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)

This study was designed to determine in patients with unstable angina whether specific electrocardiographic abnormalities associated with ischemia, the presence of coronary lesions consistent with thrombosis on angiography or the presence of recurrent ischemia reflects increases in thrombin activity as manifested by increased plasma concentrations of fibrinopeptide A. The concentration of fibrinopeptide A in plasma was increased to 6.7 +/- 3.1 nM for the group as a whole (n = 29). Increases were greater in the 17 patients who exhibited reversible ST segment shifts (10.2 +/- 5.2 nM) than in the 12 patients exhibiting reversible T wave abnormalities alone (1.6 +/- 0.2 nM) (p less than 0.01). Nine of the 17 patients with reversible ST segment shifts who underwent coronary angiography had lesions with morphologic characteristics consistent with atherosclerotic plaque complicated by thrombosis compared with only 2 of 9 patients with T wave changes only (p less than 0.05). Plasma concentrations of fibrinopeptide A were markedly elevated in 7 of the 11 patients in whom complex lesions were noted on angiographic examination. Thus, the occurrence of reversible ST segment shifts identifies a group of patients with unstable angina in whom ongoing thrombosis is likely and who may be particularly likely to benefit from antithrombotic therapy.
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PMID:Relation between ST segment shifts during ischemia and thrombin activity in patients with unstable angina. 189 62

A possible cause of the coronary endothelial injury that occurs with ischemia and reperfusion is the local accumulation of leukocytes during these events. To investigate the role of leukocytes in coronary endothelial injury, we tested the effect of leukocyte removal by filtering on coronary endothelial function in a canine model of regional myocardial ischemia and reperfusion. Blood was supplied to the left anterior descending and circumflex arteries of anesthetized dogs via an extracorporeal circulation. A 60-minute left anterior descending occlusion was followed by 120 minutes of reperfusion either with (n = 6) or without (n = 6) leukocyte filters in the extracorporeal circuit. Regional myocardial blood flow was measured with radiolabeled microspheres. Radiolabeled autologous transferrin (113mIn) and erythrocytes (99mTc) were given intravenously during reperfusion for assessment of microvascular permeability. Left anterior descending and circumflex coronary artery rings were assessed in vitro for endothelium-dependent dilation to acetylcholine, ADP, and thrombin. In unfiltered dogs, ischemia and reperfusion increased the protein leak index of ischemic myocardium 2.3-fold compared with that of nonischemic myocardium (2.3 +/- 0.5 to 5.2 +/- 1.6, p less than 0.05). In filtered dogs, there was no difference in the protein leak index of nonischemic versus ischemic myocardium (1.5 +/- 0.4 versus 1.9 +/- 0.5, p = NS). There was impaired left anterior descending coronary artery relaxation (versus circumflex) in response to endothelium-dependent vasodilators in vitro. However, relaxation was not consistently improved by leukocyte filtering. We conclude that leukocytes are responsible for the endothelial injury secondary to ischemia and reperfusion in the coronary microvasculature but have little or no effect on the endothelial injury in epicardial coronary arteries.
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PMID:Role of leukocytes in coronary vascular endothelial injury due to ischemia and reperfusion. 195 76

The Caerphilly Collaborative Heart Disease Study is based on a large cohort of men (2,398) aged 49-66 years at the time of study. Platelet aggregation induced by collagen, thrombin, and ADP was measured in fasting blood samples and was related to prevalent angina, past myocardial infarction, and electrocardiographic evidence of ischemic heart disease. A number of subjects had taken aspirin, other nonsteroidal anti-inflammatory drugs, or other drugs affecting platelet aggregation 7 days before blood sample collection; after the exclusion of these subjects, data were available for 1,811 men. No relations were demonstrated with angina, but significant relations were shown between past myocardial infarctions and electrocardiographic evidence of ischemia and ADP-induced aggregation (both primary and secondary) and between electrocardiographic evidence of ischemia and thrombin-induced aggregation. The strongest relation indicated more than a twofold increase in the odds of a past myocardial infarction in subjects of the highest fifth of ADP-induced primary platelet aggregation compared with the lowest fifth. No significant relations were detected with collagen-induced aggregation. Accounting for a number of possible confounding factors had a relatively small impact on the relations between platelet aggregation and ischemic heart disease. Other evidence, including the well-established effect of aspirin on reducing the incidence of ischemic heart disease, indicates that the relations we describe are unlikely to be simply an effect of IHD on platelets.
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PMID:Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative Heart Disease Study. 198 96

