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

Insertion of a flow pump into the Langendorff retrograde perfusion apparatus has permitted the production of stable, graded ischemia in hearts whose hemodynamic and metabolic response may be evaluated. Ventricular pressures were monitored with a modified balloon and catheter-tip manometer system, and oxygen consumption , lactate and glucose metabolism, and tissue high-energy phosphate stores measured. A 15-min stabilization period in 56 paced hearts was followed by 15 min of either full, 40, 30, 20, or 10% coronary flow, after which the ventricular tissue was freeze-clamped for tissue assay. Tissue creatine phosphate fell progressively from 23.7 in full flow hearts to 9.9 mumol/g dry wt after 90% reduction in flow. This was accompanied by a graded reduction in ATP from 20.3 to 14.0 mumol/g dry wt and a rise in AMP from 1.1 to 2.6 mumol/g dry wt. Tissue lactate rose progressively from 22.3 to 60.1 mumol/g dry wt. Hemodynamic function correlated with coronary flow. This preparation offers an opportunity to study pharmacological and metabolic interventions in ischemic heart disease.
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PMID:A model of graded ischemia in the isolated perfused rat heart. 93 18

The selective metabolic effects of glucose and insulin were tested in an intact working swine heart preparation. Supplements of glucose (26.6 millimolar [mM] and insulin (0.025 units/ml) were provided to 18 hearts, 9 control hearts (coronary flow 151 ml/min) and 9 hearts rendered globally ischemic (coronary flow reduced from 167 to 85 ml/min). These hearts were compared with 14 additional hearts (6 control and 8 ischemic) given no supplements (glucose 8.6 mM, no excess insulin). In hearts without supplements, ischemic significantly decreased mechanical performance, myocardial oxygen consumption, fatty acid oxidation and tissue high energy phosphate stores. Glucose consumption was reduced from 133 micromoles (mumol)/hr per g (before ischemia) to 58 mumol/hr per g (P less than 0.05), presumably from inhibition at glyceraldehyde-3-phosphate dehydrogenase. Data for control hearts with excess glucose and insulin were similar to data in control hearts without supplements except that glucose consumption and glycolytic flux were increased. Ischemia in treated hearts, as compared with untreated ischemic hearts, effected similar significant decreases in myocardial oxygen consumption, fatty acid oxidation and high energy phosphate stores and resulted in greater reductions in mechanical performance and in 10 minutes' less average survival time. Glucose consumption was reduced from 483 (before ischemia) to 242 mumol/hr per g (P less than 0.005) and inhibition at glyceraldehyde-3-phosphate dehydrogenase was again noted. Thus, excess carbohydrate and insulin hormone, when infused directly into the ischemic myocardium, did not provide an efficacious increase in either glycolytic flux or energy production. These findings suggest that an alternative explanation for the reported efficacy of glucose-insulin-potassium infusions must be sought.
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PMID:Effects of excess glucose and insulin on glycolytic metabolism during experimental myocardial ischemia. 93 98

An isolated perfused working rat heart model was used to investigate the extent to which various protective agents, used either singly or in combination, were able to increase the resistance of the heart to periods of transient ischemia. The aim of the studies was to develop a solution which, if infused into the coronary vessels just prior to the onset of ischemia, would rapidly induce arrest and would also counteract several of the deleterious cellular changes known to occur during myocardial ischemia. Agents with induce cardiac arrest, modify cellular ion loss, affect substrate utilization, energy production and energy stores, affect coronary vessel diameter and cell swelling, prevent dysrhythmias, and affect metabolic rate were investigated. The additive effects of these agents were evaluated. An aqueous solution was formulated which contained high concentrations of potassium and magnesium, in combination with adenosine triphosphate, creatine phosphate and procaine. This solution increased the recovery of the ischemic (37 degrees C for 30 min) rat heart from 0% to 93%. The safe period of ischemia could be further increased by the use of hypothermia.
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PMID:Cellular protection during myocardial ischemia: the development and characterization of a procedure for the induction of reversible ischemic arrest. 93 20

