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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bifunctional intramyocardial potassium ion (K+)-sensitive and bipolar wire electrodes were used to evaluate extracellular K+ dynamics and electrophysiologic changes during acute myocardial ischemia in the border zone, ischemic zone (5 to 7 mm from the border), central ischemic zone (15 to 25 mm from the border) and normal myocardium in 11 open chest dogs during a 30 min ligation of the left anterior descending coronary artery. At the end of this period, the hearts were injected with rhodamine dye and quickly frozen. Ultraviolet NADH (nicotinamide adenine dinucleotide) rhodamine fluorescence photography was used to localize the border between normally perfused and ischemic tissue and determine the site of electrodes in relation to this border. Before coronary ligation, extracellular K+ ranged from 4.0 +/- 0.3 to 4.3 +/- 0.3 mM in these four zones. After ligation, extracellular K+ accumulated in the ischemic and central ischemic zones in a pattern characterized by an initial rapid increase for approximately 5 min, followed by a slowly rising plateau phase, reaching maximal levels of 9.8 +/- 2.0 and 14.4 +/- 4.4 mM, respectively. In contrast, K+ dynamics in the border zone showed a biphasic response, with an initial rapid increase to a maximal level of 7.5 +/- 2.4 mM at approximately 9 min after coronary ligation, followed by a gradual decrease to a level of 5.3 +/- 1.2 mM by the end of the 30 min ligation period. No significant changes in K+ occurred in the normal zone throughout the ischemic period. The correlation of K+ electrode, electrophysiologic and postmortem NADH-rhodamine fluorescence data indicated the existence of a well defined border zone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Extracellular potassium dynamics in the border zone during acute myocardial ischemia in a canine model. 333 83

As one of the cause of acute myocardial ischemia, coronary vasospasm has attracted attention increasingly in clinical cardiology. We developed animal model of coronary vasospasm associated with transient myocardial ischemia by administration of histamine or serotonin in atherosclerotic miniature swine. Early systolic dysfunction as well as subendocardial NADH production of the ischemic region occurred within 10 sec after coronary occlusion, but ST segment started to elevate around 30 sec after occlusion in the isolated rat heart. As the important determinant factors of myocardial infarct size, the preocclusive perfusion area as well as collateral flow area could be measured quantitatively by use of double isotopes autoradiograms, and the close correlation was found between the salvaged area and collateral flow area in dogs. An importance of advancement in basic cardiology and development of new research techniques have been emphasized.
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PMID:Myocardial ischemia. 396 58

Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibilities: (a) dissociation of intramitochondrial electron support system and altered phospholipid integrity with inactivation of cytochrome oxidase, which results in release of ubisemiquinone, flavoprotein and superoxide radicals; (b) accumulation and increased release of intra/extracellular metabolites like NADH, lactate flavoproteins and catecholamines which react either with themselves or with O2 and ascorbic acid; (c) interaction of the metabolic product hypoxanthine with O2 in the presence of xanthine oxidase and (d) activation of phospholipase by calcium influx with enhanced arachidonic acid metabolism and superoxide radical production. Detailed in vitro radiobiological studies [4] have demonstrated that free radical reactions occur even at very low O2 tensions (83% of maximum rate of PO2 approximately 6 mmHg and 50% at PO2 approximately 1 mmHg), and Smith [5] has demonstrated that free radical peroxidation takes place quite rapidly in rat brain homogenates incubated in gas mixtures containing only 5% O2. Thus, the low oxygen tensions in ischemic tissue are adequate to support free radical reactions. The free radicals thus produced may initiate and enhance lipid peroxidation by attacking polyunsaturated membrane lipids.
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PMID:Production of free radicals and lipid peroxides in early experimental myocardial ischemia. 631 60

Isolated perfused heart preparations provide controlled conditions for the study of myocardial respiration and metabolism. Most studies utilize a hemoglobin-free perfusate which requires high arterial oxygen tension and high coronary perfusion rate. A blood-perfused rabbit heart preparation using an "assist" rabbit to maintain blood homeostasis has been developed which is suitable for respiratory, metabolic, and spectroscopic studies of myocardial function under controlled conditions. Fluorescence emission of reduced nicotinamide adenine dinucleotide (NADH) from the surface of blood-perfused rabbit heart was photographed to delineate areas of myocardial ischemia detectable as NADH fluorescence from reduced mitochondria. Blood reperfusion of ischemic myocardium resulted in disappearance of NADH fluorescence. Reocclusion of the coronary artery resulted in the same pattern and amplitude of NADH fluorescence.
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PMID:Delineation of myocardial ischemia in an isolated blood-perfused rabbit heart preparation. 648 21