To examine whether acute myocardial ischemia activates the coagulation system and platelet activation in the coronary circulation, we measured plasma levels of fibrinopeptide A and beta-thromboglobulin in the coronary sinus and the aortic root simultaneously in 15 patients with coronary spastic angina before and after the left coronary spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Fifteen patients with chest pain but normal coronary arteries and no coronary spasm served as controls. The coronary sinus-arterial difference of fibrinopeptide A increased markedly (p less than 0.001) from 0.1 +/- 0.2 to 4.3 +/- 0.7 ng/ml after the anginal attacks in the coronary spastic angina group. However, fibrinopeptide A levels remained unchanged after the attacks in the stable exertional angina group and after intracoronary injection of acetylcholine in the control group. Plasma beta-thromboglobulin levels remained unchanged after the attacks in both patient groups and after acetylcholine in the control group. Our data indicate that coronary spasm induces thrombin generation and may lead to thrombus formation in the coronary artery involved, but pacing-induced ischemia does not activate the coagulation system.
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PMID:Fibrinopeptide A is released into the coronary circulation after coronary spasm. 214 92

The effects of the vasoactive perivascular neuropeptides calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) on proliferation of cultured human umbilical vein endothelial cells (HUVECs) were investigated. CGRP was shown to increase both cell number and DNA synthesis, whereas NKA, NPY, and VIP were ineffective. 125I-labeled CGRP was shown to bind to HUVECs and this binding was displaced by addition of unlabeled CGRP, suggesting the existence of specific CGRP receptors. The effect of CGRP on formation of adenosine 3',5'-cyclic monophosphate (cAMP) and inositol phosphates (InsP), two intracellular messengers known to be involved in regulation of cell proliferation, was investigated. CGRP stimulated cAMP formation but was without effect on the formation of InsP. Proliferation, as well as cAMP formation, was also stimulated by cholera toxin. Basic fibroblast growth factor stimulated growth without affecting cAMP or InsP formation, whereas thrombin, which increased InsP formation, did not stimulate proliferation. We thus suggest that CGRP may act as a local factor stimulating proliferation of endothelial cells; that the mechanism of action is associated with cAMP formation; and that this effect of CGRP may be important for formation of new vessels during physiological and pathophysiological events such as ischemia, inflammation, and wound healing.
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PMID:Calcitonin gene-related peptide stimulates proliferation of human endothelial cells. 215 44

Rupture of an atherosclerotic plaque associated with partial or complete thrombotic vessel occlusion is fundamental to the development of ischemic coronary syndromes. Plaques that produce only mild-to-moderate angiographic luminal stenosis are frequently those that undergo abrupt disruption, leading to unstable angina or acute myocardial infarction. Plaques with increased lipid content appear more prone to rupture, particularly when the lipid pool is localized eccentrically within the intima. Macrophages appear to play an important role in atherogenesis, perhaps by participating in the uptake and metabolism of lipoproteins, secretion of growth factors, and production of enzymes and toxic metabolites that may facilitate plaque rupture. In addition, the particular composition or configuration of a plaque and the hemodynamic forces to which it is exposed may determine its susceptibility to disruption. Exposure of collagen, lipids, and smooth muscle cells after plaque rupture leads to the activation of platelets and the coagulation cascade system. The resulting thrombus may lead to marked reduction in myocardial perfusion and the development of an unstable coronary syndrome, or it may become organized and incorporated into the diseased vessel, thus contributing to the progression of atherosclerosis. In unstable angina, plaque disruption leads to thrombosis, which is usually labile and results in only a transient reduction in myocardial perfusion. Release of vasoactive substances, arterial spasm, or increases in myocardial oxygen demand may contribute to ischemia. In acute myocardial infarction, plaque disruption results in a more persistent thrombotic vessel occlusion; the extent of necrosis depends on the size of the artery, the duration of occlusion, the presence of collateral flow, and the integrity of the fibrinolytic system. Thrombi that undergo lysis expose a highly thrombogenic surface to the circulating blood, which has the capacity of activating platelets and the coagulation cascade system and may lead to thrombotic reocclusion. Measurements aimed at reversing the process of atherosclerosis via cholesterol reduction and enhanced high density lipoprotein activity are encouraging. Active research is being focused on the development of new antithrombotic tools, such as inhibitors of thrombin, thromboxane, and serotonin receptor antagonists, and monoclonal antibodies aimed at blocking platelet membrane receptors or adhesive proteins. These compounds may prove useful when immediate and potent inhibition of the hemostatic system is desired. Intensive research is still needed in the areas of pathogenesis and therapeutic intervention in atherosclerosis.
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PMID:Atherosclerotic plaque rupture and thrombosis. Evolving concepts. 220 64

