UMLS:C0022116 - FACTA Search

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Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravenous infusion of acetylstrophanthidin to 6 dogs, after a 60 min left anterior descending coronary artery occlusion, was associated with a 43.0 +/- 10.5% decrease in the dose of digitalis needed to produce ventricular arrhythmias as compared to the pre-ischemic dose (97.5 +/- 8.0 microgram/kg). Reperfusion of the ischemic region for 2 h after a 90 min occlusion resulted in a 54.4 +/- 6.7% decrease in the arrhythmogenic dose. Direct intracoronary infusions of digitalis into the ischemic region, after a 90 min coronary occlusion followed by 2 h of reperfusion, was associated with a 47.7 +/- 6.4% decrease in the dose of digitalis needed to produce arrhythmias. The pre-ischemic (control) arrhythmogenic dose of digitalis via the intracoronary infusion method was 1.5 +/- 0.3 microgram/kg (mean +/- S.E.M. of 7 dogs). Sodium pump activity, estimated from the ouabain-sensitive 86Rb uptake in sodium-loaded ventricular slices, was significantly higher in slices obtained from the ischemic regions (6.84 +/- 0.30 nmoles 86Rb/mg dry wt. (mean +/- S.E.M.), than from the non-ischemic regions (3.43 +/- 0.64 nmoles 86Rb/mg dry wt.). Sensitivity of the sodium pump activity to the inhibitory effect of ouabain also was increased in the ischemic regions as indicated by a shift in the log dose--response curve to the left. Thus, it appears that there is an increase in myocardial sensitivity to the toxic effect of digitalis after temporary ischemia and it appears to be related to an increase in the sensitivity of the Na+,K+-ATPase or sodium pump to the inhibitory effect of digitalis.
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PMID:Ischemic-induced alterations in cardiac sensitivity to digitalis. 48 58

Failure of the myocardium to take up Thallium-201 is widely used as a diagnostic marker for ischemia or infarction. Although this is commonly related to a reduction in coronary flow or myocardial perfusion, other possible metabolic factors are poorly understood. The present studies investigated the influence of various interventions, designed to simulate the metabolic consequences of ischemia, on thallium-204 uptake and release in cultured myocardial cells. In these cells, where thallium exchanged rapidly (t 1/2 = 5 min.), and 60% of thallium uptake occurred via the sodium pump, thallium uptake was markedly influence by changes in extracellular potassium. Increasing extracellular potassium from a physiologic level of 5 mM to those levels reported to occur in ischemic myocardium (7.5 mM to 18 mM) effected a 25% to 60% reduction in thallium influx. The decrease in thallium influx produced by increasing extracellular potassium was rapid (30 sec.) in onset and readily reversible by restoring extracellular potassium towards normal. Changes in extracellular pH in the range 6.4 to 8.0 had no demonstrable effect on thallium uptake despite the fact that this was accompanied by similar, although less marked, changes in intracellular pH. Addition of adenine nucleosides, adenosine, inosine and hypoxanthine, to the incubating solution in concentrations from 1 nM to 0.1 mM had no effect on thallium influx or efflux in the cells. This observation held true even when 10 microM dipyridamole was used to inhibit nucleoside uptake by the cells. Addition of 1 mM 2, 4-dinitrophenol or 4 mM potassium cyanide to the cultures maximally inhibited 42% of the thallium influx within 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of ischemia-related metabolic factors on thallium exchange in cultured rat myocardial cells. 242 79

The role of O2 free radicals in the reduction of sarcolemmal Na+-K+-ATPase, which occurs during reperfusion of ischemic heart, was examined in isolated guinea pig heart using exogenous scavengers of O2 radicals and an inhibitor of xanthine oxidase. Ischemia and reperfusion reduced Na+-K+-ATPase activity and specific [3H]ouabain binding to the enzyme in ventricular muscle homogenates and also markedly lowered sodium pump activity estimated from ouabain-sensitive 86Rb+ uptake by ventricular muscle slices. These effects of ischemia and reperfusion were prevented to various degrees by O2-radical scavengers, such as superoxide dismutase, catalase, dimethyl-sulfoxide, histidine, or vitamin E or by the xanthine oxidase inhibitor, allopurinol. The degree of protection afforded by these agents paralleled that of reduction in enhanced lipid peroxidation of myocardial tissue as estimated from malondialdehyde production. These results strongly suggest that O2 radicals play a crucial role in the injury to sarcolemmal Na+-K+-ATPase during reperfusion of ischemic heart.
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PMID:O2 free radicals: cause of ischemia-reperfusion injury to cardiac Na+-K+-ATPase. 302 76

