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

Neurologic injury that occurs after ischemia results from a cascade of events involving the release of various endogenous neurotoxins. A portion of the release of excitatory neurotransmitters is calcium dependent and may be attenuated by administration of calcium channel blockers. Using an in vivo model of ischemia, we studied the effects of omega-conopeptide MVIIC, a voltage-sensitive calcium channel blocker, and hypothermia (32 degrees C) on hippocampal glutamate and aspartate release in the peri-ischemic period. Thirty-four New Zealand white rabbits of either sex were anesthetized with halothane, intubated, and mechanically ventilated. Monitored variables included blood gases, mean arterial blood pressure, and the electroencephalogram. Microdialysis catheters were transversely inserted through the anterior portion of the dorsal hippocampus and perfused with artificial cerebrospinal fluid at a rate of 2 microliters/min. After stabilization period, animals were randomly assigned to one of the following groups: Control group (n = 8), 10 microM omega-conopeptide MVIIC group (n = 7), 100 microM omega-conopeptide MVIIC group (n = 7), Hypothermia group (n = 6; cranial temperature = 32 degrees C), and omega-conopeptide MVIIC + hypothermia group (n = 6; 100 microM omega-conopeptide MVIIC and cranial temperature 32 degrees C). All the rabbits were subjected to 10 minutes of global cerebral ischemia produced by neck tourniquet inflation combined with hypotension during halothane anesthesia. Conopeptide MVIIC was administered in the artificial cerebrospinal fluid used to perfuse the microdialysis catheter. In control animals, ischemia caused a significant increase in glutamate (9.7 fold) and aspartate (11.3 fold) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transient brain ischemia in rabbits: the effect of omega-conopeptide MVIIC on hippocampal excitatory amino acids. 854 94

The acute phase of spinal cord injury includes primary and secondary pathological patterns. Primary patterns include the effects of contusion, laceration, stretch of neural tissue and direct vascular trauma. These changes are irreversible. Secondary patterns include posttraumatic ischemic changes, loss of energy metabolism, oedema, release of cytotoxic substances such as free radicals, and electrolyte changes such as an increase in intracellular calcium ions. These changes may be reversible. This determines treatment strategies. Free-radical scavengers, opioid receptor antagonists include TRH and its analogues, calcium channel blockers, volume expander, osmotic diuretics, hypothermia, antioxidants, cycloxygenase inhibitors, serotonin antagonists and NMDA receptor antagonists were tested in experimental models during the last 4 years. The successful treatment should break the feedback loops and trails of secondary injury cascade in many places so combined treatment connected with many elements and surgery decompression is necessary.
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PMID:[The physiopathology of acute spinal cord injury and a hope for a successful treatment]. 865 40

Brain damage due to an episode of cerebral hypoxia/ischemia remains a major problem in the human infant, providing impetus for the testing of potential neuroprotective agents in animal models. Although these animal models do not mirror the human pathology exactly (e.g., with respect to regions vulnerable to damage), they usually have the histological characteristics of gray matter hypoxic/ischemic injury in the human. An important factor in comparing models directly is the stage of development of the brain at birth, which varies widely between species. Approaches to prevent or treat cerebral hypoxic/ischemic damage in neonates have paralleled those in adults. However, most of these results should be interpreted cautiously, since neonatal rat models with little concurrent physiological monitoring are often used. As in adults, moderate hypothermia during the insult or a preconditioning stress prior to the insult has prevented hypoxic/ ischemic brain damage. Different from adults is the demonstration that pretreatment with moderate doses of glucocorticoids or hyperglycemia during the hypoxic/ ischemic insult protects the brain against infarction. Partial protection, primarily in neonatal rats, has also been produced by pretreatment with voltage-sensitive calcium channel antagonists, free radical scavengers, growth factors, gangliosides, anticonvulsants, antiinflammatory agents, and nitric oxide synthase inhibitors. Posttreatment has been effective with a few agents. The most consistent has been the protective effect observed with glutamate receptor antagonists administered before but also up to 4 h after the insult. The effects of most of these therapies on blood glucose, body temperature, and/or the systemic circulation should be measured and the protective effects confirmed in larger species prior to considering clinical applications.
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PMID:Brain damage due to cerebral hypoxia/ischemia in the neonate: pathology and pharmacological modification. 872 85

