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

Clinical and experimental evidence for important interactions between platelets and vascular endothelium under conditions of myocardial ischemia is briefly summarized. The clinical evidence for a role of platelets in myocardial ischemia includes studies indicating alterations in platelet behavior and the therapeutic benefit of some antiplatelet drugs. Experimental evidence suggesting the importance of platelets in ischemia includes reductions in transmyocardial platelet number under these conditions, the cyclical reductions in coronary blood flow that result from intermittent intravascular platelet aggregation, and the relationship between induced platelet aggregation and cardiac arrhythmias. Evidence strongly suggesting the importance of platelet emboli and thromboxane generation as a major cause of reperfusion-induced ventricular arrhythmias is outlined.
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PMID:Pathophysiology of myocardial ischemia: importance of platelet-vessel wall interactions. 315 92

There is a growing body of evidence for the role of free radicals in mediating myocardial tissue injury during myocardial ischemia and in particular during the phase of myocardial reoxygenation. Associated with myocardial ischemia and reperfusion is the generation of oxygen-derived free radicals from a variety of sources that include the mitochondrial electron transport chain; the biosynthesis of prostaglandins; the enzyme xanthine oxidase; and circulating elements in the blood, with the polymorphonuclear neutrophil assuming a primary focus of attention. Experimental studies have shown that free radical scavengers (e.g., N-[2-mercaptopropionyl]glycine) and enzymes that scavenge or degrade reactive species of oxygen (superoxide dismutase or catalase) can reduce the mass of myocardial tissue that undergoes irreversible injury. Additionally allopurinol, which inhibits the enzyme xanthine oxidase, reduces ultimate infarct size, putatively by reducing the xanthine oxidase generation of superoxide anion. Neutrophils that enter the ischemically injured myocardium under the influence of chemotactic attraction and activation of the complement system generate and release highly reactive and cytotoxic oxygen derivatives that are destructive to the vascular endothelium and to the cardiac myocytes. Studies have documented that neutrophil depletion or suppression of neutrophil function (ibuprofen, nafazatrom, BW 755C, or more recently with prostacyclin or iloprost) results in a significant salvage of myocardial tissue that is subjected to a period of regional ischemia followed by reperfusion. Our current understanding of the events associated with myocardial ischemia suggests that within the ischemic myocardial region or area at risk, there is a population of cells that are reversibly injured and that reperfusion within a specified period (less than 3 hours) of time is capable of restoring the majority of the jeopardized cells to a normal status, but that the act of reperfusion itself will lead to the sudden demise of a fraction of the cells because of the cytotoxic effects of reactive species of oxygen derived from one or more of the sources indicated above. The efforts to minimize the amount of tissue that undergoes cell death as a result of myocardial ischemia demand that early reperfusion be established. However, the reintroduction of molecular oxygen and the circulating elements of the blood will be associated with an "explosive" and self-limited destruction of some of the myocardial cells in the area at risk.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Free radicals and myocardial ischemia and reperfusion injury. 329 6

Pathological and clinical studies have suggested that platelets have a role in the pathogenesis of unstable angina and myocardial infarction. However, the relation of platelet activation to episodic ischemia in patients with unstable angina is unknown. We assessed the biosynthesis of thromboxane and prostacyclin as indexes of platelet activation in patients with stable and unstable coronary disease by physicochemical analysis of metabolites in plasma and urine. Prostacyclin biosynthesis was markedly elevated in patients with acute myocardial infarction and correlated with plasma creatine kinase (r = 0.795; P less than 0.001). The largest rise in thromboxane synthesis was observed in patients with unstable angina, in whom 84 percent of the episodes of chest pain were associated with phasic increases in the excretion of thromboxane and prostacyclin metabolites. However, 50 percent of such increases were not associated with chest pain, possibly reflecting silent myocardial ischemia. These data indicate that platelet activation occurs during spontaneous ischemia in patients with unstable angina. The increment in prostacyclin biosynthesis during such episodes may be a compensatory response of vascular endothelium that limits the degree or effects of platelet activation. If so, biochemically selective inhibition of the synthesis or action of thromboxane A2 would be desirable in the treatment of unstable angina. In contrast, thromboxane inhibitors or antagonists would not be expected to be effective in patients with chronic stable angina, in whom there was no increase in the formation of thromboxane A2.
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PMID:Platelet activation in unstable coronary disease. 353 59

Physical activity plays an important role in the prevention of ischaemic heart disease. However, data on the mediating mechanisms are only partly established, and concentrated mainly on plasma lipoproteins. Prostanoids, especially prostacyclin and thromboxane, through their effects on vascular endothelium, platelet function, and interaction with lipoproteins, are postulated to be centrally involved in the pathogenesis of atherosclerosis. The reported acute effects of physical activity on prostanoids and platelet function are contradictory and may be considered both beneficial and unfavourable. On the other hand, although even less is reported on the response to regular exercise, data appear more favourable in relation to atherosclerosis. Currently, data on physical activity and prostanoids, including both acute and chronic effects, are limited and necessitate additional, systematic studies on dose-response relationships.
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PMID:Physical activity and prostanoids. 353 5

