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

The pathogenesis of the calcium paradox has not been established. In calcium-free perfused hearts, caffeine, which releases calcium from the sarcoplasmic reticulum, causes severe myocardial injury, with creatine kinase (CK) release and contraction band necrosis similar in many respects to the calcium paradox. It has been postulated that contracture, initiated by a small rise in intracellular calcium, may cause sarcolemmal injury in both the calcium paradox and caffeine-induced myocardial injury. The present study was initiated to determine whether interventions which modulate caffeine-induced contracture will also correspondingly alter cellular injury. The effects of caffeine dose, procaine, extended calcium-free perfusion, elevated potassium, temperature, and increasing intracellular sodium on caffeine-induced contracture were examined in Langendorff-perfused adult rat hearts. Caffeine-induced contracture at 22 C increased over a dose range of 5-40 mM caffeine. Procaine, which inhibits caffeine-induced calcium release at doses between 5 and 20 mM, progressively reduced contracture caused by addition of 20 mM caffeine at 22 C. Hearts perfused with calcium-free solution containing 16 mM K+ showed a reduction in caffeine-induced contracture. Extended calcium-free perfusion (20 minutes) at temperatures from 18 to 37 C resulted in a progressive reduction of caffeine-induced contracture. Each of these interventions was also found to inhibit caffeine-induced injury at 37 C. Low temperature was found to have complex effects. Hypothermia enhanced caffeine contractures but also protected hearts from cell separations and CK release. Increasing intracellular sodium was found to enhance caffeine-induced contracture at 37 C. There was a direct correlation between measured intracellular sodium levels and the magnitude and duration of caffeine-induced contracture. These results demonstrate a direct correlation between the magnitude of contracture and myocardial injury in calcium-free hearts. It is proposed that contracture is the primary mediator of sarcolemmal membrane injury in hearts with intercalated disks weakened by prior calcium-free perfusion.
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PMID:Modification of caffeine-induced injury in Ca2+-free perfused rat hearts. Relationship to the calcium paradox. 370 96

An isolated working rat heart preparation was used to characterise the temperature-dependency of the anti-ischaemic properties of nifedipine. In this study hearts were subjected to pre-ischaemic infusion with the St Thomas' cardioplegic solution with or without added nifedipine (0.075 mumol X litre-1). Hearts were then rendered globally ischaemic for various periods, (35, 42, 48, 56, 55, 65, 80, 105 or 130 min) at various temperatures (37.0, 35.5, 34.0, 32.5, 31.0, 29.0, 27.0, 24.0 or 20.0 degrees C, respectively). The duration of ischaemia at each temperature was selected to produce a post-ischaemic (37 degrees C) recovery of aortic flow that was approximately 50% of its pre-ischaemic (37 degrees C) control. In addition to functional indices (aortic flow, cardiac output, coronary flow, aortic pressure and heart rate) creatine kinase leakage during reperfusion was measured. At all temperatures at or above 31 degrees C the addition of nifedipine enhanced significantly (maximal value = 43%) the post-ischaemic recovery of aortic flow and other indices of pump function, while at the same time reducing significantly (by up to 56%) enzyme leakage. At ischaemic temperatures below 31 degrees C nifedipine failed to afford any significant additional protection when assessed functionally or enzymatically. It would therefore appear that hypothermia either blocks the action of nifedipine or, by acting on some common mechanism, renders the actions of the drug redundant.
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PMID:Temperature-dependency of nifedipine as a protective agent during cardioplegia in the rat. 397 70

