to half or a quarter, respectively, at 37 degrees C. In animals whose brain temperature was maintained at 31 degrees C during ischemia, the release of glutamate was slightly lower than that at 33 degrees C. No CA1 ischemic neuronal damage was seen in 60% of gerbils at 35 degrees C and none was seen in any gerbils at 33 and 31 degrees C. In animals whose brain temperature was maintained at 39 degrees C during ischemia, the release of glutamate was slightly higher than that at 37 degrees C, and a high mortality rate of animals (75%) was observed. Our results reinforce other recent evidence suggesting that one of the mechanisms by which lowering of the brain temperature by only a few degrees during ischemia exerts a protective effect in the hippocampus, involves the reduction of ischemia-induced glutamate release.
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PMID:Critical levels of extracellular glutamate mediating gerbil hippocampal delayed neuronal death during hypothermia: brain microdialysis study. 168 72


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