Recent evidence indicates that leukocytes (LEU) are large, stiff, viscous cells that naturally adhere to vascular endothelium. Their broad role in the early myocardial microvascular response to acute ischemia was suggested by 1) the role of leukocyte capillary plugging in the no-reflow phenomenon, 2) resistance increases in skeletal muscle with LEU infusions, and 3) salvage of ischemic myocardium by anti-LEU agents. We perfused the coronary circulation under matched, controlled conditions with whole blood or granulocyte-depleted whole blood. During 1 h of ischemia (left anterior descending occlusion) circumflex perfusion pressure was servocontrolled to a constant value. In whole blood-perfused hearts, flow measured by the radiolabeled microsphere method decreased in endocardium from 0.12 +/- 0.05 at 5 min of ischemia to 0.09 +/- 0.04 ml X min-1 X g-1 at 60 min of ischemia and in epicardium from 0.27 +/- 0.17 to 0.21 +/- 0.16 ml X min-1 X g-1, both P less than 0.05. In granulocyte-depleted blood-perfused hearts, flow increased over the same period from 0.18 +/- 0.15 to 0.29 +/- 0.18 ml X min-1 X g-1 in endocardium (P less than 0.05) and did not change significantly in epicardium (0.36 +/- 0.22 to 0.41 +/- 0.24 ml X min-1 X g-1). The LEU-depleted blood perfusate contained less than 33 granulocytes/microliter, whereas control perfusate contained 4,265/microliter. Reperfusion at normal pressures with carbon suspension allowed for histologic evaluation of the no-reflow phenomenon. With whole blood perfusion the no-reflow phenomenon in the endocardium was present with 27% of capillaries occluded, compared with nearly complete reperfusion in LEU-depleted animals (1% of capillaries occluded, P less than 0.05). Furthermore, LEU depletion prevented the increases in tissue water content seen in control hearts and decreased the incidence of ventricular arrhythmias. These studies demonstrate the significant participation of granulocytes in the unfavorable responses of flow, edema formation, and arrhythmias to the 1st h of myocardial ischemia and further document their role in the no-reflow phenomenon.
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PMID:Role of leukocytes in response to acute myocardial ischemia and reflow in dogs. 374 Feb 86

Cardiac ischemia is characterized by rapid deterioration of cardiac function, which has been linked to the fall in intracellular pH, increased levels of inorganic phosphate and reduction in free energy change of ATP-hydrolysis. Biochemical events responsible for irreversible myocardial injury involve various mechanisms which change the properties of the cardiac cell membrane (disorders in lipid metabolism, free radical formation). Recent evidence suggests that in the heart, xanthine oxidase is a major source of free radical formation. During ischemia, adenine-nucleotide breakdown in the cardiomyocyte proceeds only to the stage of inosine. Due to the localisation of nucleoside phosphorylase and xanthine-oxidase in vascular endothelium, further degradation of inosine to hypoxanthine, xanthine and uric acid occurs predominantly in the vascular space. It is therefore conceivable that the primary site of reperfusion injury in the ischemic heart may be the coronary endothelium damaged by free radicals.
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PMID:Mechanisms of ischemic injury in the heart. 390 19

After several hours of ischemia an incomplete return of blood flow has been reported in brain, kidney, skeletal muscle, and heart. The mechanisms responsible for the no-reflow phenomenon have been unclear, and perivascular edema, platelet or red cell plugs, and interstitial hemorrhage have been implicated. In the present study evidence is provided that leukocyte entrapment in capillaries might contribute to no reflow. Leukocytes are large and stiff cells, which adhere to vascular endothelium naturally and are known to alter in their adherence properties under a variety of conditions. Accordingly, 11 open-chest dogs were studied, 1-5 hours after left anterior descending coronary artery occlusion. Reperfusion (9 dogs) at 75 mm Hg arterial pressure was accomplished with Ringer's lactate and carbon suspension as a marker for capillary patency. In non-ischemic tissue, 98% of the capillaries contained carbon, rare leukocytes, and few erythrocytes, whereas tissue from the distribution of the occluded artery was heterogeneous: 60% of the capillaries had no carbon, high hematocrits, and approximately one leukocyte per unbranched capillary; 40% demonstrated reflow and no leukocytes. A significant correlation between capillaries without carbon (no reflow) and the frequency of leukocytes remaining in these capillaries indicated that leukocytes were present in obstructed capillaries. Furthermore, the frequency of leukocytes remaining after the washout with lactate was ten times greater than in normal arrested heart muscle without washout. Our results suggest that progressive leukocyte capillary plugging during myocardial ischemia contributes to preventing full restoration of capillary flow upon reperfusion.
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PMID:Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. 683 25

