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

From March 1991 through July 1992, 1,001 patients having elective coronary artery bypass grafting were randomized to receive either continuous warm (> or = 35 degrees C) blood cardioplegia with systemic normothermia (> or = 35 degrees C) or intermittent cold (< or = 8 degrees C) oxygenated crystalloid cardioplegia and moderate systemic hypothermia (< or = 28 degrees C). Preoperative variables including age, sex, prior coronary bypass grafting, hypertension, prior myocardial infarction, diabetes, angina class, and preoperative heart failure class were similar in both groups, as were the intraoperative variables of number of coronary grafts, mammary artery use, and cardiopulmonary bypass time. Aortic cross-clamp time was significantly longer in the warm group (46 +/- 23 minutes versus 40 +/- 21 minutes). Most postoperative variables including mortality (warm, 1.0%, and cold, 1.6%), Q wave infarction (warm, 1.4%, and cold, 0.8%), and need of an intraaortic balloon pump (warm, 1.4%, and cold, 2.0%) were similar between groups. Total neurologic events (warm, 4.5%, and cold, 1.4%; p < 0.005) and perioperative strokes (warm, 3.1%, and cold, 1.0%; p < or = 0.02) were significantly higher in the warm group. Neurologic events included perioperative stroke (warm, 15 patients, and cold, 5 patients; p < 0.02), perioperative encephalopathy (warm, 2 patients, and cold, 1 patient), and delayed (> or = 3 in-hospital days) stroke (warm, 5 patients, and cold, 1 patient). All patients experiencing a stroke had a persistent neurologic deficit at the time of discharge. Encephalopathy resolved completely in all instances.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prospective, randomized trial of retrograde warm blood cardioplegia: myocardial benefit and neurologic threat. 784 93

Since 1970 we have investigated postischemic anoxic encephalopathy and potential treatments for cerebral resuscitation after cardiac arrest by cardiopulmonary-cerebral resuscitation (CPCR). The post-resuscitation syndrome has been studied at the levels of cell, organ, organism and community. Short-term and long-term models in rats, dogs, and monkeys have been developed, and an international multicenter randomized clinical trial mechanism was established. Clinical studies disproved the 5-min limit of reversible cardiac arrest and yielded other valuable data on treatments and prognostication. Thiopental loading or calcium entry blocker therapy (lidoflazine) gave no significant improvement in patients. Free radical scavengers are under investigation in the laboratory. We hypothesize that post-arrest perfusion failure and necrotizing cascades require etiology-specific combination treatments. Standard (control) therapy in a current dog model of cardiac arrest (no flow) of 12.5-20 min, reperfusion with cardiopulmonary bypass, and intensive care for 72-96 h has consistently resulted in survival with brain damage. After ventricular-fibrillation (VF) arrest of 17 min, moderate hypothermia (28-32 degrees C) inconsistently improved cerebral outcome. After VF arrest of 12.5 min, hypertension plus hemodilution normalized the local (multifocal) cerebral hypoperfusion post-arrest and, again, inconsistently improved cerebral outcome. Additional mild hypothermia (34-36 degrees C), however, consistently improved cerebral outcome, whether induced before or during and after arrest.
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PMID:Systematic development of cerebral resuscitation after cardiac arrest. Three promising treatments: cardiopulmonary bypass, hypertensive hemodilution, and mild hypothermia. 842 45

