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

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

The ability of dl-verapamil to enhance myocardial protection when given before, during, or after myocardial ischemia was assessed with the use of an isolated working rat heart model of cardiopulmonary bypass and ischemic cardiac arrest. Under conditions of normothermic ischemic arrest (30 minutes at 37 degrees C), the addition of verapamil enhanced the protective properties of the St. Thomas' Hospital cardioplegic solution. Optimal protection was observed with verapamil concentrations of 0.5 mg/L (1.09 mumol/L) of cardioplegic solution. Under these conditions, postischemic enzyme leakage was reduced by 32.2% and the postischemic recovery of aortic flow was improved by 18.7%. Despite the additional protection at normothermia, the drug at several concentrations appeared unable to improve functional recovery after an extended period of hypothermic arrest (150 minutes at 20 degrees C), although under these conditions its inclusion in the cardioplegic solution could substantially reduce enzyme leakage. In other studies, the ability of various doses of verapamil alone as a substitute for the cardioplegic solution was examined. At the optimal dose (again 0.5 mg/L), and under normothermic conditions, verapamil alone was a good protection against ischemic injury, although this protection did not match that afforded by the St. Thomas' Hospital cardioplegic solution. In similar studies under hypothermic conditions, the drug failed to afford tissue protection, perhaps indicating some common modality between hypothermia and verapamil-induced protection. Pretreatment with verapamil (0.1 mg/L) prior to ischemia offered moderate additional protection, but its use during reperfusion failed to enhance overall recovery.
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PMID:Cardioplegia and slow calcium-channel blockers. Studies with verapamil. 687 61

Past studies have not established the optimal myocardial temperature range for hyperkalemic arrest but have generated controversy regarding the safety of exposing the myocardium to more profound levels of hypothermia. We therefore used the isolated working rat heart model of ischemic arrest to study the metabolic and functional effects of cardioplegia at the full range of temperatures pertinent clinically. Experimental conditions were designed to reliably control and maintain myocardial temperature during the 60 minute arrest period. We found that nearly full recovery of function occurred when hearts were arrested at or below 16 degrees C. High-energy phosphate levels measured immediately after arrest were better maintained at 4 degrees and 8 degrees C, despite evidence of decreased anaerobic glycolysis. When measured after the recovery period, high-energy phosphate levels returned to somewhat less than control levels in all groups arrested at or below 24 degrees C. Myocardial glucose utilization was best preserved in hearts arrested at or below 12 degrees C. We found no evidence that greater myocardial edema resulted from arrest at colder temperatures. Severe and permanent damage was observed when hearts were arrested at or above 28 degrees C. In this model, therefore, the best overall metabolic and functional protection occurred when hearts were maintained at 12 degrees C or below potassium-induced cardioplegia. Our results support the idea that cold injury to the heart does not occur and that colder temperatures provide better protection from ischemic myocardial injury.
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PMID:Effect of temperature during potassium arrest on myocardial metabolism and function. 709 10

The hypothesis tested was that the composition of the prime and the perfusate at the time of reperfusion had an influence on postischemic cardiac performance. Twelve dogs in two equal groups had long (210 +/- 10 minutes) hypothermic (25 degrees +/- 1 degree C) perfusions. Each had 180 minutes of global ischemia and were given 500 ml of the same cold (4 degrees C) cardioplegic solution (CPS) every 45 minutes and topical hypothermia with a resultant average myocardial temperature of 10 degrees +/- 2 degrees C. Group A had a prime (1,958 ml) consisting of a 50/50 mixture of 5% dextrose in water and 5% dextrose in Ringer's injection to which mannitol (12.5 gm), furosemide (20 mg), and heparin (6,000 units) were added. Group B received a prime (1,868 ml) of 5% dextrose in Ringer's injection (1 L) and 750 ml of 6% helastarch in normal saline to which NaHCO3 (10 mEq), furosemide (20 mg), mannitol (25 gm), and heparin (6,000 units) were added. During perfusion, Group A received lactated Ringer's solution and Group B received a 1 : 2 portions of Ringer's injection and 6% helastarch. Additionally, Group B received additional furosemide and mannitol 5 minutes prior to the reperfusion interval. The results showed a marked difference between groups in postischemic cardiac recovery 120 minutes after cessation of cardiopulmonary bypass. The Group B dogs had statistically (less than 0.02) greater cardiac output, stroke volumes, and stroke work index at equal preloads and lower total peripheral resistances. Arterial systolic, diastolic, and mean pressures and right atrial pressures were not different. The Group A dogs required nearly threefold the volume of fluid additions required during bypass and twice the amount of NaHCO3 as Group B dogs. It is concluded that the composition of the prime and fluids used during bypass and use of agents to counteract tissue water accumulation during the ischemic and reperfusion intervals strongly influences postischemic cardiac performance. Further, these data suggest that the composition of the perfusate may have a greater influence on the functional recovery of the heart than the composition of various CPSs.
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PMID:Adequacy of the perfusate: its influence on successful myocardial protection. 713 9