Failure of glycolysis to increase sufficiently to supply optimal levels of energy production in ischemic heart muscle is due in part to the cummulative restrainst of acidosis on rate-limiting enzymes, particularly glyceraldehyde-3-phosphate dehydrogenase. In an effort to modify this inhibition and salvage jeopardized myocardium, treatment with excess levels of pyruvate and tromethamine (Tris), designed to buffer intracellular hydrogen ion accumulations and improve the oxidation-reduction ratio, NAD+/NADH, was tested in 59 swine hearts in two separate preparations of global and regional ischemia. Global ischemia, per se, caused hemodynamic deterioration and shortened survival time (44.3 +/- 3.1 minutes). Myocardial oxygen consumption, fatty acid oxidation, and glucose uptake were all significantly (P less than 0.001) reduced as were estimates of glycolysis and tissue stores of creatine phosphate and ATP (P less than 0.01). Although treatment with Tris alone was inconclusive, administrations of pyruvate (40-50 mM) buffered with Tris (added directly into the coronary perfusate) effected an improvement in mechanical function and a significant prolongation in survival time (56.9 +/- 2.6 minutes. P less than 0.01). Glycogenolysis was enhanced and levels of key glycolytic intermediates were reduced, suggesting an acceleration of glycolytic flux. Excess levels of pyruvate (1.52 +/- 0.48 mumol/ml of coronary perfusate) provided added substrate for oxidation and led to a greater than 5-fold incrase in rates of pyruvate decarboxylation as compared to untreated ischemic hearts...
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PMID:Effects of treatment with pyruvate and tromethamine in experimental myocardial ischemia. 95 68

A possible protective effect of glucocorticoids on the ischemic myocardium was investigated in in situ dog hearts subjected to regional ischemia and in isolated rat hearts subjected to global ischemia. In the whole-animal preparation, the left anterior descending coronary artery (LAD) was occluded for 3 hours, or for 2 1/2 hours followed by 30 minutes of reperfusion. Dexamethasone phosphate was randomly administered (20 mg. per kilogram intravenously) after 15 minutes of ischemia. Its effects were studied on the following: (1) myocardial cell membrane integrity, using electron microscopic examination of tissue biopsies treated with colloidal lanthanum; (2) myocardial water content, measuring the wet/dry weight of myocardial tissue; (3) ischemic injury, by a count of fuchsinophilic cells at light microscopy. In isolated rat hearts, ischemia was produced by a 60 per cent reduction of coronary flow. Randomized hearts were perfused for 2 hours with dexamethasone, 15 mg. per milliliter in buffered salt solution. Study included determination of tissue water content and coronary vascular resistance. Lanthanum was confined to the extracellular spaces in normal dog myocardium, but it was found all intracellularly after 3 hours of ischemia or after reperfusion. This was associated with morphologic changes characteristic of irreversible cell injury. In the hearts treated with dexamethasone, lanthanum remained excluded from the cells, water content was less (p less than 0.005), and fuchsinophilia less severe (p less than 0.005). Likewise, water content was less (p less than 0.005) and the increase in coronary vascular resistance resulting from ischemia less severe (p less than 0.005) in the dexamethasone-treated isolated rat hearts. Thus dexamethasone administered in pharmacologic doses, early, appeared to stabilize the cell membrane, limit myocardial edema, and reduce the severity of injury, both during ischemia and upon reperfusion.
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PMID:Glucocorticoid protection of the myocardial cell membrane and the reduction of edema in experimental acute myocardial ischemia. 96 99