Repeated administration of thioacetamide (TAA) to CD1 mice produced hepatic failure and biochemical and behavioral effects characteristic of hepatogenic encephalopathy (HE). The symptoms in mice resembled those previously observed in rats after similar treatments. It is, however, obvious that both in rats and mice the severity of symptoms depends not only on dose and dosing schedule of TAA, but also on strain and body weight (age). Administration of 5-fluoromethylornithine (5FMOrn), a selective inactivator of ornithine aminotransferase (OAT), significantly reduced mortality, and it ameliorated most of the TAA-induced pathologic symptoms, such as hypothermia, decreased locomotor and exploratory behavior, pathologic liver function and amino acid patterns. The most prominent biochemical consequence of 5FMOrn administration is the elevation of ornithine concentrations in tissues, including the brain, and in body fluids. Elevated ornithine concentrations are, therefore, the most likely basis for the therapeutic effects of 5FMOrn. In agreement with this notion is the enhancement of citrulline and urea formation. These findings and the observation that administration of ornithine in combination with a branched-chain 2-oxoacid ameliorated the pathologic symptoms of portal-systemic encephalopathy suggest inhibition of OAT in the treatment of this disease. The liver protective effect of 5FMOrn is not yet understood; the enhancement of regenerative processes is a likely explanation.
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PMID:Effects of inhibition of ornithine aminotransferase on thioacetamide-induced hepatogenic encephalopathy. 847 73

In 1961, in Pittsburgh, PA, "cerebral" was added to the cardiopulmonary resuscitation system (CPR --> CPCR). Cerebral recovery is dependent on arrest and cardiopulmonary resuscitation times, and numerous factors related to basic, advanced, and prolonged life support. Postischemic-anoxic encephalopathy (the cerebral postresuscitation disease or syndrome) is complex and multifactorial. The prevention or mitigation of this syndrome requires that there be development and trials of special, multifaceted, combination treatments. The selection of therapies to mitigate the postresuscitation syndrome should continue to be based on mechanistic rationale. Therapy based on a single mechanism, however, is unlikely to be maximally effective. For logistic reasons, the limit for neurologic recovery after 5 mins of arrest must be extended to achieve functionally and histologically normal human brains after 10 to 20 mins of circulatory arrest. This goal has been approached, but not quite reached. Treatment effects on process variables give clues, but long-term outcome evaluation is needed for documentation of efficacy and to improve clinical results. Goals have crystallized for clinically relevant cardiac arrest-intensive care outcome models in large animals. These studies are expensive, but essential, because positive treatment effects cannot always be confirmed in the rat forebrain ischemia model. Except for a still-elusive breakthrough effect, randomized clinical trials of CPCR are limited in their ability to statistically document the effectiveness of treatments found to be beneficial in controlled outcome models in large animals. Clinical studies of feasibility, side effects, and acceptability are essential. Hypertensive reperfusion overcomes multifocal no-reflow and improves outcome. Physical combination treatments, such as mild resuscitative (early postarrest) hypothermia (34 degrees C) plus cerebral blood flow promotion (e.g., with hypertension, hemodilution, and normocapnia), each having multiple beneficial effects, achieved complete functional and near-complete histologic recovery of the dog brain after 11 mins of normothermic, ventricular fibrillation cardiac arrest. Calcium entry blockers appear promising as a treatment for postischemic-anoxic encephalopathy. However, the majority of single or multiple drug treatments explored so far have failed to improve neurologic outcome. Assembling and evaluating combination treatments in further animal studies and determining clinical feasibility inside and outside hospitals are challenges for the near future. Treatments without permanent beneficial effects may at least extend the therapeutic window. All of these investigations will require coordinated efforts by multiple research groups, pursuing systematic, multilevel research--from cell cultures to rats, to large animals, and to clinical trials. There are still many gaps in our knowledge about optimizing extracerebral life support for cerebral outcome.
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PMID:Cerebral resuscitation from cardiac arrest: treatment potentials. 860 8

