Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of quinacrine on malondialdehyde (MDA) as an index of lipid peroxidation, activities of phospholipase A2 (PLA2), and myeloperoxidase (MPO)--a neutrophil granulocyte maker in plasma--was examined in rats following ischemia and reperfusion. In the absence of quinacrine, ischemia and reperfusion caused increased MDA content and increased activities of PLA2 and myeloperoxidase in the plasma. All these effects were efficiently inhibited by the PLA2 inhibitor quinacrine. The finding indicates that the occurrence of an increased level of MDA following intestinal ischemia may be used for diagnostic purposes and points to the possibility that high plasma MDA might indicate a need for PLA2 inhibitor treatment.
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PMID:Influence of quinacrine on plasma malondialdehyde after small intestinal ischemia and reperfusion. 283 Sep 96

Superimposition of cardioplegic arrest on acute low-cardiac-output states, as may occur after failure of percutaneous transluminal coronary angioplasty requiring emergency surgery, is associated with an increased operative risk. This increased risk is possibly attributable to reperfusion, which, after sequential episodes of myocardial ischemia, exacerbates tissue injury mediated by oxygen free radicals. One of the most cytotoxic of these active oxygen species is the hydroxyl radical, which is formed from superoxide anion and hydrogen peroxide through an iron-catalyzed reaction. This study assesses the effects of peroxidase, a hydrogen-peroxide scavenger, and of deferoxamine, an iron chelator, in isolated working rat hearts subjected to 30 minutes of low-flow ischemia (75% reduction in coronary flow) followed by 2 hours of cardioplegic arrest at 15 degrees C and by 30 minutes of normothermic reperfusion. Three groups of hearts (n = 7) were studied. Two groups were pretreated with either peroxidase (10,000 units/l) or deferoxamine (0.03 mM) during the last 15 minutes of the low-flow ischemic period. The third group received no prearrest intervention and served as a control group. In addition to hemodynamic determination, high-energy phosphate content [adenosine 5'-triphosphate (ATP)] and intracellular pH were monitored serially by 31P nuclear magnetic resonance spectroscopy. The two pretreated groups had better recovery of ATP levels and aortic flow values than did the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardioplegic arrest superimposed on evolving myocardial ischemia. Improved recovery after inhibition of hydroxyl radical generation by peroxidase or deferoxamine. A 31P nuclear resonance study. 284 3

This study investigates the action of intravenous PGE1 on myocardial reperfusion injury and the possible involvement of antineutrophil activities. Cats were subjected to 3 h of temporary ligation of the left anterior descending coronary artery, followed by 2 h of reperfusion. Animals were treated with PGE1 (5 micrograms/kg x min) or vehicle (saline solution), starting 0.5 h after coronary artery occlusion. Vehicle-treated cats exhibited a significant loss of cardiac creatine phosphokinase specific activity at 5 h, accompanied by a significant ischemia-induced rise in the ST segment of the ECG and development of a Q wave after starting reperfusion. All of these alterations were largely prevented by PGE1 treatment. PGE1 exerted some blood-pressure-lowering activity at 5 h (P greater than 0.05) but did not reduce myocardial contractile force and oxygen consumption. PGE1 modestly antagonized ischemia-induced formation of platelet aggregates. However, PGE1 prevented the rise in peripheral white blood cell count during ischemia and reperfusion and inhibited the generation of reactive oxygen species (myeloperoxidase assay) from zymosan-stimulated whole blood ex vivo. The ratio of generation of reactive oxygen species/white blood count remained unchanged. It is concluded that PGE1 protects the ischemic myocardium from acute reperfusion injury and that this effect involves an action of the compound on neutrophils, probably by improved myocardial tissue preservation, resulting in reduced formation of chemotactic products and, consequently, less local neutrophil accumulation and release of noxious metabolites.
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PMID:Protection of the ischemic myocardium from reperfusion injury by prostaglandin E1 inhibition of ischemia-induced neutrophil activation. 284 5