Oxygenated Fluosol-43 cardioplegia (CP), a perfluorocarbon with high oxygen solubility, was compared with crystalloid and oxygenated blood cardioplegia. Potassium in each CP was 25 mEq/l. Thirty perfused rabbit hearts in three groups of 10 hearts each underwent 100 minutes of global ischemia at 20 degrees C, followed by 45 minutes of reperfusion at 37 degrees C. During ischemia, CP was given every 20 minutes. With each CP injection, increases in myocardial oxygen tension were recorded using mass spectrometry and oxygen consumption (MVO2) was calculated. Left ventricular function was assessed before and after ischemia by measuring isovolumic developed pressure and dP/dt with an intraventricular balloon. Intramyocardial PO2 increased by 19.6 +/- 1.8 mm Hg in the Fluosol CP group, 0.4 +/- 0.1 mm Hg in the crystalloid CP group and 1.5 +/- 0.3 mm Hg in the blood CP group (p less than 0.001, Fluosol CP vs crystalloid CP and blood CP). MVO2 with each CP injection, expressed as ml O2/100 g dry weight, was 203.8 +/- 7.0 for Fluosol CP, 20.4 +/- 1.2 for crystalloid CP and 39.2 +/- 4.3 for blood CP (p less than 0.001 Fluosol CP vs crystalloid CP and blood CP). Recovery of maximal dP/dt after 45 minutes of reperfusion, expressed as a percentage of preischemic control, was 75.6 +/- 4.0% for Fluosol CP, 60.9 +/- 5.5% for crystalloid CP and 53.4 +/- 3.7% for blood CP (p less than 0.02 Fluosol CP vs blood CP and crystalloid CP). These data clearly show that the use of Fluosol cardioplegic solution enhanced oxygen delivery and use compared with blood and crystalloid cardioplegic solutions. The marked increase in intramyocardial oxygen and MVO2 with each injection of Fluosol CP shows that there is effective aerobic metabolic activity during ischemia, which may explain the improved functional recovery. The failure of blood CP to afford similar protection can be explained by a decreased oxygen release from hemoglobin due to the leftward shift of the oxygen-hemoglobin dissociation curve with hypothermia.
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PMID:Superiority of perfluorocarbon cardioplegia over blood or crystalloid cardioplegia. 724 32

In a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest the potential additive protective effects of hypothermia and chemical cardioplegia have been investigated. Isolated rat hearts were subjected to a 2 minute period of coronary infusion with a cardioplegic or a noncardioplegic solution immediately before and also at the midpoint of a 2 hour period of hypothermic (20 degrees C) ischemic cardiac arrest. In the hypothermia plus cardioplegia group postischemic aortic flow recovered to more than 50% of its preischemic control value, myocardial energy phosphate content returned to near preischemic control levels, and creatine kinase leakage was moderate. By contrast, in the hypothermia alone group (coronary infusion with non cardioplegic solution) the postischemic functional recovery was less than 30% of its preischemic control value, cellular high-energy phosphate content was considerably reduced, and creatine kinase leakage was more than twice that observed in the hypothermia plus cardioplegia group. In addition to illustrating the additive nature and powerful protective properties of hypothermia and cardioplegia these studies serve to illustrate the utility of the isolated rat heart model for the primary assessment of procedures designed to protect the myocardium during ischemic cardiac arrest. The results and conclusions derived from this study were quantitatively and qualitatively similar to those obtained in a parallel study in the dog.
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PMID:The additive protective effects of hypothermia and chemical cardioplegia during ischemic cardiac arrest in the rat. 735 Mar 87

A new myocardial support system has been developed and a study of this system is reported. Cardioplegia was induced by continuous infusion of potent "cardioplegic" agents (potassium chloride and potassium chloride with propranolol) at the aortic root in 12 dogs subjected to cardiopulmonary bypass with total body hypothermia (20 degrees C). A low-flow normal-pressure perfusion was maintained with the aid of a norepinephrine drip. During the period of hypothermia the blood pH was maintained at 7.6 and serum magnesium concentration was increased to an average of 2.1 mmol/l by parenteral infusion of magnesium sulfate. At no time was ischemia induced and the aorta was not cross-clamped. The functional recovery to normal and preservation of the ultrastructure of the subendocardium after 4 hours of perfusion in cardioplegia were remarkable. The control hearts from hypothermic dogs that were allowed to fibrillate spontaneously showed severe damage.
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PMID:Perfusion in cardioplegia: an experimental study. 736 75