The aim of the present study was to find out whether plasminogen activator inhibitor type-1 (PAI-1) controls the formation of plasmin in patients with ischaemic heart disease. We examined PAI activity, PAI-1 antigen, tissue type plasminogen activator (t-PA) activity, t-PA antigen, plasmin-alpha2-antiplasmin complex (PAP-complex) and fibrin degradation products D-dimer in 62 patients before (unstimulated) and after infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; stimulated). DDAVP was used in a standardized dose to trigger the release of t-PA from the vascular endothelium. We observed that under basal conditions (unstimulated) median plasma t-PA activity for the whole group of patients was 86.5 mIU/ml (0-900), and after stimulation 2550 mIU/ml (0-6800), P < 0.0001; median plasma concentration of t-PA antigen was 14.7 ng/ml (7.0-115.5) under basal conditions, and after stimulation 34.1 ng/ml (15.8-58.6), P < 0.0001; median plasma PAI activity was 16.9 IU/ml (1.5-144.8) under basal conditions, and after stimulation 3.1 IU/ml (0-118.5), P < 0.0001; median plasma concentration of PAI-1 antigen was 21.5 ng/ml (8.1-132.2) under basal conditions, and after stimulation 14.9 ng/ml (4.8-149.0), P < 0.0001; the median plasma concentration of PAP-complex was 469.5 ng/ml (185.0-1802.0) under basal conditions, and after stimulation 695.5 (243.0-2292.0), P < 0.0001; median plasma concentration of D-dimer was 298.0 ng/ml (103.0-948.0) under basal conditions, and after stimulation 296.5 ng/ml (97.0-917.0), P < 0.0008.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasminogen activator inhibitor type-1 determines plasmin formation in patients with ischaemic heart disease. 748 12

Ischemia of a vascular bed followed by reestablishment of blood flow results in an accelerated and severe form of tissue injury known as "reperfusion injury." We have investigated reperfusion injury in cats subjected to either myocardial ischemia-reperfusion or splanchnic ischemia-reperfusion. In both cases, a critical early event after reperfusion is endothelial dysfunction characterized by reduced release of endothelium-derived relaxing factor now known to be nitric oxide (NO). Endothelial dysfunction leads to adherence of polymorphonuclear (PMN) leukocytes to the dysfunctional endothelium. Infusion of a sydnonimine NO donor (C87-3754), but not a similar compound lacking the NO moiety (C88-3934), just before reperfusion protected in both forms of ischemia-reperfusion. In the first case, C87-3754, but not C88-3934, attenuated myocardial necrosis, and in the second case, the NO donor improved survival and moderated the indices of shock. In both cases, C87-3754 preserved the endothelium of the ischemic-reperfused vasculature and exerted anti-PMN effects (i.e., reduced PMN adherence to the endothelium or attenuated PMN release of superoxide radicals). Thus, an NO donor infused at a rate calculated to replace the lost NO from the vascular endothelium of the ischemic region exerts significant protective effects on reperfusion of that ischemic vascular bed.
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PMID:Protection of ischemia-reperfusion injury by sydnonimine NO donors via inhibition of neutrophil-endothelium interaction. 750 65

Clinical and experimental observations have confirmed that an episodic increase in the vasomotor tone of a major coronary artery may play a pathogenetic role not only in "variant angina" but also in other, more common anginal syndromes. In chronic stable angina, dynamic changes of vascular smooth muscle tone at the site of eccentric atheromatous plaques are responsible for "mixed angina." Abnormal coronary vasomotion contributes to myocardial ischemia in acute coronary syndromes as well. Studies have shown that a "primary" reduction of coronary blood flow, usually associated with plaque fissuring and thrombus formation, causes infarction and unstable angina. Abnormal vasoconstriction associated with the release of vasoactive substances by platelets and other constituents of the thrombus can contribute to coronary flow reduction in patients with unstable angina and myocardial infarction. Better understanding of the complex interactions among atherosclerotic coronary obstructions, the vascular smooth muscle, and the vascular endothelium has resulted in novel therapeutic approaches and has stimulated the search for more efficacious and safer coronary vasodilators. Recently interest has focused on vasodilator agents such as nicorandil that influence coronary arterial tone by acting through potassium channel activation. Nicorandil appears to be effective for treatment of vasospastic angina, as suggested by studies in Japan and Europe. In addition to its "antivasospastic" properties, nicorandil dilates coronary artery stenoses in patients with stable angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Management of vasospastic angina--role of nicorandil. 764 26


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