Myocardial ischemia causes both systolic and diastolic dysfunction. A variety of positive inotropic agents with different subcellular mechanisms may be used clinically in an attempt to reverse ischemic contractile failure. We tested the hypothesis that two inotropic agents, isoproterenol (a beta-adrenergic agonist) and ouabain (a sodium pump inhibitor), might have different effects on left ventricular (LV) diastolic function during ischemic failure despite an equivalent inotropic effect. Isolated isovolumic (balloon-in-LV) blood perfused rabbit hearts were paced at constant physiological heart rate (4 Hz), given either no drug (controls, n = 7), isoproterenol (n = 7), or ouabain (n = 7), and then subjected to 6 minutes of low flow ischemia (75% reduction of baseline coronary flow). The doses of isoproterenol and ouabain were selected to produce equivalent modest inotropic effects (15% increase in LV + dP/dt) in each heart during baseline perfusion conditions. During the ischemic period, there was a marked decrease in contractility, and neither isoproterenol nor ouabain demonstrated a positive inotropic effect relative to the control group. However, these agents had markedly different effects on diastolic chamber distensibility (assessed by end-diastolic pressure at constant LV volume) during ischemia. In the control and isoproterenol groups, diastolic chamber distensibility did not change during the ischemic period. In contrast, ouabain treatment resulted in a marked decrease in diastolic chamber distensibility during ischemia; this change was not completely reversible during the 10-minute reperfusion period. The mechanism by which ouabain decreased diastolic chamber distensibility relative to isoproterenol was assessed indirectly. The ouabain and isoproterenol groups were subjected to equivalent degrees of ischemia as assessed by oxygen supply/demand imbalance; during ischemia, each drug group did not differ with regard to myocardial perfusion rates, determinants of myocardial oxygen demand (heart rate, LV developed pressure, LV + dP/dt), myocardial oxygen consumption, lactate production, and ATP and creatine phosphate content. We therefore inferred that the greater decrease in diastolic distensibility in the ouabain group was not due to a greater metabolic severity of ischemia. These observations are consistent with a mechanism of cytosolic calcium overload induced by ouabain, resulting in persistent active myofilament tension development throughout diastole, to cause the observed decrease in diastolic chamber distensibility during ischemia in the ouabain group.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of ouabain and isoproterenol on left ventricular diastolic function during low-flow ischemia in isolated, blood-perfused rabbit hearts. 339 61

The early stages of anoxemia and ischemia are associated with highly selective, reversible defects in sarcolemmal ionic exchange of potassium not necessarily the result of impaired sodium pump function. At a later stage structural defects in the membrane led to irreversible loss of intracellular potassium and creatine kinase. Similar stages can be demonstrated in the sarcolemmal selectivity for divalent cations. The degree of sarcolemmal injury from ischemia can be significantly influenced by the conditions of reperfusion. Reduced calcium content of blood reperfused for only 5 minutes can improve the mechanical recovery of ischemic rabbit ventricle. The influx of calcium during reperfusion impairs those processes required for restoration of sarcolemmal integrity.
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PMID:Myocardial ischemia: ionic events in ischemia and anoxia. 625 41