The efficacy of moderate hypothermia with rewarming in attenuating the myocardial and circulatory consequences of acute coronary ligation was studied in open-chest, anesthetized dogs. Thirty minutes after ligation of the proximal left anterior descending coronary artery, 14 dogs were surface-cooled to 27 degrees C, maintained at this temperature for 2 hr, rewarmed to normothermic levels, and monitored for an additional hour. Fifteen dogs were maintained for a corresponding time period after coronary ligation at normothermic levels. Dogs maintained normothermic demonstrated significant depression (from preligation values) of dP/dt, cardiac output (CO), stroke volume (SV), and left ventricular stroke work and power (LVSW, LVSP) at elevated levels of left ventricular end-diastolic pressure (LVEDP). Dogs subjected to the hypothermic procedure demonstrated decreased inotropic status during hypothermia, but with rewarming, exhibited significantly greater values of left ventricular pressure, dP/dt, CO, SV, LVSW, and LVSP at lower values of LVEDP than observed in dogs maintained normothermic. Increased dysrhythmic activity was not observed during hypothermia. Hearts from dogs subjected to the hypothermic protocol demonstrated qualitatively greater dehydrogenase activity both at the periphery and in the center of the nonperfused region. The results suggest that moderate hypothermia during evolving myocardial infarction may preserve left ventricular cardio- and hemodynamics and thus may be useful in delaying morphological and functional deterioration until definitive treatment can be instituted.
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PMID:Salutary effects of moderate hypothermia on the circulatory and myocardial consequences of acute coronary occlusion in dogs. 407 11

This study was undertaken to assess the effects of hypothermia and chemical cardioplegia on the functional recovery of hypertrophied non-failing rat hearts subjected to an extended period of global ischaemia. Left ventricular hypertrophy was produced by constriction of the abdominal aorta. Hearts were studied an average of 8 weeks following this procedure. Sham-operated animals served as controls. Twenty-nine isolated isovolumic perfused rat heart preparations were then subjected to 2 h of ischaemic arrest at 15-18 degrees C followed by 45 min of normothermic reperfusion. In one series of hearts (8 sham, 8 hypertrophied), myocardial protection consisted of hypothermia alone. In another series (6 sham, 7 hypertrophied), repeated infusions of cardioplegic solution at 30-min intervals throughout arrest were added to hypothermia. Hypothermia alone resulted in a similar preservation of contractility as evidenced by the recovery of dp/dtmax/left ventricular (LV) systolic pressure after 45 min of reperfusion (91.6 +/- 5.9% of control values in sham vs 78.6 +/- 6.5% in hypertrophied hearts). Conversely, the recovery of compliance was much more impaired in hypertrophied hearts as indicated by a significantly higher percentage of increase in post-ischaemic LV diastolic pressure (DP) (at 45 min of reperfusion: 243.8 +/- 27.5% of control values vs 167.1 +/- 23.8% in sham, P less than 0.05). The addition of cardioplegia improved the preservation of contractility in both groups but its major effect was to normalize the recovery of compliance in hypertrophied hearts so that post-ischaemic LVDP values were no longer different from those recorded in normal hearts (at 45 min of reperfusion: 102.1 +/- 32.8% vs 98.5 +/- 14.2% of pre-ischaemic values respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effects of cardioplegia on diastolic function of hypertrophied rat hearts after hypothermic ischaemic arrest. 624

The development of myocardial ischemia is known to elicit the formation and enlargement of collateral vessels. The stimulus for these events is unknown. We have investigated the possibility that cardiac tissue releases a factor that can stimulate endothelial cell proliferation. Hearts from New Zealand rabbits were made progressively ischemic by differential hypothermia. Extracts from these hearts were tested for their growth-stimulating ability and were found to increase the proliferation of fetal bovine aortic endothelial cells as well as DNA synthesis by 3T3 cells. The level of activity in the extracts appears to be related to the degree of ischemia as measured by creatine phosphokinase levels. The liberation of an endothelial cell growth factor by ischemic cardiac tissue may function in the initiation and/or potentiation of coronary collateral formation.
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PMID:Do ischemic hearts stimulate endothelial cell growth? 646 72

