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

The divalent cationic ionophore A23187 (calimycin) facilitates the transport of calcium ions across biological membranes, resulting in an increase of cytosolic calcium. A23187 has been used extensively in vitro to activate calcium-dependent neurocellular processes. Because of its potential usefulness as a neurotoxicological probe, our laboratory conducted a series of studies to characterize the neurofunctional consequences of A23187 in the intact organism. In addition to approximating the LD50, the effects of acute parenteral administration of A23187 on conditioned avoidance, nociceptive shock threshold, open-field activity, consummatory behavior, body temperature and neuromotor function, including general activity, coordination, balance and grip strength, were assessed in the rodent. The LD50 of A23187, administered intraperitoneally to adult male rats, was 9.2 mg/kg. The predominant overt signs of toxicity included lethargy, limb weakness and apnea. Lower doses, from 0.5 to 0.03 mg/kg, produced a variety of more subtle neurobehavioral effects, including a selective depression of motor activity, a moderate elevation of shock threshold, altered conditioned avoidance behavior and hypothermia.
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PMID:Neurobehavioral effects of the calcium ionophore A23187. 311 83

To evaluate the hypothesis that depressed neuromuscular transmission causes dithiobiuret (DTB)-induced muscle weakness in rats, the temporal development of impaired treadmill performance and deficits in the nerve-elicited muscle contractions were compared during daily treatment with the toxicant (DTB, 1 mg/kg/day X 6 days). Diminished treadmill test performance after 4 days of treatment marked the initial detection of impaired motor function. At this time fading (loss of tension during tetanus) of gastrocnemius contractions elicited in response to 100-Hz sciatic nerve stimulation occurred in DTB-treated rats but not in controls. After 5 and 6 days of treatment, treadmill failure became complete, tetanic fade worsened dramatically, and peak contractile tension measured during trains of nerve stimulation (10-250 Hz) decreased progressively. Appearing by Day 6 were marked body weight loss, dehydration, hypothermia, and a depression in serum concentrations of thyroid hormones. Total oxygen content of the blood was not reduced at any time during treatment, and serum concentrations of glucose, sodium, potassium, calcium, chloride, and phosphorus in DTB-treated rats on Day 6 were similar to those of control animals. Therefore, hypoxia, hypoglycemia, or a serum electrolyte imbalance do not initiate or modulate the neuromuscular toxicity. Light microscopic evaluation of liver, kidney, lung, thyroid, and other organs in intoxicated rats was unremarkable and in skeletal muscles and selected sites of brain, spinal cord, and sciatic nerve no morphologically significant lesions were observed. Even when DTB-intoxicated rats were maintained in a state of flaccid muscle weakness for 5 continuous days, peripheral nerve lesions proximal to the intramuscular nerves were not detected. Thus, depressed neuromuscular transmission appears to be the primary cause of the flaccid muscle weakness and no evidence was obtained that nonneural effects of DTB initiate or modulate this effect.
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PMID:Temporal analysis of dithiobiuret neurotoxicity in rats and assessment of potential nonneural causes. 311 11

Brief perfusion of heart with calcium-free medium renders myocardial cells calcium-sensitive so that readmission of calcium results in uncontrolled Ca2+ entry and acute massive cell injury (calcium paradox). We investigated the hypothesis that polyamines may be involved in the mediation of abnormal Ca2+ influx and cell damage in the calcium paradox. The isolated perfused rat heart was used for these studies. Calcium-free perfusion promptly (less than 5 min) decreased the levels of polyamines and the activity of their rate-regulating synthetic enzyme, ornithine decarboxylase (ODC), and calcium reperfusion abruptly (less than 15-180 s) increased these components. alpha-Difluoromethylornithine (DFMO), a specific suicide inhibitor of ODC, suppressed the calcium reperfusion-induced increase in polyamines and the concomitant increase in myocardial cellular 45Ca influx, loss of contractility, release of cytosolic enzymes, myoglobin, and protein, and structural lesions. Putrescine, the product of ODC activity, nullified DFMO inhibition and restored the calcium reperfusion-induced increment in polyamines and the full expression of the calcium paradox. Putrescine itself enhanced the reperfusion-evoked release of myoglobin and protein in the absence of DFMO. Hypothermia blocked the changes in heart ODC and polyamines induced by calcium-free perfusion and calcium reperfusion and prevented the calcium paradox. These results indicate that rapid Ca2+-directed changes in ODC activity and polyamine levels are essential for triggering excessive transsarcolemmal transport of Ca2+ and explosive myocardial cell injury in the calcium paradox.
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PMID:Polyamines mediate uncontrolled calcium entry and cell damage in rat heart in the calcium paradox. 311 63