Because myocardial ischemia is correlated with both an elevation of intracellular levels of amphiphilic lipid metabolites and a decrease in the rotenone-insensitive NADH cytochrome c reductase (RINCR), we investigated the effects in vitro of some amphiphilic lipid metabolites and synthetic detergents on the activity of RINCR-enriched subfractions of microsomes from isolated cardiac myocytes. RINCR activity was unaffected in vitro by the addition of lysophosphatidylethanolamine (up to 0.5 mM) but was inhibited (maximum 63%) by lysophosphatidylcholine (8 microM). Palmitoyl carnitine (up to 2 mM) was ineffective, but the coenzyme A thioesters of palmitate, stearate, oleate, and arachidonate were inhibitory at concentrations (less than 3 microM) below their critical micellar concentrations. Arachidonyl CoA was approximately one order of magnitude more inhibitory than the other long-chain acyl CoA thioesters. Kinetic analyses revealed the effect of arachidonyl CoA on RINCR activity to be exclusively an alteration of the Vmax with no change in the Km for cytochrome c. The inhibition of myocytic RINCR activity by long-chain acyl CoA may be unrelated to the bulk-phase detergency of this lipid amphiphile since the effects were observed at concentrations below the critical micellar concentration, and other lipid amphiphiles had no effect on RINCR activity. Inhibition of microsomal RINCR activity may result from localized disruption of the membrane microenvironment of the enzyme complex by penetration or dissolution of long-chain acyl CoA into the membrane. The pronounced sensitivity of myocytic RINCR activity to long-chain acyl CoA suggests a relationship between the decreased RINCR activity and the increased levels of this class of lipid metabolites observed in the ischemic myocardium.
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PMID:Inhibition of myocardial rotenone-insensitive NADH cytochrome c reductase by amphiphilic compounds. 650 37

The activity of a new antianginal drug, nonachlazine, synthetized in the Institute of Pharmacology, Academy of Medical Sciences of the USSR, has been demonstrated using model myocardial ischemias on anesthetized dogs and conscious cats. Antianginal activity was evaluated by ECG, epicardial electrogram, lactate level, and lactate/pyruvate ratio in the venous blood flowing from the ischemic myocardial area. The study of the cardiotropic effect of nonachlazine provided the following findings: (1) nonachlazine enhances ino- and chronotropic functions of the heart via stimulation of its beta-adrenergic receptors; (2) nonachlazine's positive chronotropic effect is substantially less marked than the inotropic one; (3) nonachlazine decreases the intensity of chronotropic reactions of the heart induced by isopreterenol. Biochemical analysis showed that in addition to its activation of oxidative phosphorylation, the ability of nonachlazine to stimulate glycogenolysis is also of importance in the development of its antianginal effect. This conclusion has been suggested by the following: (1) in acute myocardial ischemia, nonachlazine decreased lactate level and increased ATP level up to the norm; (2) at day 3 after ligation of the coronary artery, nonachlazine did not change lactate content, increased ATP and NAD, and decreased NADH2; (3) in experiments on rabbit myocardial mitochondria in vivo and in vitro nonachlazine was found to stimulate oxidative phosphorylation; (4) nonachlazine was found capable of increasing the norepinephrine level and of increasing phosphorylase a activity and the rate of glycogenolysis.
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PMID:On the mechanism of action of the antianginal drug nonachlazine on ischemic myocardium. 685 82

The effects of myocardial ischemia and reperfusion on pyruvate dehydrogenase (PDH) activity were studied in isolated rat hearts. PDH remained largely (80%) in the active form during 10 min of whole heart ischemia in hearts receiving 11 mM glucose as substrate. With reperfusion, PDH was converted to the inactive form (45% by 2 min) and then returned slowly to control levels. Addition of pyruvate (10 mM) to the glucose containing perfusate during reperfusion prevent the reperfusion inactivation of PDH (96% active). The maintenance of a high percent of PDH in the active form during ischemia occurred in spite of high mitochondrial ratios of NADH/NAD and acetyl CoA/CoA and was related to a very low mitochondrial ATP/ADP ratio. The low ATP and high ADP would restrict PDH kinase phosphorylation and inactivation of PDH during ischemia. Reperfusion resulted in a rapid increase in mitochondrial ATP/ADP ratio and the increased availability of ATP as substrate for the kinase coupled with continued high levels of NADH and acetyl CoA which stimulate kinase activity may have accounted for the early inactivation of PDH with reperfusion. Addition of pyruvate to the perfusate probably inhibited the PDH kinase and prevent the reperfusion inactivation of PDH.
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PMID:Effects of ischemia and reperfusion on pyruvate dehydrogenase activity in isolated rat hearts. 687 85