Phosphorus-31 nuclear magnetic resonance (31P NMR) can estimate tissue intracellular pH as well as the content of high-energy phosphate metabolites in isolated perfused hearts. We used 31P NMR to examine mechanisms associated with the recovery of ventricular function in hearts subjected to global ischemia and reperfusion, with special emphasis on intracellular pH, a previously unreported variable. Single-dose and multiple-dose administration of a hyperkalemic cardioplegic solution were compared with hypothermia alone in 18 isolated perfused rabbit hearts. Hearts in group 1 were subjected to 24 degrees C hypothermia during 60 minutes of global ischemia; group 2 hearts received a single injection of 37-mM KCL cardioplegic solution at 10 degrees C at the onset of ischemia; and group 3 hearts received a similar initial cardioplegic injection followed by two subsequent 24 degrees C injections at 20-minute intervals during the ischemic period. Using an intraventricular balloon, maximal dP/dt provided a quantitative index of left ventricular performance before and after ischemia. Return of ventricular function expressed as a percentage of control was 54 +/- 11% for group 1, 84 +/- 6% for group 2, and 101 +/- 18% for group 3. Differences in the rate of development of intracellular acidosis were noted during the 60-minute ischemic period. Intracellular pH fell to 6.09 +/- 0.12 in group 1, 6.31 +/- 0.09 in group 2, an 6.79 +/- 0.03 in group 3. In all three groups intracellular pH returned to control (pH 7.20) within 10 minutes of reflow. The metabolic correlates of functional recovery appeared to be the tissue content of ATP at the end of ischemia and after reflow. ATP content at the end of ischemia was 22 +/- 2% of control in group 1 hearts, 31 +/- 4% in group 2 and 64 +/- 2% in group 3. After 45 minutes of reperfusion, ATP levels recovered to 33 +/- 9% of control in group 1, to 71 +/- 9% in group 2 and to 86 +/- 6% in group 3. Although there were no differences between groups in the content of creatine phosphate after 60 minutes of ischemia, the rates of creatine phosphate decline were dissimilar. Further, during the early reflow period, a marked overshoot in tissue creatine phosphate was detected, especially in groups 1 and 2. Histologic damage assessed by light microscopy correlated with the metabolic data, confirming that multidose cardioplegia provided the best preservation of cellular morphology. These results demonstrate that the magnitude of intracellular acidosis and the associated increase in inorganic phosphate correlate inversely with recovery of postischemic ventricular structure and function. ATP, but not creatine phosphate, content correlates with return of contractile performance after reperfusion. The overshoot in creatine phosphate during early reperfusion might impede optimal restoration of ATP content and, as a result, optimal recovery of cell functions.
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PMID:Mechanisms of ischemic myocardial cell damage assessed by phosphorus-31 nuclear magnetic resonance. 679 21

An isolated rat heart preparation was used to characterize the temperature dependence of the calcium paradox and also to assess the validity of various indices of hypothermic protection. Hearts were subjected to 10-min periods of calcium depletion at various degrees of hypothermia followed by 20 min of normothermic calcium repletion. Using enzyme or protein leakage during calcium repletion as an index of hypothermic protection during calcium depletion, paradox injury was reduced extensively by relatively moderate hypothermia. Thus, depletion at 29 degrees C reduced total creatine kinase leakage by 57 +/- 4% from 1585 +/- 24 IU/g dry wt to 677 +/- 63 IU/g dry wt and at 25 degrees C leakage was reduced by 85 +/- 4% from 1585 +/- 24 IU/g dry wt to 237 +/- 71 IU/g dry wt. However, upon calcium repletion there was no recovery of contractile function. It was not until the myocardial depletion temperature was reduced to 20 degrees C that some functional recovery occurred. Under these circumstances cumulative creatine kinase leakage was reduced to below 88 IU/g dry wt, 6% of its normothermic value and protein leakage was undetectable. Functional recovery was not complete until the temperature was reduced to 15 degrees C or below. Correlation of cumulative enzyme leakage with functional recovery suggested a narrow release threshold (50 to 100 IU/g dry wt) above which no recovery occurred and below which a full recovery could be confidently predicted. Morphological assessments an all-or-none phenomenon; thus although increasingly severe hypothermia progressively reduced the percent of cells that sustained damage (as opposed to the degree of damage in all cells), it was not until 100% of cells appeared ultrastructurally undamaged that functional recovery was observed. Calcium-free perfusion at 4 degrees C protected the intercalated discs from gross lesions and prevented the separation of the external lamina from the surface coat. Our results also stress the heterogeneity of tissue injury and hypothermic protection and in addition shed further light upon the component mechanisms contributing to calcium injury.
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PMID:The temperature dependence of the calcium paradox: enzymatic, functional and morphological correlates of cellular injury. 687 88