This article reviews cellular energy transformation processes and neurochemical events that take place at the time of brain injury and shortly thereafter emphasizing hypoxia-ischemia, cerebrovascular accident, and traumatic brain injury. New interpretations of established concepts, such as diffuse axonal injury, are discussed; specific events, such as free radical production, excess production of excitatory amino acids, and disruption of calcium homeostasis, are reviewed. Neurochemically-based interventions are also presented: calcium channel blockers, excitatory amino acid antagonists, free radical scavengers, and hypothermia treatment. Concluding remarks focus on the role of clinical neuropsychologists in validation of treatment interventions.
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PMID:Neurochemical mechanisms in brain injury and treatment: a review. 894 54

Rats genetically selected for their different ethanol voluntary consumption, UChA (low consumer) and UChB (high consumer) were used. Naive UChA and UChB rats or submitted to ethanol chronic exposure, received an i.p. dose of ethanol (2.76 g/kg) alone or 30 min after an oral dose of diltiazem (10 mg/kg), a calcium channel blocker. A significant potentiation of the narcosis and hypothermia induced by the dose of ethanol was observed in UChA diltiazem-pretreated rats not previously exposed to ethanol, while no potentiation in narcosis time appears in UChA rats chronically exposed to ethanol that acquire tolerance. In the UChB line of rats, diltiazem did not potentiate ethanol depressant actions in naive or chronic ethanol-exposed rats. Diltiazem did not modify ethanol blood levels. These results indicate that the inhibition of voltage-dependent calcium channels can exaggerate ethanol-induced effects in naive rats but not when tolerance was developed. Results suggest that UChB rats may have some innate tolerance that may be due to genetic difference in calcium channel function.
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PMID:Effect of calcium channel blocker diltiazem on some depressant actions of ethanol in UChA and UChB rats. 901 19

The injured brain may be damaged by primary impact, secondary injury from secondary damage due to initiation of destructive inflammatory and biochemical cascades by the primary injury or secondary ischemic injury following secondary insults that initiate or augment these immunological and biochemical cascades. Cerebral ischemia will arise whenever delivery of oxygen and substrates to the brain fall below metabolic needs. Many factors lead to the development of secondary insults to the injured brain during initial resuscitation, transport, surgery, and subsequent intensive care. Continuous monitoring of cerebral oxygenation (jugular oximetry, brain tissue PO2) and cerebral blood flow velocity (transcranial Doppler ultrasonography) in patients with brain trauma reveals multiple episodes of transient hypoperfusion with an adverse relationship between incidence and outcome. Secondary brain insults arise through systemic or intracranial mechanisms that reduce cerebral blood flow from compromised CPP, vascular distortion or cerebrovascular narrowing or lower oxygen delivery from hypoxemia associated with airway obstruction, pulmonary pathology, or anemia. Secondary brain ischemia remains a common pathway to secondary brain damage in most critically ill neurosurgical patients. In the future prevention of secondary brain injury may well hinge on giving a cocktail of novel agents that modify destructive biochemical and inflammatory pathways, each having a potential therapeutic window possibly in a subgroup of patients. To date, phase 3 clinical trials of several agents including PEGSOD and tyrilizad mesylate have failed to show relevant efficacy after brain trauma or subarachnoid hemorrhage. The therapeutic role of calcium channel blockers in traumatic subarachnoid hemorrhage is currently under investigation following the results of subgroup metaanalysis. Several phase 3, NMDA receptor antagonist studies are underway in brain trauma with results expected soon. Although we know that secondary insults promote excitotoxic secondary brain damage there is currently no pharmacological intervention with proven efficacy and, therefore, detection and correction of secondary insults appear to offer the best therapeutic strategy. After brain trauma, systemic hypotension, compromised CPP, raised ICP, elevated temperature, hypoxemia, and jugular bulb venous desaturation are associated with poor prognosis. Clinical trials of moderate hypothermia following brain trauma are ongoing. Following adult brain trauma maintenance of CPP above at least 65 mmHg (probably > 40 mmHg in children below 8 years) seems important to improve outcome indicating the need for continuous ICP monitoring during intensive care of brain-injured patients.
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PMID:Mechanisms and prevention of secondary brain damage during intensive care. 970 38

