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

Ischemia of the myocardium results in a loss of ultrastructure and function. Tension generation is diminished or abolished, electrolyte imbalance occurs, and the ATP-generating capacity of the mitochondria is reduced. An intracellular accumulation of Ca2+ appears to precipitate many of these changes, the intracellular accumulation of Ca2+ being caused, in turn, by a failure of the ATP-dependent mechanisms responsible for maintaining intracellular homeostasis with respect to Ca2+. This hypothesis has been tested by the use of hypothermia, pretreatment with verapamil and a reduced extracellular Ca2+ to modify the events precipitated by an ischemic episode.
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PMID:The role of calcium in the ischemic myocardium. 700 22

Preservation of regional myocardial function, high-energy phosphate stores and ultrastructure were assessed in 28 canine hearts subjected to 2 hours of global ischemia at either 12 degrees C or 21 degrees C. The preservation achieved with a potassium arrest solution was simultaneously compared in the same heart with either a nifedipine arrest solution or a potassium plus nifedipine arrest solution. There were no statistically significant differences in regional function recovery between the three arrest solutions at either temperature. At 12 degrees C, slightly better functional preservation was noted for each solution. End-systolic chord length was significantly less elongated after preservation at the lower temperature (p = 0.03). The concentration of ATP and myocardial water content were not significantly better preserved with any solution at either temperature. Myocardial ultrastructure was well preserved regardless of the solution or temperature used. The degree of hypothermia appears to be more important to functional preservation than differences between the three solutions tested. We conclude that with respect to preservation of myocardial function, high-energy phosphate stores, water content and ultrastructure, nifedipine arrest offers no advantages over potassium arrest.
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PMID:Comparison of myocardial preservation with hypothermic potassium and nifedipine arrest. 708 50

The influence of temperature on the oxygen affinity of hemoglobin, expressed as half saturation tension P50, was investigated in male Sprague Dawley rats, which had been exposed to a cold environment for about 12 h. P50-values were determined by equilibrating blood samples to a known PO2 at different temperatures. The well known increase in oxygen affinity at low temperatures was observed, but after a longer hypothermic period this effect was diminished. This reduction of the temperature effect is manifested in a change of the ratio delta log P50/delta T from 0.022 in control experiments to 0.0115 in hypothermia. In cold adapted rats such an effect means a better oxygen supply to tissue at low body temperatures than in control animals. These changes in oxygen delivery after cold acclimatisation may partially be interpreted as the result of the decreased intraerythrocytic pH and elevated concentration of ATP found in the present study.
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PMID:Diminution of the temperature effects on the oxygen affinity of hemoglobin after prolonged hypothermia. 719 Jun 74

The ability of hypothermia (34 degrees, 28 degrees) to preserve cardiac metabolism and performance during ischemia, was evaluated in the isolated Langendorff perfused rabbit heart. The hearts, isolated and perfused aerobically for 20', were made ischemic for 90' and their wall temperature maintained either at 37 degrees, 34 degrees and 28 degrees. The hearts were consequently reperfused at 37 degrees for 30'. Some of the hearts were frozen and assayed for ATP and CP. Others were homogenized and their mitochondria harvest, using either an EDTA free or an EDTA-containing extraction medium. The oxidative phosphorylating and ATP generating capacity of these mitochondria were established and their Ca++ content determined. The mechanical performance of the hearts, which were paced, was monitored by means of an intra-ventricular balloon filled with water and connected with a pressure transducer. The hearts that were made ischemic and maintained at 37 degrees were severely depleted in ATP and CP content, their mitochondria accumulated Ca++ and their oxidative phosphorylating activity was impaired. During reperfusion mitochondrial Ca++ was substantially increased, the capacity of the mitochondria to use O2 for state III respiration was further impaired and their ATP generating capacity reduced. Diastolic pressure increased and there was no recovery of the ability of the hearts to develop sistolic pressure. The hearts made ischemic and maintained at 28 degrees were protected. There was a less marked rise in mitochondrial Ca++ concentration after ischemia and during reperfusion; the mitochondria recovered the capacity of utilizing O2 and of generating ATP. That was coincident with and almost complete recovery of mechanical performance. Hypothermia at 34 degrees during ischemia provoked only a partial protection. These results are discussed in accordance with the hypothesis that hypothermia protects heart muscle against the deleterious effects of ischemia not only by reducing the metabolic requirement but also by maintaining intracellular homeostasis with respect to Ca++.
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PMID:[Effect and action mechanism of hypothermia to preserve the ischaemic myocardium (author's transl)]. 720 98