Hypoxia-ischemia damages selected regions of the immature at different ages. Prior to 32 weeks gestation the periventricular white matter is selectively vulnerable but in the last trimester the basal ganglia become especially vulnerable to injury. Hypoxia-ischemia causes injury by activating a series of biochemical events that unfolds over a period of hours to days following the initial insult and we are investigating the ways in which age modifies these events. The cascade includes release of glutamate, overstimulation of excitatory amino acid receptors and raised intracellular levels of calcium. Clinically this series is manifested by hypoxic-ischemic encephalopathy (HIE), a syndrome that includes coma, seizures, a burst suppression EEG, respiratory depression and severe hypotonia. Clinical studies have established a relationship between the severity of neonatal encephalopathy and later manifestations of brain damage or cerebral palsy. Potential neuroprotective therapies need to be effective when given after the insult but the 'therapeutic time window' for most N-methyl-D-aspartate (NMDA) glutamate antagonists is limited after injury. Using a model of hypoxic-ischemic injury and neonatal rats and hypothermic-circulatory arrest in dogs, we found that immunohistochemical staining for neuronal nitric oxide synthase (nNOS) is markedly increased from 6 to 24 h after the insult in the basal ganglia and cortex. The induction of nNOS preceded the time of maximal neuronal necrosis and during the time when many apoptotic nuclei were appearing. We have also found that a brief period of 2 h of mild hypothermia (32 degrees C) following hypoxia-ischemia in neonatal rats delayed neuronal necrosis by more than a week. We are determining whether this delay is related to a change in nNOS activation. Induction of nNOS in the post-insult period may contribute to expression of injury and signs of encephalopathy following a hypoxic-ischemic insult.
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PMID:Hypoxic and ischemic disorders of infants and children. Lecture for 38th meeting of Japanese Society of Child Neurology, Tokyo, Japan, July 1996. 918 71

Intraischemic reduction in temperature of 2-3 degrees C (modest hypothermia) has been demonstrated to provide partial neuroprotection in neonatal animals. This investigation determined if modest hypothermia initiated immediately after brain ischemia provides neuroprotection. Piglets were studied with rectal temperature maintained during the 1st h after 15 min of brain ischemia at either 38.3 +/- 0.3 degrees C (normothermia, n = 11) or at 35.8 +/- 0.5 degrees C (modest hypothermia, n = 11). The severity of brain ischemia was similar between groups as indicated by equivalent reduction in mean blood pressure (90 +/- 15 to 24 +/- 3 versus 92 +/- 13 to 26 +/- 3 mm Hg), and changes in cerebral metabolites and intracellular pH (pH(i)) measured by magnetic resonance spectroscopy (beta-nucleoside triphosphate = 44 +/- 9 versus 42 +/- 18% of control, control = 100%, pH(i): 6.25+/- .15 versus 6.24 +/- 0.22 for normothermic and modestly hypothermic groups, respectively). In the first 90 min after ischemia, there were no differences between groups in the duration and extent of brain acidosis, and relative concentrations of phosphorylated metabolites. Categorical assessment of neurobehavior was evaluated at 72 h postischemia (n = 16), or earlier if an animal's condition deteriorated (n = 6). Postischemic hypothermia was associated with less severe stages of encephalopathy compared with normothermia (p = 0.05). Histologic neuronal injury was assessed categorically in 16 brain regions, and postischemic hypothermia resulted in less neuronal injury in temporal (p = 0.024) and occipital (p = 0.044) cortex at 10 mm beneath the cortical surface, and in the basal ganglia (p = 0.038) compared with that in normothermia. Modest hypothermia for 1 h immediately after brain ischemia provides partial neuroprotection and may represent an adjunct to resuscitative strategies.
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PMID:Modest hypothermia provides partial neuroprotection when used for immediate resuscitation after brain ischemia. 921 32

Hypoxia-ischaemia produces permanent brain damage by processes that continue for many hours after reoxygenation/reperfusion. This provides a window of opportunity for therapy aimed at preventing further loss of brain cells. Reducing brain temperature by 2-6 degrees C for 3-72 h after reoxygenation/reperfusion has been shown to reduce brain damage by 25-80% in controlled trials with six different neonatal animal models of hypoxia-ischaemia. No adverse effects from mild hypothermia have been documented. The mechanisms of protection are unknown but may include a reduction in extracellular excitotoxic amino acids, reduced nitric oxide synthesis and inhibition of apoptosis. Mild hypothermia is currently the most promising clinically feasible neural rescue therapy for full-term infants at risk of developing hypoxic-ischaemic encephalopathy, but clinical use must be restricted to approved trial protocols.
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PMID:Keeping a cool head, post-hypoxic hypothermia--an old idea revisited. 935 Aug 79