We evaluated hyperthermic influences on ischemic hearts by comparing two groups of intact working swine hearts (n = 20) made globally ischemic. Heart muscle temperature was selectively increased from 37.5 +/- 0.3 degrees C to 39.7 +/- 0.3 degrees C in one group (n = 11) by warming the coronary perfusate. Ischemia in normothermic hearts significantly (P less than 0.05) decreased mechanical function (as reflected by increases in left ventricular end-diastolic pressure [LVEDP]), myocardial oxygen consumption (MVO2), glucose uptake, glycolytic flux, free fatty acid (FFA) uptake and oxidation, and tissue stores of high energy phosphates. Hearing in ischemic hearts further depressed mechanical function at similar reductions in coronary flow and MVO2. Glucose uptake was terminally increased over normothermic values (329 vs. 221 mumol/hr per g) as was glycolytic metabolism, FFA uptake (26 vs. 17 mumol/hr per g), and FFA oxidation (21 vs. 11 mumol/hr per g). However, these changes were not translated into increased energy stores of tissue creatine phosphate and ATP. Thus, in ischemic hearts, hyperthermia neither prevented the development of mechanical deterioration nor improved oxidative phosphorylation despite increases in metabolic substrate utilization. These data suggest that in experimental global ischemia heat is an added energy drain in already burdened myocardium.
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PMID:Effects of hyperthermic stress on myocardial function during experimental coronary ischemia. 97 53

This study determines the effect of ischemia and reperfusion on energy-linked Ca2+ uptake by myocardial mitochondria. The left anterior descending coronary artery was occluded in 14 mature pigs for 2 hr. In seven animals the ligature was released and the ischemic zone reperfused for 2 additional hours. After sacrifice, mitochondrial function was measured in normal and reperfused or ischemic areas of the left ventricle, using a polarographic method. Mitochondria were prepared without EDTA by standard procedures and Ca2+ uptake measured by 45Ca2+ isotope tracer. Uptake of Ca2+ by mitochondria derived from ischemic myocardium is markedly impaired with or without phosphate. Reperfusion may accentuate this impairment. The presence of exogenous Ca2+ inhibits the ability of ischemic or reperfused mitochondria to phosphorylate ADP.
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PMID:Alteration in calcium metabolism in mitochondria isolated from ischemic and reperfused myocardium. 103 50

The perfused rat heart was used to assess the possible contribution of glycolytically produced ATP to the maintenance of the action potential in the normoxic heart, and to the maintenance of membrane integrity in the underperfused, ischemic heart. During normoxia, pyruvate (10 mM) was nearly as able as glucose (10 mM) to maintain the normal action potential. During ischemia (reduction of perfusion pressure of Langerdorff heart from 100 to 20 cm H2O), total tissue values of ATP and creatine phosphate were similar in pyruvate and in glucose hearts. However, pyruvate-perfused hearts had higher tissue levels of cyclic AMP during the ischemic period, and during the reperfusion period they had an increased release of lactate dehydrogenase and an increased incidence of arrhythmias when compared with glucose hearts. It is proposed that these differences can be related to a higher rate of production of glycolytic ATP. The anatomical, biochemical, and pharmacological evidence favoring a cytoplasmic compartment of ATP located in relation to the cell membrane is reviewed.
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PMID:Glycolytic ATP and its production during ischemia in isolated Langendorff-perfused rat hearts. 103 48

With a polysaccharide microsphere suspension (Sephadex), coronary flow of isolated perfused rat hearts was reduced by approximately 70%. During this Sephadex-induced ischemia, the energy charge and creatine phosphate content of the myocardial tissue dropped significantly, while total nucleoside and lactate release from the heart increased. During hypoxia (30% O2), changes in high-energy phosphate content and lactate and nucleoside release were similar to the changes induced by ischemia. During hypoxia, coronary flow rate was increased by 47%. Thus, Sephadex-induced reduction of coronary flow could be a useful model in studies of metabolic change during ischemia.
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PMID:Metabolic consequences of Sephadex-induced reduction of coronary flow in isolated rat heart. 103 79

Pacing-induced myocardial ischemia in 18 patients resulted in an increase of coronary sinus hypoxanthine levels from 1.20 +/- 0.18 micron during control to 2.41 +/- 0.52 micron (p less than 0.025) during pain. In addition, early lactate production occurred frequently before angina was noted. Neither hypoxanthine nor lactate levels changed in seven nonanginal patients, nor were significant alterations in potassium, inorganic phosphate, glucose, or oxygen saturation found in all patients. Myocardial hypoxanthine production seems a useful indicator of ischemia in the human heart.
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PMID:Changes in purine nucleoside content in human myocardial efflux during pacing-induced ischemia. 103 94


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