The influence of hyaluronidase (H) on subacute experimental myocardial ischemia was studied in isolated perfused rabbit hearts. Changes in ischemic area were assessed by epicardial nicotinamide adenine dinucleotide (NADH) fluorescence photography, an intrinsic high-resolution display of myocardial ischemia. Computerized determination of ischemic area was made from standardized photographs. Hyaluronidase was begun 20 minutes after coronary artery occlusion at 4 units/ml perfusate. NADH fluorophotographs were taken at 10-minute intervals up to 60 minutes of ischemia. Coronary sinus oxygen tension (PcsO2), myocardial oxygen consumption (MVO2), and coronary flow were determined. After 70 minutes, the hearts were perfused with rhodamine solution to identify areas of myocardial perfusion. In 13 H-treated hearts 54.3% +/- 3.7% (mean +/- SEM) of the nonperfused area (rhodamine stained) was ischemic (NADH fluorescent). In 14 untreated hearts 79.8% +/- 3.2% of the nonperfused area was ischemic (p less than 0.0001) and the ischemic areas were uniform. The distance between perfused and ischemic tissue was 952 +/- 78 micrometers in the H hearts and 504 +/- 35 micrometers in the untreated heart (p less than 0.0001). In the H hearts PcsO2 increased to 155% of the post-ligation control while it decreased to 79% in the untreated hearts (p less than 0.0001). MVO2 decreased in the H-treated hearts to 62%; the untreated hearts had no further change. In the H-treated hearts, coronary flow increased to 146% of the post-ligation control while it fell to 91% in the untreated group (p less than 0.0001). We conclude that H increases coronary flow while decreasing MVO2 during subacute ischemia. In H-treated hearts, significant amounts of myocardium remain normoxic within the nonperfused areas, and may potentially be salvaged after prolonged myocardial ischemia.
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PMID:Mechanism of action of hyaluronidase in decreasing myocardial ischemia post coronary occlusion in the isolated perfused rabbit heart. 711 92

Although platelets have been associated with angina pectoris, myocardial infarction, and sudden death, the platelet's capacity for induction and propagation of cardiac ischemia remains incompletely defined. We therefore evaluated the effects of platelet activation occurring within the coronary circulation and tested the hypothesis that inhibition of platelet function would prevent platelet-induced cardiac ischemia. Human platelets were isolated from blood obtained from normal donors by Sepharose 2B column chromatography, resuspended in Hepes buffer, and added to the perfusate of a Langendorff rabbit heart (platelet counts greater than 10,000/microliters). Without, and with low dose (10 microM) prostaglandin E1 (PGE1), a reversible inhibitor of platelet function, immediate and irreversible global cardiac ischemia, as monitored by NADH fluorescent photography, ensued (N = 4) following platelet activation with thrombin (0.1 to 1 U/ml). Higher concentrations of PGE1 (0.1 to 1 mM, N = 2) or aspirin ingestion (1000 mg taken approximately 12, 4, and 1 hr prior to experiment, N = 2) completely prevented this platelet-induced myocardial ischemia. Aspirin, unlike PGE1, was effective despite its inability to block thrombin-induced platelet aggregation in our in vitro gel-filtered system. We conclude that activation of platelets within the coronary circulation is sufficient for induction of irreversible cardiac ischemia. The efficacy of aspirin, a cyclooxygenase inhibitor, further suggests that the products of arachidonate metabolism (e.g., thromboxanes) have a fundamental role in the genesis of platelet-mediated myocardial ischemia.
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PMID:Platelet-mediated cardiac ischemia. 713 26

The character and extent of the myocardial ischemic "borderzone" was assessed in the rabbit, dog, pig, and monkey. A fluorophotographic technique permitting high resolution (+/- 50 micrometers) display of myocardial ischemia has been developed. Reduced intracellular NADH (ischemia) fluoresces and may be photographed while oxidized NAD (perfused tissue) does not. A coronary artery was ligated for 5 min in open-chest rabbits, dogs, pigs, and monkeys. A fluorescent dye was injected into the left atrium as a coronary vascular marker, and the tissue was quick-frozen. The ischemic margin was well seen and was jagged in all species. The distance from anoxic to perfused tissue (borderzone) was less than 50 micrometers in all species. A narrow "oxygen-diffusion zone" of nonperfused non-anoxic tissue is visible in isolated heart perfused with blood-free solution. The width of this zone is inversely related to myocardial oxygen consumption and is less than 50 micrometers in a working blood-perfused heart. We have not yet correlated the oxygen diffusion zone with the clinically defined salvageable borderzone. In dogs, collateral vessels provide a heterogeneous border to the ischemic region so that the canine ischemic pattern differs from that of pigs, rabbits, and monkeys.
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PMID:Early ischemia after complete coronary ligation in the rabbit, dog, pig, and monkey. 727 Jul 7


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