Forty-one patients who underwent cardiac surgery under conditions of systemic hypothermia and intermittent cold crystalloid potassium cardioplegia were studied, in order to elucidate the effects of ventricular fibrillation and reperfusion on the myocardium, by using the intramyocardial pCO2 and temperature sensor. All patients were assigned to 2 groups, namely; group A (21 cases), in which the time between the aorta declamping and defibrillation was under 10 minutes, and group B (20 cases) in which the time was over 10 minutes. In both groups A and B, myocardial pCO2 increased at the rate of 3.58 +/- 1.70 and 2.16 +/- 0.62 mmHg/min (p less than 0.05) after aorta declamping, respectively and the myocardial pCO2 decreased at the rate of 5.59 +/- 0.60 and 4.18 +/- 0.76 mmHg/min (p less than 0.05) after defibrillation, respectively. In group A, the myocardial calcium content, pre-CPB (cardio pulmonary bypass) was 10.98 +/- 1.62 nmol/mg/dry weight and at the time of aorta declamping it was 15.90 +/- 1.81 nmol/mg/dry weight (p less than 0.05). In group B, the myocardial calcium content, pre-CPB, was 14.62 +/- 2.15 nmol/mg/dry weight and at the time of aorta declamping it was 18.23 +/- 4.36 nmol/mg/dry weight (p less than 0.05). At both three and six hours after the operation, the left ventricular work index per minute (LVWI) in group A showed better cardiac pump function than that in group B. We therefore conclude that when reperfusion is encountered, acidosis can be minimized by prompt defibrillation.
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PMID:Myocardial tissue pCO2 and calcium content during ventricular fibrillation and reperfusion periods. 314 51

Of all tissues of the extremities, muscle is the least tolerant of ischemia. Hypothermia of tissue is considered beneficial for the maintenance of viability of muscle in amputated limbs before surgical replantation, but it has never been established that conventional cooling in an ice bath or its equivalent (temperature of tissue, approximately 1 degree Celsius) is the optimum level of hypothermia for minimizing metabolic derangement in ischemic muscle. In this study, we first defined the time course and level of metabolic derangement of muscle in twenty-eight ischemic hind limbs in cats at 22, 15, 10, 5, and 1 degree Celsius. The levels of adenosine triphosphate and phosphocreatine and the mean intracellular pH of the muscles in the lateral aspect of the thigh in each limb were monitored with phosphorus nuclear magnetic-resonance spectroscopy over time. The excised muscles from six freshly amputated legs of live humans were then similarly studied to determine whether muscles from cats and from humans exhibit comparable bioenergetic responses to hypothermic ischemia. A final series of ten ischemic hind limbs from cats was studied by nuclear magnetic resonance and muscle biopsy for direct biochemical assay of tissue energy metabolites to compare the metabolic benefits of two different methods of preserving limbs: continuous cooling in an ice bath, and a newly devised protocol for the rapid induction and maintenance of so-called intermediate (10 +/- 5 degrees Celsius) hypothermia of tissue. Ischemic skeletal muscle in cats exhibited a paradoxical metabolic response to extreme cold (1 degree Celsius). The rate of metabolic deterioration progressively declined with decreasing temperature of tissue to 10 degrees Celsius. However, at 5 degrees Celsius, no additional benefit was detected, and at 1 degree Celsius, there was a significant acceleration in the rates of degradation of adenosine triphosphate and phosphocreatine and in the production of lactate. The rate of degradation of adenosine triphosphate in human ischemic muscle was also faster at 1 degree Celsius than at 10 degrees Celsius. This paradoxical response is apparently due to a severe inhibition of the calcium pump of the sarcoplasmic reticulum of the muscle cell at temperatures of less than 5 degrees Celsius. The inhibition permits an efflux of calcium to the myofibrils, which stimulates both glycolysis and the degradation of adenosine triphosphate by myofibrillar adenosine triphosphatase.
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PMID:The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia. 319 76

No drug that is used for brain protection after global brain ischaemia as a result of cardiac arrest has been shown to be of benefit. Barbiturate agents have been proved not to be beneficial whereas studies of calcium-channel blocking drugs are inconclusive. Hypothermia, haemodilution and mechanical hyperventilation are not of proven benefit. Immediate defibrillation with rapid restoration of blood pressure is the best method to improve the neurological outcome after a cardiac arrest. After severe head injury, prompt emergency care to restore ventilation, oxygenation and blood pressure improves the neurological outcome. The early evacuation of extracerebral intracranial haematomas also improves the outcome. Corticosteroid therapy does not improve the outcome. The monitoring of intracranial pressure and the control of increased intracranial pressure by hyperventilation, cerebrospinal-fluid drainage and mannitol, frusemide and barbiturate therapy appear to improve the outcome after a severe head injury, although this has not been proved by randomized controlled studies.
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PMID:Brain resuscitation and protection. 328 7