Hearts preserved for 2 hours at 15 degrees C were evaluated for maximum function with the use of an isolated working dog heart subjected to stress. We determined left ventricular function by controlling aortic flow resistance and flow into the left atrium. Groups studied were hypothermia alone (H), hypothermia with a modified extracellular solution (H + DKS), hypothermia with a modified Collins solution (H + C), six periods of 20 minutes of hypoxic hypothermia followed by 10 minutes of blood reperfusion (H20 + R10) and blood cardiplegia (BC). Hypothermia alone for 1 hour was also evaluated. Functions were studied for 2 1/2 hours following reperfusion by determining Starling's curves for each heart. Our data show that H alone gave adequate myocardial protection for only 1 hour but not for 2 hours. H20 + R10 was better than H, but function was depressed. Use of H + C provided protection equal to H20 + R10, but the hearts recovered function slowly. Only hearts preserved by H + DKS and BC for 2 hours had normal function. Hearts from all groups except H + DKS and BC became edematous. Excellent function was obtained with DKS or BC following 2 hours of ischemia at 15 degrees C. Initial clinical use of BC supported these laboratory findings.
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PMID:Left ventricular function after preserving the heart for 2 hours at 15 degrees C. 736 42

The effects of ischemic arrest and reperfusion on isovolumic end-diastolic pressure, diastolic pressure-volume curves, and indices of ventricular relaxation and contractility were studied in an isolated feline heart preparation. In hearts subjected to 60 min of normothermic (37 degrees C) ischemic arrest, isovolumic developed pressure, and dP/dtmax during reperfusion returned to only approximately 60% of prearrest control levels. Isovolumic end-diastolic pressure (Ped) increased 37.0 +/- 4.3 mmHg and the time constant of ventricular relaxation was prolonged. Hearts maintained at 27 degrees C hypothermia during the 60-min ischemic period demonstrated improved contractile performance (approximately 100% of control), less elevation of Ped (21.4 +/- 4.5 mmHg), and no significant increase in the time constant of relaxation. In both groups of hearts, postarrest end-diastolic pressure-volume curves were shifted up and to the left, whereas indices of ventricular stiffness and muscle stiffness remained unchanged. These data suggest that the rise in isovolumic end-diastolic pressure observed after 1 h of ischemic arrest and reperfusion is the result of an upward and to the left shift of the entire diastolic pressure-volume relationship of the left ventricle. This shift does not appear to be related to diminished contractile performance or incomplete relaxation. Furthermore, the shift is not due to a change in muscle compliance, but to a reduction in the unstressed volume of the ventricle, which most likely results from myocardial contracture and edema.
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PMID:Mechanism of elevated left ventricular end-diastolic pressure after ischemic arrest and reperfusion. 746 24

We tested the ability of various cardiac preservation techniques to preserve left ventricular function of isolated canine hearts using preservation temperatures of 4 degrees or 15 degrees C. The four techniques tested were: (1) topical hypothermia, and hypothermic arrest induced by (2) perfusion of 1 liter of a modified Collins solution, (3) perfusion of 1 liter of a modified extracellular solution (DKS), or (4) perfusion of 500 ml of blood cardioplegia. Following the cold ischemia period, the hearts were reperfused with blood in the working heart preparation and tested for their ability to recover left ventricular function. Hearts preserved 2 hours at 15 degrees C using hypothermia, modified Collins solution, or DKS solution achieved an average of 60, 73, and 95%, respectively, of baseline function. Hearts preserved 3 hours at 4 degrees C using topical hypothermia attained 70% of baseline function, while hearts stored 5 hours at 4 degrees C using modified Collins solution or DKS solution recovered 83 and 92%, respectively, of baseline function. Hearts preserved at 4 degrees C functioned at levels equal to or greater than that of hearts stored at 15 degrees C, even though the hearts preserved at 4 degrees C were stored for longer periods than those preserved at 15 degrees C. Hearts preserved with blood cardioplegia for 2 hours at either 4 degrees or 15 degrees C achieved functions statistically the same as baseline levels during the reperfusion period. These data show no advantage for preservation temperatures of 15 degrees C compared with 4 degrees C. Our data provide a firm experimental basis for the clinical use of myocardial preservation temperatures of 4 degrees C, especially when combined with cardioplegia.
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PMID:Improved myocardial preservation at 4 degrees C. 746 74


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