Experiments were designed and performed to determine whether endothelial function remained chronically impaired after coronary artery reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia (60 minutes) followed by reperfusion (12 weeks). Rings (3-4 mm wide) of the reperfused artery and of normal left circumflex (control) coronary artery segments were suspended in organ chambers containing physiological saline solution (37 degrees C, gassed with 95% O2-5% CO2) for isometric force measurement. Endothelium-independent contractions to KCl or prostaglandin F2 alpha and endothelium-independent relaxations to nitric oxide or isoproterenol were comparable in control and chronically reperfused arteries. However, chronically reperfused coronary arteries exhibited impaired endothelium-dependent relaxations to aggregating platelets. In addition, the reperfused coronary arteries exhibited impaired endothelium-dependent relaxations to the platelet-derived compounds adenosine diphosphate, serotonin, and thrombin. However, the endothelium-dependent relaxations to acetylcholine were comparable between control and reperfused arteries. Thus, after 12 weeks of reperfusion, previously occluded coronary arteries exhibited a selective impairment of endothelium-dependent relaxation evoked by aggregating platelets. In vivo, this phenomenon could favor platelet adhesion, aggregation, and platelet-induced contraction of coronary smooth muscle and thus facilitate ischemic events such as vasospasm and coronary thrombosis.
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PMID:Long-term impairment of endothelium-dependent relaxations to aggregating platelets after reperfusion injury in canine coronary arteries. 234 84

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

Injury to the endothelial lining of arteries is an important mechanism in both the early and late stages of the development of atherosclerosis. Platelets can contribute to the early lesions by releasing factors that cause smooth muscle cell migration and proliferation. In the later stages, the formation of large platelet-fibrin thrombi that become organized into the vessel wall contributes to the development of focal atherosclerotic narrowing of arteries. Injury to the vessel wall can also be a factor in causing spasm of coronary arteries, particularly at sites of stenosis. The spasm may cause ischemia, anginal pain, and, in some individuals, ventricular fibrillation and death. In other individuals, the spasm may not cause death but may persist long enough for an occlusive thrombus to form and cause myocardial infarction. The events leading to thrombosis involve not only the release of arachidonic acid and the formation of TXA2, but other pathways that are independent of the arachidonate pathway. In some circumstances thrombin (which causes platelet aggregation and release that are largely independent of the arachidonate pathway and TXA2 formation) is the primary stimulus causing the initiation and growth of the thrombus. The role of products of the arachidonate pathway in causing spasm is not understood. PGI2 produced by the vessel wall could be important in preventing or minimizing coronary artery spasm. The best way to prevent the development of atherosclerosis and its clinical complications is to prevent or minimize injury of the endothelium.
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PMID:Platelets, endothelium, and vessel injury. 315 7

Clinical pathology is a valuable adjunct to physical examination of cases of colic. The present review considers evaluation of cases of colic for three main purposes: (1) making a prognosis, (2) deciding whether to operate, and (3) making a diagnosis. Blood tests noted to be useful for prognostication were hematocrit, lactate and urea nitrogen concentrations, pH, anion gap, fibrin/fibrinogen degradation products, antithrombin III activity, prothrombin time, and thrombin time. Horses with a poor prognosis often have relative polycythemia, marked lactic acidosis, high anion gap, azotemia, and coagulation abnormalities evidenced by increased fibrin/fibrinogen degradation products, decreased antithrombin III activity, and prolonged prothrombin and thrombin times. The decision to operate is usually a clinical one, supported by relative polycythemia, hyperglycemia, and, possibly, abnormal peritoneal fluid analysis. Diagnosis of the primary problem (causing the colicky signs) is also often based largely on physical examination. However, peritoneal fluid analysis provides worthwhile data, especially in cases of peritonitis or intestinal ischemia and infarction.
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PMID:Use of clinical pathology in evaluation of horses with colic. 332 25


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