Perinatal asphyxia remains one of the most devastating neurologic processes. Although the understanding of the pathophysiology after perinatal asphyxia is extensive, there are few therapeutic interventions available to prevent or even mitigate the devastating process that unfolds after injury. The search for a safe and efficacious therapy has prompted scientists and clinicians to consider various promising therapies. One such therapy is therapeutic hypothermia. On the basis of adult, pediatric, and animal research, there is increasing evidence to suggest that therapeutic hypothermia may be an effective intervention to lessen the secondary neuronal injury that ensues after a hypoxic-ischemic insult. In this article the historic and modern-day uses of therapeutic hypothermia are first reviewed. The pathophysiology of neonatal asphyxia is examined next, with emphasis on the changes that occur when therapeutic hypothermia is implemented. Potential side-effects of the therapy in the neonate and the debate over systemic vs selective hypothermia are discussed. Lastly, although hypothermia as a potential treatment modality for neonates with hypoxic-ischemic encephalopathy is supported by numerous studies, the need for well-designed multicenter trials with detailed patient entry criteria and therapeutic conditions is emphasized.
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PMID:The use of hypothermia: a role in the treatment of neonatal asphyxia? 1042 27

This investigation determined if a short interval of modest hypothermia (1 h) initiated 30 min after brain ischemia provided neuroprotection. The rationale for the time and duration of brain cooling reflects the likelihood that the implementation of neuroprotective strategies will occur at an interval shortly after ischemia, and that long-term maintenance of normothermia is a cornerstone of neonatal stabilization. Studies were performed in 22 ventilated neonatal mini-swine in a superconducting magnet to obtain 31P magnetic resonance spectra. After a control period all animals underwent 15 min of global brain ischemia and were maintained normothermic for the first 30 min post-ischemia. In one group of 11 swine normothermia was continued. In the other group of 11 swine, modest hypothermia was initiated at 30 min post-ischemia, continued for 1 h and followed by resumption of normothermia. Animals were subsequently weaned from ventiltor support, removed from the magnet, and underwent neurobehavioral and histologic assessment at 72 h post-ischemia. Both groups had similar severity of ischemia, as indicated by identical changes in arterial blood pressure and pH, alterations in brain beta-nucleotide triphosphate (% of control where control = 100%, 32 +/- 28 vs 27 +/- 26% for normothermic and hypothermic groups, respectively), and the extent of intraischemic brain acidosis (6.13 +/- 0.19 vs 6.14 +/- 0.14 for normothermic and hypothermic groups, respectively). In both groups the distribution of stages of encephalopathy were the same: 1 normal and 10 abnormal (4 mild, 2 moderate, and 4 severe) normothermic, and, 3 normal and 8 abnormal (4 mild, 2 moderate, and 2 severe) hypothermic animals. There was no difference in the extent of neuronal injury between groups. We conclude that a 1-h interval of modest hypothermia initiated at 30 min post-ischemia does not confer neuroprotection.
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PMID:A limited interval of delayed modest hypothermia for ischemic brain resuscitation is not beneficial in neonatal swine. 1050 57

Five patients with acute encephalopathy underwent methylprednisolone pulse (mPSL-P), hypothermia and their combination therapies (3 cases, 1 case and 1 case, respectively), with excellent outcome. Two cases with severe brain edema survived. One had severe brain damage as a sequelae. The remaining one recovered well after the combination therapy with mPSL-p and mild hypothermia, despite complete obstruction of the fourth ventricle on the first CT scan; the sequelae, hemiplegia and intelligent disturbance, was only mild. Four patients who received mPSL-P therapy within 6 hours after the onset of CNS symptoms recovered well though one was left with epilepsy. These results indicate that mPSL-P and/or hypothermia therapy will be chosen as the treatment of acute encephalopathy.
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PMID:[Efficacy of methylprednisolone pulse and mild hypothermia therapies in patients with acute encephalopathy]. 1065 54


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