If myocardial ischemia always results from an imbalance between the needs and supplies in oxygen of the myocardium cells, the physiopathology of this process seems today infinitely more complex than the mere diminution or interruption of the output in a coronary artery. The extension of atheromatous lesions, the platelets aggregation, thrombosis, the coronary spasm, the release of products from the arachidonic cascade, the reactivity of the vascular endothelium, the profibrinolytic activity of the tissues are many of the intricate factors inducing myocardial ischemia. Cellular alterations, of which some are triggered by the release of oxygenated free radicals, lead then to an irreversible necrosis. The medications used until now in the treatment of angina are oxygen scavengers and research goes on in this direction with vaso-dilators beta-blockers, prolonged action nitro-compounds (nicorandil) or nitro-compounds with an action reinforced by N-acetyl-cysteine, bradycardiac derivates of alinidine and the new calcium antagonists dihydropyridine. However, the new physiopathological concepts of ischemia have opened new directions for the research: products which modify the arachidonic cascade by increase of synthesis or release of PGI2 (nafazatrom, defibrotide), by inhibition of TXA2 synthesis or blocking of TXA2 receptors, and similar products of PGI2 (iloprost); thrombolytic agents more specific of thrombin (PTA) or fibrinolysis activators (defibrotide), and anticoagulants with extended action; chelating agents of oxygenated free radicals (peroxide dismutase, catalase, peroxidase) or xanthine oxidase inhibitors; platelets anti-aggregates like ticlopidine which blocks the platelets receptors to fibrinogen, or inhibitors of the synthesis of pro-aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Current therapeutic concepts in the treatment of myocardial ischemia. Current and future drugs]. 287 4

A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radicals may mediate the microvascular and parenchymal injury produced by reperfusion of ischemic skeletal muscle. One potential source of these reactive oxygen metabolites is the inflammatory neutrophil. To assess neutrophil accumulation in postischemic skeletal muscle, we measured tissue myeloperoxidase (MPO) activity in skeletal muscle biopsies taken during control, after 4 h of ischemia, and after 1 h of reperfusion. Tissue levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were measured in the same samples to identify alterations in tissue free radical defense mechanisms due to ischemia-reperfusion. Reperfusion of ischemic skeletal muscle was associated with a dramatic increase in tissue neutrophil content (as reflected by a 26-fold increase over control in tissue MPO activity after 1 h of reperfusion) and a concurrent 50% decrease in GSH content. Tissue CAT and SOD activities were unaffected by ischemia-reperfusion. These results suggest a possible relationship between ischemia-reperfusion-induced injury, neutrophil infiltration, and the reduction in tissue GSH.
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PMID:Free radical defense mechanisms and neutrophil infiltration in postischemic skeletal muscle. 292 39

Effects of ischemia on cell membrane of rat heart were investigated. The endothelial surface revealed the existence of ruthenium red-positive glycocalyx at the anionic site. Membrane bound enzyme as Na-K ATPase was mostly located in the inner side and pinocytotic vesicles of endothelial cell. The clumping and dispersion in glycocalyx of endothelial cells was observed in an ischemic heart and it may prove the functional disturbance of plasma membrane. A potential and functional defect with reduced activity of Na-K ATPase occurred within 1 hr of vascular ligation. The membrane dysfunction due to these molecular changes has been proved by the membrane permeability alteration as well as the intracytoplasmic localization of horseradish peroxidase as tracer.
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PMID:Early membrane damage during ischemia in rat heart. 300 26

Oxygen-derived free radicals play an important role in the myocardial injury associated with ischemia and reperfusion. This study was designed to assess whether the protection afforded by a K+ rich, Mg2+ rich cardioplegic solution could be enhanced by the addition of free radical scavengers acting at different levels of the radical generating pathway. Forty isolated isovolumic rat hearts were divided into five groups (n = 8). Four groups of hearts were subjected to 90 minutes of normothermic cardioplegic arrest followed by 45 minutes of reperfusion. Hearts were given an initial bolus of either unmodified cardioplegic solution or cardioplegic solution enriched with superoxide dismutase (200,000 U/L) reduced glutathione (0.1 mmol/L), or peroxidase (6,000 U/L). One group of hearts was aerobically perfused throughout the experimental protocol and served as nonischemic controls. Based on comparisons of postreperfusion ventricular pressure development, maximal ventricular dP/dt, left ventricular compliance and coronary flow, peroxidase-containing cardioplegic solution afforded the best myocardial protection, with values of these indicators not significantly different from those of nonischemic perfused control heart. Glutathione afforded protection slightly inferior to that of peroxidase but still markedly better than in groups receiving superoxide dismutase or unmodified cardioplegic solution. This study confirms that cardioplegic protection can be enhanced by the addition of free radical scavengers, in particular peroxidase.
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PMID:A comparative study of free radical scavengers in cardioplegic solutions. Improved protection with peroxidase. 301 15