Calcium channel blockade has been shown to prevent warm renal ischemic damage. The ability of verapamil to decrease the severity of acute tubular necrosis (ATN) after 24-hr cold storage and autotransplantation was studied in a randomized paired study of 12 dogs. Experimental animals pretreated with intraarterial verapamil and flushing of the harvested kidney with cold intracellular solution containing verapamil demonstrated significantly (P less than .05) greater renal function preservation over their matched controls. A subsequent nonpaired study of 6 dogs treated only with flushing of the harvested kidney with perfusate containing verapamil demonstrated no significant preservation advantage over controls. We conclude that verapamil, administered prior to the ischemic event, can enhance the protective effect of hypothermia and decrease the severity of ATN in ischemically injured kidneys.
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PMID:The effect of verapamil in reducing the severity of acute tubular necrosis in canine renal autotransplants. 330 60

Presently myocardial protection can be obtained in three main ways: 1) energy conservation through chemical induction of rapid and complete diastolic arrest, 2) slowing of the metabolic rate and degradative process through the use of hypothermia, and 3) prevention or reversal of unfavourable ischemic-induced changes with various protective agents. These methods of myocardial protection and their effectiveness, the calcium metabolism during myocardial ischemia, and the effects of calcium channel blockers are briefly reviewed and discussed. It is stressed that myocardial protection during ischemic arrest is a complex entity, and that new modes of myocardial protection are needed in the future.
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PMID:Cardioplegia and myocardial ischemia during cardiopulmonary bypass. 352 Nov 95

Two solutions, our cardioplegic solution and Collins' solution, were tested with regard to preservation of the heart under deep hypothermia before transplantation. The setup used was the isolated perfused working rat heart model and 4 hours of preservation at 0 degree C. The following three groups were prepared: Group 1: the heart was arrested with the cardioplegic solution (potassium: 20 mmol/L, sodium: 87 mmol/L) and then flushed with and stored in Collins' solution (potassium: 117 mmol/L, sodium: 10 mmol/L); Group 2: the heart was arrested with and stored in Collins' solution; and Group 3: the heart was arrested with and stored in the cardioplegic solution. The recovery of cardiac function was more satisfactory in Group 1 than in Groups 2 and 3. The increase in lactate was greater, and adenosine triphosphate and total adenine nucleotide were more depleted during storage in Group 2 than in Groups 1 and 3. In Group 3 myocardial sodium accumulation and potassium depletion during storage were greater than in Groups 1 and 2, and myocardial sodium and calcium overload after reperfusion were greater than in Group 1. Myocardial calcium overload after reperfusion in Group 2 was also greater than that in Group 1. These findings plus coronary vascular resistance analysis revealed that Collins' solution damages the heart during arrest procedures and that the cardioplegic solution is less effective for storage of the arrested heart under deep hypothermia. Therefore the heart should be first arrested with the cardioplegic solution and then flushed with and kept in Collins' solution for simple cold storage.
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PMID:Cold storage of the rat heart for transplantation. Two types of solution required for optimal preservation. 354 Apr 58

The effect of the calcium and oxygen contents of a hyperkalemic glucose-containing cardioplegic solution on myocardial preservation was examined in the isolated working rat heart. The cardioplegic solution was delivered at 4 degrees C every 15 minutes during 2 hours of arrest, maintaining a myocardial temperature of 8 degrees +/- 2 degrees C. Hearts were reperfused in the Langendorff mode for 15 minutes and then resumed the working mode for a further 30 minutes. Groups of hearts were given the oxygenated cardioplegic solution containing an ionized calcium concentration of 0, 0.25, 0.75, or 1.25 mmol/L or the same solution nitrogenated to reduce the oxygen content and containing 0 or 0.75 mmol ionized calcium per liter. The myocardial adenosine triphosphate concentrations at the end of arrest in these six groups of hearts were 15.6 +/- 1.2, 9.5 +/- 0.5, 8.2 +/- 1.1, 4.9 +/- 1.8, 10.1 +/- 2.0, and 1.6 +/- 0.4 nmol/mg dry weight, respectively. At 5 minutes of working reperfusion, the percentages of prearrest aortic flow were 80 +/- 2, 62 +/- 4, 33 +/- 6, 37 +/- 5, 48 +/- 7 and 46 +/- 8, respectively. The differences among the groups in adenosine triphosphate concentrations and in functional recovery diminished during reperfusion. In hearts given the hypoxic calcium-containing solution, there was a marked increase in coronary vascular resistance during the administration of successive doses of cardioplegic solution, which was rapidly reversible upon reperfusion. These data indicate that hearts given the acalcemic oxygenated solution had better adenosine triphosphate preservation during arrest and better functional recovery than hearts in any other group. Addition of calcium to the oxygenated cardioplegic solution decreased adenosine triphosphate preservation and functional recovery. Oxygenation of the acalcemic solution increased adenosine triphosphate preservation and functional recovery. The lowest adenosine triphosphate levels at end arrest were observed in hearts given the hypoxic calcium-containing solution. In the setting of hypothermia and multidose administration, the addition of calcium to a cardioplegic solution resulted in increased energy depletion during arrest and depressed recovery.
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PMID:Optimal myocardial preservation with an acalcemic crystalloid cardioplegic solution. 357 97


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