Digitalis sensitivity of the heart is increased in patients with ischemic heart disease. Whether this elevation of digitalis sensitivity occurs as the result of ischemia-induced changes in the cardiac tissue and whether changes in the sarcolemmal Na,K-adenosine triphosphatase (ATPase) or reserve capacity of the sodium pump are responsible for the increased digitalis sensitivity were examined using isolated heart preparations obtained from guinea pigs. Ligation of the left anterior descending coronary artery (LAD) in Langendorff preparations 40 min before perfusion with a toxic concentration (either 1.8 or 2.5 microM) of digoxin decreased the time to the onset of arrhythmias. LAD-ligation by itself did not cause arrhythmias. The time to the onset of arrhythmias during digoxin perfusion was slightly longer in preparations obtained from reserpine-treated animals; however, the reserpine pretreatment failed to alter the effect of LAD ligation on digitalis sensitivity, indicating that the release of catecholamines is not involved in the sensitization. The effects of ischemia on Na,K-ATPase and sodium pump activities, glycoside binding to the enzyme and reserve capacity of the sodium pump were examined in globally ischemic Langendorff preparations. The preparations were perfused with a Krebs-Henseleit bicarbonate buffer solution (pH 7.4) saturated with a 95% O2-5% CO2 gas mixture at a control flow rate of 2.5 ml/g of tissue per min or at 5 or 0% of the control flow rate. After 6 hr of zero perfusion, Na,K-ATPase activity and the number of specific ouabain binding sites were reduced in ventricular muscle homogenates. However, the remaining Na,K-ATPase was not altered in its sensitivity to dihydrodigoxin-induced inhibition or affinity of binding sites for ouabain, sodium or potassium. Similar results were observed after reperfusion following 2 or 5 hr of zero perfusion. A 5% perfusion for 2 or 6 hr, or zero perfusion for 2 hr failed to affect Na,K-ATPase activity in muscle homogenates. Sodium pump activity in ventricular slices, estimated from the ouabain-sensitive 86Rb+ uptake, was unchanged after 5% perfusion or zero perfusion for 2 hr, but was significantly reduced after a 20-min reperfusion following 2 hr of zero perfusion. Reserve capacity of the sodium pump, as estimated from the differences in 42K+ uptake by right ventricular strips under 1.5 and 7 Hz stimulation, was unaffected by 2 hr of 5% perfusion. These results indicate that coronary artery occlusion enhances the arrhythmogenic action of digitalis in isolated heart preparations. This change in digitalis sensitivity produced by 40 min of occlusion cannot be explained by reductions in Na,K-ATPase activity or sodium pump reserve capacity as 2 hr of zero perfusion does not alter Na,K-ATPase or sodium pump activity in ventricular tissue.
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PMID:Ischemia-induced enhancement of digitalis sensitivity in isolated guinea-pig heart. 630 6

Acute myocardial ischemia reduces tolerance of the heart to arrhythmogenic actions of digitalis glycosides. Because both ischemia and the glycoside produce profound changes in activity of the autonomic nervous system and because sympathetic discharge or catecholamines enhance toxic actions of the cardiac glycosides, the possibility that alterations in digitalis sensitivity of ischemic heart involve changes in sympathetic nerve activity was examined using alpha-chloralose-anesthetized cats. Left anterior descending coronary artery (LAD) was completely occluded by ligation and, 40 min later, a slow i.v. infusion of digoxin was started at a rate of 1 microgram/kg/min. LAD ligation alone did not produce arrhythmias in that condition, but shortened the time to onset of digoxin-induced arrhythmias and thereby reduced the amount of digoxin required to produce the toxic manifestation. Concomitantly, digoxin concentration in plasma and nonischemic areas of the heart were lower in LAD-ligated cats at the onset of arrhythmias than those in sham-operated cats. Myocardial digoxin content in the ischemic area of the LAD-occluded heart was lower than that in nonischemic areas of the same heart. At the onset of digoxin-induced arrhythmias, Na,K-adenosine triphosphatase activity of ischemic myocardium was significantly higher than that in the nonischemic area, reflecting a lower digoxin occupancy of the glycoside binding sites on the sodium pump. Spinal cord (C1) transection or propranolol treatment prolonged the time to arrhythmias in both control and LAD-ligated cats, but failed to abolish the effect of LAD ligation to augment digoxin toxicity. Bilateral vagotomy also did not alter the enhancement of digoxin toxicity caused by ligation of LAD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of sympathetic nervous system in ischemia-induced reduction of digoxin tolerance in anesthetized cats. 632 71

The timecourse of change of the cytoplasmic free energy of ATP hydrolysis during acute global ischemia and during anoxic perfusion was determined in the isolated rat heart. The timecourse of change of transsarcolemmal Na+ and K+ gradients during anoxia, and of extracellular K+ during ischemia were measured. The free energy of ATP hydrolysis was calculated from the equilibrium of the creatinekinase reaction, taking into account the pH-dependence of the equilibrium constant, and intracellular inorganic phosphate. In control aerobic hearts the mean free energy of ATP hydrolysis was 55.2 kJ/mol. Both during ischemia and anoxia it declines biphasically. The first rapid phase terminates within 4 min into a plateau of about 46 kJ/mol. The duration of this plateau is shorter during anoxia than during ischemia. The second phase of decrease starts after 6 to 8 min during anoxia and after 15 to 20 min during ischemia. After 30 min of anoxia the free energy of ATP hydrolysis has decreased to 31 kJ/mol and after 30 min of ischemia a value of 35.5 kJ/mol is reached. The timecourses of change of measured intracellular Na+ and K during anoxia and of extracellular K+ during ischemia were also biphasic. During anoxia the loss of intracellular K+ was almost equal to the gain of intracellular Na+ at any point. Based on the assumption that the sodium pump is in thermodynamic equilibrium or near-equilibrium during anoxia and ischemia, the time-course of change of Na+ and K+ gradients during anoxia and of extracellular K+ during ischemia were calculated from the respective timecourses of change of the free energy of ATP hydrolysis. Good agreement was observed between calculated and measured changes of Na+ and K+ gradients. It is concluded that the magnitude and direction of change of transsarcolemmal ion-gradients during anoxia and ischemia may be under direct thermodynamic control of myocardial energy metabolism.
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PMID:The change of the free energy of ATP hydrolysis during global ischemia and anoxia in the rat heart. Its possible role in the regulation of transsarcolemmal sodium and potassium gradients. 652 Aug 74