Cardiac muscle biopsy specimens were obtained from 33 patients undergoing open-heart surgery under K+-induced ischemic arrest in hypothermia (cardioplegic right atrial and right ventricular muscles) or under hypothermic ischemic arrest without K+-cardioplegia (noncardioplegia right atrial muscle), and sequential patterns of changes in the myocardial metabolism were studied by standard enzymatic techniques. The concentrations of the high energy phosphates were not only adequately preserved but actually exceeded the initial values in the cardioplegic muscles during the 40-min period of the ischemic arrest. In addition, elevated ammonia levels were neutralized by these muscles, and excessive variations in the myocardial intermediary metabolism were prevented. The levels of ATP were also adequately preserved by the noncardioplegic right atrial muscle during the 12-min period of ischemic arrest. But this protection was achieved at the expense of a 20% reduction in the myocardial creatine phosphate levels and other associated severe intracellular metabolic derangements. Changes in the myocardial intermediary metabolism, at the end of 12 min of ischemic arrest and at the end of 40 min of K+-cardioplegic arrest, were almost identical. The results of these studies suggest that, in contrast to the hypothermic arrest alone, K+-cardioplegia in hypothermia offers a superior myocardial metabolic preservation over an extended period of time.
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PMID:Effect of potassium-induced cardioplegia in hypothermia on myocardial energy, ammonium, and intermediary metabolism in man. 742 61

Central administration of galanin in the mouse dose-dependently blocked the hypothermia induced by the muscarinic receptor agonist, 2-ethyl 8-methyl-2,8-diazospiro[4,5]decan-1,3-dion hydrobromide, RS86 (minimum effective dose, MED = 3 nmol) and the acetylcholinesterase inhibitor tetrahydroaminoacridine, (MED = 3 nmol). This inhibitory effect was reversed over the dose range (0.1, 0.3, 1, 3 nmol) by the galanin receptor antagonist galantide (MED = 0.3 nmol). Furthermore, the ATP-sensitive K+ channel blockers glibenclamide (MED = 1 nmol) and gliquidone (10 nmol) both prevented the inhibitory effects of galanin on RS86 induced hypothermia. Glibenclamide (10 nmol) also reversed the inhibitory effects of galanin on tetrahydroaminoacridine induced hypothermia. Preincubation of rat cortical membranes with galanin (10 nM, 1000 nM) in vitro had no effect on binding affinity, receptor number or pharmacology of the rat cortical muscarinic receptor. In contrast to the high affinity of glibenclamide, galanin only weakly displaced [3H]glibenclamide binding in mouse whole brain homogenates (36% at 10 microM). These studies suggest that the inhibitory effect of galanin on cholinergically mediated hypothermia induced by RS86 and tetrahydroaminoacridine may be exerted via an action at ATP-sensitive K+ channels but is unlikely to be acting directly at the site labelled by [3H]glibenclamide.
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PMID:Hypothermia induced by cholinomimetic drugs is blocked by galanin: possible involvement of ATP-sensitive K+ channels. 751 82

To study the responses of thermogenic activity in brown adipose tissue (BAT) to creatine depletion, male Wistar rats were fed creatine analogue beta-guanidinopropionic acid (beta-GPA) for about 10 weeks. Compared to control rats, a marked decrease in the levels of high-energy phosphates, such as phosphocreatine and ATP, was noted in BAT of beta-GPA rats. Conversely, upward trends in other chemical components (DNA, glycogen, and total protein) in BAT as well as an increase in BAT mass were observed in beta-GPA rats, suggesting a tendency to hyperplasia of the BAT. The thermogenic activity (which was assessed by guanosine 5'-diphosphate binding to BAT mitochondria) in the mitochondria recovered from BAT of beta-GPA rats, however, was not increased in response to such changes but rather decreased. Moreover, uncoupling protein (UCP) content in the mitochondrial fraction of beta-GPA rats was significantly lower than that in control rats (the relative amounts were 77 +/- 6 and 100 +/- 4%, respectively). Nevertheless, surprisingly, the level of UCP mRNA was remarkably greater in beta-GPA rats than in control rats. These observations indicate that there is a discordance between BAT growth and activity in beta-GPA rats, thereby suggesting that a failure on and after UCP translation may be involved in the impairment of BAT thermogenic activity with creatine depletion. The impairment of BAT thermogenic activity, that is, UCP activity may indicate that uncoupling or heat production was inhibited in order to increase the ATP synthesis in BAT of beta-GPA rats in compensation for a reduction in the levels of high-energy phosphates (including ATP), with resultant hypothermia.
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PMID:Increased growth of brown adipose tissue but its reduced thermogenic activity in creatine-depleted rats fed beta-guanidinopropionic acid. 761 43