The preponderance of studies of tolerance to organophosphate (OP) cholinesterase (ChE) inhibitors indicates that functional recovery accompanies neurochemical compensations for the inhibited enzyme. Contrary to prediction, rats dosed with the OP diisopropylfluorophosphate (DFP) showed progressive and persistent impairment of cognitive and motor function over a 3-week period of daily exposure, despite neurochemical and pharmacological evidence of tolerance to its inhibition of ChE. To determine whether these functional effects of DFP resulted from inhibition of ChE and downregulation of muscarinic cholinergic receptors, rats were dosed with chlorpyrifos (CPF), an OP pesticide which inhibits blood and brain ChE of rats for weeks after a single injection. Long-Evans rats were trained to perform an appetitive test of memory and motor function and were then injected s.c. with 0, 60, 125 or 250 mg/kg of CPF in peanut oil and tested 5 days/week for 7 weeks. Unconditioned behavior was also rated for signs of cholinergic toxicity. CPF inhibited ChE activity in whole blood in a dose-related manner for more than 53 days. The degree and time course of ChE inhibition in blood and brain and the downregulation of muscarinic receptors in brain after 125 mg/kg of CPF closely paralleled the previously reported effects of 25 daily injections of 0.2 mg/kg of DFP. In addition, CPF-treated rats were subsensitive to oxotremorine-induced hypothermia for at least 32 days after CPF. However, functional deficits (in working memory and motor function) appeared within 2 days after injection of CPF and recovered within 3 weeks, long before ChE activity and receptor density returned to control levels. Thus, the effects of CPF were neither progressive nor as persistent as those seen during daily DFP injections. This difference suggests that the DFP-induced behavioral changes observed previously cannot be attributed entirely to its effects on ChE activity and changes in [3H]quinuclidinyl benzilate binding.
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PMID:Behavioral and neurochemical effects of acute chlorpyrifos in rats: tolerance to prolonged inhibition of cholinesterase. 768 99

Aspartate and glutamate each have been shown to improve cardiac recovery after hypoxia or ischemia under normothermic conditions, but whether their effects are additive and to what extent they are modified by hypothermia has not been studied systematically. We set out to compare the individual and combined protective effects of aspartate and glutamate during cardioplegic arrest under normothermic and hypothermic conditions in the rat. Using isolated working rat hearts, functional and metabolic recovery was assessed after 0.5 hours of potassium arrest at 37 degrees C or 5 hours at 2 degrees C in control hearts (C) and in hearts in which 20 mmol/L glutamate (G), 20 mmol/L aspartate (A), or both (A + G) was added to the cardioplegic solution. Under normothermic conditions, percentage recovery of prearrest work (mean +/- standard error of the mean) was as follows: C = 31.7 +/- 2.8, G = 34.8 +/- 0.2, A = 49.6 +/- 2.8*, A + G = 53.7 +/- 2.3*. Under hypothermic conditions, the values were as follows: C = 40.4 +/- 4.0, G = 45.2 +/- 2.3, A = 59.4 +/- 1.8*, A + G = 54.1 +/- 1.2* (*p < 0.01 versus C and G). Recovery of postischemic high-energy phosphate content followed the same pattern: A = A + G > G or C. Measurement of postischemic myocardial content of amino acids showed that recovery of function and energy status correlated with maintenance of myocardial levels of aspartate (r = 0.9; p < 0.01) but not glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differing protection with aspartate and glutamate cardioplegia in the isolated rat heart. 777 37

Experimental observations in our laboratory indicate that myocardial recovery is similar following warm or cold antegrade blood cardioplegia when the core temperature is maintained at 37 degrees C. To determine the effects of hypothermia on myocardial recovery, 15 adult mongrel dogs were randomized to normothermic or hypothermic bypass (28 degrees C) during 60 min of continuous warm antegrade blood cardioplegia. The hypothermic group was rewarmed after releasing the aortic cross-clamp and bypass was discontinued at 30 min in both groups. Myocardial recovery was assessed at 60, 90, and 120 min after the arrest. Core temperature was maintained in the normothermic group but gradually decreased after bypass in the hypothermic group, reaching a low of 33.8 +/- 1 degrees C at 120 min. Myocardial functional recovery was preserved after normothermic bypass. The decrease in core temperature, however, that was observed after systemic hypothermia, was paralleled by significant decreases in the maximum rate of left ventricular pressure rise (dp/dt), the maximum elastance of the left ventricle, and preload recruitable stroke work. Diastolic function decreased slightly, but not significantly, during reperfusion following systemic hypothermia but was unaltered after normothermic bypass. Myocardial oxygen consumption was unchanged in both groups. Myocardial ultrastructure was preserved after normothermic bypass. In contrast, cellular oedema and mild ultrastructural changes were evident after systemic hypothermia. We therefore conclude that the use of systemic hypothermia during bypass is associated with lower core temperatures during early recovery which results in impaired functional recovery.
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PMID:Influence of systemic hypothermia on systolic and diastolic functional recovery after continuous warm antegrade blood cardioplegia. 781 84


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