To determine the relative influence of two levels of ischemia on myocardial cation and water composition as well as cardiac function, intact anesthetized dogs were studied for 1 h using a balloon-tip catheter in the proximal left anterior descending coronary artery. Hemodynamic studies in group A revealed a diminished ejection fraction during mild and severe ischemia associated, respectively, with a 36% and 74% decline in transmural coronary flow. Left ventricular end diastolic pressure rose only after severe ischemia. Greater accumulation of sodium and water and loss of K+ in ischemic tissue was observed in animals with severe ischemia. In group B, intracellular cations and water were estimated on the basis of 51Cr-labeled EDTA distribution. The extracellular space was unaltered at either level of ischemia. During mild ischemia, cell Na+ and H2O were enhanced in the inner and outer layers of myocardium. Despite a 25% reduction in subendocardial blood flow by the labeled microsphere technique, K+ content was normal. After severe ischemia, cell K+ was reduced in inner and outer layers. However, the increase of cell Na+ content substantially exceeded K+, suggesting a major effect on the sodium pump or cell permeability.
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PMID:Dissociation of myocardial sodium and potassium alterations in mild versus severe ischemia. 737 31

Na+/K+ adenosinetriphosphatase (sodium pump) may play a key role in the prevention of reperfusion injury caused by Ca2+ overload. The present study was undertaken to investigate the role of sodium pump activity in warm induction of cardioplegia combined with reperfusion of oxygenated cardioplegic solution. Isolated and perfused rat hearts were subjected to 15 minutes of normothermic ischemia to produce a model of severely failing heart. The hearts then received myocardial preservation. Warm (37 degrees C) or cold (4 degrees C) oxygenated modified St. Thomas' Hospital solution was given for 5 minutes before and after 120 minutes of hypothermic cardioplegic arrest. Reduced myocardial pH during normothermic ischemia was adjusted toward the baseline level by administration of cold or warm oxygenated cardioplegic solution without a significant intergroup difference. Myocardial adenosine triphosphate levels decreased to less than 30% of the preischemic level during 15 minutes of normothermic ischemia, but were increased partly by induction of cold or warm oxygenated cardioplegia. Thus these metabolic indices failed to demonstrate the superiority of warm over cold oxygenated cardioplegia. Na+/K+ adenosinetriphosphatase activity in the membrane fraction was significantly stimulated by a cardioplegic dose of K+ with maximum activity at 16 mEq/L. The enzyme activity of the heart measured after normothermic ischemia was reduced to less than 50% of that in the nonischemic heart. Although warm induction of cardioplegia and reperfusion of oxygenated cardioplegic solution maintained Na+/K+ adenosinetriphosphatase activity at the preischemic level, the enzyme activity was abolished at 4 degrees C, which is the temperature used in cold cardioplegia. A subtoxic dose of ouabain (0.1 mmol/L) inhibited the enzyme activity of the heart undergoing this preservation regimen to approximately 50%. Warm induction and reperfusion of oxygenated cardioplegic solution showed significantly better recovery of isovolumic left ventricular function during reperfusion compared with that obtained with cold oxygenated cardioplegia. However, the beneficial effect of warm oxygenated cardioplegia on left ventricular function was compromised by inclusion of 0.1 mmol/L ouabain without a significant effect on myocardial metabolic parameters. These results suggest that stimulation of Na+ pump activity may account for the beneficial effect of warm induction and reperfusion of oxygenated cardioplegic solution in the energy-depleted heart.
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PMID:Role of sodium pump activity in warm induction of cardioplegia combined with reperfusion of oxygenated cardioplegic solution. 760 33

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