The current study was undertaken so that the effects of both ischemia and ischemia + hypothermia could be examined in mammalian liver. Particular reference was made to the function of glycolysis, which is the only mechanism for energy production under these conditions. The response of adenylate pools reflected the energy imbalance created during warm ischemia within minutes of organ isolation. ATP levels and energy charge values for control (freshly isolated) livers were 1.20 +/- 0.07 and 0.49 +/- 0.02 mumol/g. Within 5 min of warm ischemia, ATP levels had dropped well below control values and by 30 min warm ischemia, ATP, AMP, and E.C. values were 0.21, 2.01, and 0.17 mumol/g, respectively. Cold ischemic livers (flushed with Marshall's citrate solution and stored on ice) exhibited similar, but more protracted, patterns of adenylate depletion (ATP and ADP) and accumulation (AMP). In both warm and cold ischemic livers, levels of fructose-6-phosphate (F6P) and fructose-1,6-bisphosphate (F1,6P2) indicated a marked activation of glycolysis at the phosphofructokinase (PFK) locus after a certain time of ischemia. Although the activations occurred at different times (30 min and 10 h for warm and cold ischemic livers, respectively), the patterns of change in levels of glycolytic metabolites associated with the PFK-catalyzed reaction were similar; levels of F6P dropped and F1,6P2 increased. Changes in metabolite levels (phosphoenol pyruvate and pyruvate) associated with another key suspect regulatory enzyme, pyruvate kinase, indicated no role in regulatory control of glycolysis during warm or cold ischemia. The activation of PFK at 30 min and 10 h of warm and cold ischemia, respectively, may reflect the accumulating effects of loss of intracellular homeostasis, which leads to impending irreversible damage.
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PMID:Glycolysis and energy metabolism in rat liver during warm and cold ischemia: evidence of an activation of the regulatory enzyme phosphofructokinase. 798 53

The purpose of this investigation was to examine the effect of oxygenated perfluorochemical perfusion on ischemia injury to skeletal muscle in rabbits. Forty-two hindlimbs of white rabbits were divided into six groups: 3-hr perfusion; 6-hr perfusion; 3-hr hypothermia; 6-hr hypothermia; sham operation without perfusion or hypothermia preservation; and biopsy. Endothelial cells in these muscles were evaluated using electron microphotography. The areas of both the inner and outer sides of cross-sectioned endothelial cells without cell nuclei were measured, and a new "capillary index" was calculated: (outer area--inner area)/outer area. The values of the capillary index in the perfusion groups were similar to those in the biopsy group. However, the values in the hypothermia groups were significantly greater than those in the biopsy group. These measurements suggested that the perfluorochemical perfusion method preserved the capillary endothelial cells in a nearly normal condition. The adenine nucleotides of these muscles were also evaluated. ATP levels in the 6-hr hypothermia group showed a substantial decrease to 57 percent of those in the sham-operated group. The 6-hr perfusion group levels, however, decreased only to 80 percent of those in the sham-operated group. Although application of the oxygenated perfluorochemical perfusion method did not maintain normal ATP levels, the maintenance of ATP levels was clearly higher than levels maintained in the hypothermia-preservation group. These findings suggest that oxygenated perfluorochemical perfusion is a satisfactory method for preserving amputated limbs.
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PMID:Morphologic and metabolic study of the effect of oxygenated perfluorochemical perfusion on amputated rabbit limbs. 807 6

The effects of cold and restraint and of some of the antiulcer drugs on adenosine nucleotide content in the gastric glandular mucosa were examined. A bioluminescence technique was used to measure the amount of ATP and its metabolites in gastric mucosal tissue. Cold-restraint produced gastric lesions and increased the gastric mucosal ATP. Verapamil pretreatment attenuated these lesions and further intensified the ATP increase in a dose-related manner. The ATP/ADP ratio and the Atkinson index were also elevated. Calcium gluconate produced similar effects. Atropine or EGTA pretreatment protected or worsened the gastric lesion, respectively, but did not have any influence on the changes in mucosal energy metabolism. Ranitidine pretreatment lessened the lesion formation but had no influence on the nucleotide content. These findings indicate that the metabolic rate of the gastric mucosa is suppressed during cold-restraint conditions; this depression is probably due to hypothermia and reduction of mucosal metabolism. The lesion-protecting mechanisms of the drugs do not seem to be mediated through their effects on mucosal energy metabolism. The oxygen- and ATP-sparing effects of verapamil may contribute partly to its gastro-protective effect.
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PMID:Role of gastric glandular mucosal energy metabolism in cold-restraint gastric lesion formation. 818 16


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