This study assesses the ability of the free-radical scavenger peroxidase to enhance cardioplegic protection when given during or before myocardial ischemia. Forty-four isolated isovolumetric buffer-perfused rat hearts were studied. In a first series of experiments that consisted of three groups, hearts were subjected to 90 min of normothermic global ischemia followed by 45 min of reperfusion. One group received a crystalloid cardioplegic solution given as a single dose at the onset of arrest. A second group received cardioplegic solution supplemented with superoxide dismutase (200,000 U/liter), and a third group received cardioplegic solution supplemented with peroxidase (6000 U/liter). Based on comparisons of postreperfusion coronary flow, left ventricular developed pressure, maximum dP/dt, and diastolic pressure, we found that the best protection was provided by peroxidase-enriched cardioplegia. A second series of experiments was then undertaken to assess the effects of the latter enzyme given as a pretreatment. Hearts were subjected to 3 hr of global ischemia, during which myocardial protection was provided by hypothermia (15 degrees C) along with multidose cardioplegia. The treatment group was given peroxidase (10,000 U/liter) added to the perfusate fluid for 15 min before the onset of cardioplegic arrest without further enzyme supplementation during ischemia or reperfusion. Hearts perfused with standard buffer for an equal period of time served as controls. While the two groups demonstrated the same degree of postischemic increase in myocardial stiffness, peroxidase-pretreated hearts had a significantly better recovery of contractile indexes at 30 and 45 min of reflow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhancement of cardioplegic protection with the free-radical scavenger peroxidase. 302 57

Platelets are suggested to exacerbate ischemia-induced myocardial injury, which has led to the study of various antiplatelet therapies including thromboxane synthetase inhibitors (TXSI). Two such agents, benzylimidazole and OKY-046, reduce infarct size commensurate with a diminution in serum thromboxane B2 formation in anesthetized dogs subjected to 90 minutes of coronary artery occlusion followed by 5 hours of reperfusion. In contrast, platelet depletion with specific antiserum does not reduce infarct size but prevents the cardioprotection afforded by the TXSI. Platelet-derived prostaglandin endoperoxides (PGG2 and PGH2), which cannot be converted to thromboxane A2 in the inhibited platelet, can be transformed to PGE2 and PGD2 in plasma and to PGI2 by the blood vessel wall. These prostaglandins are considered "cardioprotective." Consequently, a low dose of aspirin (3-5 mg/kg) given 24 hours before coronary occlusion was used to selectively block the platelet cyclooxygenase enzyme. Aspirin, by itself, does not reduce infarct size, but it suppresses the myocardial salvage induced by OKY-046. Thus, TXSI reduce infarct size by platelet-dependent, aspirin-sensitive mechanism that depends on the redirection of platelet-derived PGG2 and PGH2 to protective metabolites, rather than inhibition of thromboxane A2 per se. Moreover, myocardial salvage induced by the TXSI is accompanied by a reduction in neutrophil accumulation in the myocardium, as indicated by the levels of the neutrophil-specific myeloperoxidase enzyme. Platelet depletion or pretreatment with aspirin prevents the TXSI-induced suppression of neutrophil accumulation. Consequently, it is proposed that the prostaglandin-mediated protective effects of TXSI can be resolved, at least in part, in terms of a braking action on neutrophil activation to prevent leukocyte-dependent tissue injury.
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PMID:Thromboxane synthetase inhibitors reduce infarct size by a platelet-dependent, aspirin-sensitive mechanism. 312 73

Cultured heart cells have been shown useful for investigating states of oxygen and volume restrictions, simulating anoxia and ischemia-like states at cellular levels. The sarcolemma has been implicated as one of the early sites of ischemic damage; therefore, lactoperoxidase catalyzed radioiodination was used to study accessibility of the sarcolemmal lipid moieties to this enzymatic probe, reflecting their exposure to the extracellular environment, hence the biophysical state of the sarcolemma. These studies have shown that within one hour of 'ischemic' injuries: (1) The degree of labelling in the total phospholipid fraction is considerably increased; and (2) Profound changes in the relative extent of labelling of different phospholipid classes were observed. The PE/PC labelling ratio increases dramatically with the progress of ischemia-like state. We suggest that early during ischemic injury, reorganization of the cell surface phospholipids occurs and discuss possible relations to the energy charge of the cell.
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PMID:Studies on oxygen and volume restriction in cultured cardiac cell: possible rearrangement of sarcolemmal lipid moieties during anoxia and ischemia-like states. 337 78


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