Secondary brain damage, following severe head injury is considered to be a major cause for bad outcome. Impressive reductions of the extent of brain damage in experimental studies have raised high expectations for cerebral neuroprotective treatment, in the clinic. Therefore multiple compounds were and are being evaluated in trials. In this review we discuss the pathomechanisms of traumatic brain damage, based upon their clinical importance. The role of hypothermia, mannitol, barbiturates, steroids, free radical scavengers, arachidonic acid inhibitors, calcium channel blockers, N-methyl-D-aspartate (NMDA) antagonists, and potassium channel blockers, will be discussed. The importance of a uniform strategic approach for evaluation of potentially interesting new compounds in clinical trials, to ameliorate outcome in patients with severe head injury, is proposed. To achieve this goal, two nonprofit organizations were founded: the European Brain Injury Consortium (EBIC) and the American Brain Injury Consortium (ABIC). Their aim lies in conducting better clinical trials, which incorporate lessons learned from previous trials, such that the succession of negative, or incomplete studies, as performed in previous years, will cease.
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PMID:Clinical trials in head injury. 1040 3

Disturbances in intracellular calcium have been implicated in liver graft damage after cold preservation and warm reperfusion. Despite improvements noted with the use of calcium channel blockers, such as nisoldipine, the exact nature and cellular basis of the presumed changes in intracellular calcium as well as the actual target of these blockers remain unclear. Isolated rat parenchymal, endothelial, and Kupffer cells were cultured and changes in intracellular calcium measured in vitro after acute hypothermia (5-8 degrees C) by fluorescence imaging using FURA-2. Between 50 and 80% of parenchymal, endothelial, and Kupffer cells exhibited significant increases in baseline calcium that were gradual and sustained for the duration of acute hypothermia. Removal of extracellular calcium completely abolished the positive response of hepatocytes and diminished the proportion of responding endothelial and Kupffer cells. The calcium channel blocker nisoldipine (1 microM) slightly diminished the proportion of positive responders in parenchymal but not in endothelial or Kupffer cells. However, nisoldipine did not modify the amplitude of the calcium rise in responding cells of all types. Acute hypothermia causes calcium influx into a majority of parenchymal, endothelial, and Kupffer cells. Nisoldipine does not effectively prevent these changes in intracellular calcium. Pathways of calcium entry resistant to the drug or other than voltage-dependent calcium channels may thus be involved.
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PMID:Changes in intracellular calcium induced by acute hypothermia in parenchymal, endothelial, and Kupffer cells of the rat liver. 1045 2

Cerebral hypoxia-ischemia in the perinatal period continues to be a major contributor to chronic neurologic impairment in children worldwide. Extensive research conducted in the past several years has led to a better understanding of the mechanisms involved in hypoxic-ischemic brain injury. Based on this understanding, the major potential therapeutic approaches being studied include antagonists of excitatory amino acids, calcium channel antagonists, free-radical scavengers, nitric oxide synthase inhibitors, anti-inflammatory agents, trophic factors, and hypothermia. Several agents are in clinical trial phases in adults. However, safety concerns and close relationship between pathomechanisms of hypoxic-ischemic cerebral injury and normal developmental processes have contributed to the slow pace in the neonatal trials. Large multicenter trials including an adequate number of infants will be needed to evaluate efficacy of therapeutic interventions in this particular age group. A large number of risk factors that predispose to hypoxic ischemic injury have been identified. It is important to control these factors and prevent brain damage in the first place. This is especially true for developing countries where resources for treatment with newer agents (when they become available) are likely to be limited. Recent information regarding mechanisms of injury and potential therapeutic measures related to perinatal age are presented in this paper.
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PMID:Hypoxic-ischemic brain damage in perinatal age group. 1079 99

Objectives were to identify and to evaluate controlled trials of interventions for term infants developing hypoxic-ischaemic encephalopathy. Five randomized trials concerning prophylactic anticonvulsant therapy for neonatal HIE were identified. There were methodological problems with all of them, and meta-analysis of barbiturate prophylaxis showed no significant effect on death or disability. One randomized trial of allopurinol showed short-term benfits, but was too small to test death or disability. One small randomized trial of hypothermia found no adverse effects, but was too small to examine death or disability. No adequate trials of dexamethasone, calcium channel blockers, magnesium sulphate, or naloxone have yet been completed, but pilot studies in infants have shown the risks of magnesium sulphate and calcium channel blockers.
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PMID:Systematic review of therapy after hypoxic-ischaemic brain injury in the perinatal period. 1080 48


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