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)

From many observations made at autopsy it is apparent that thrombosis in a coronary artery is usually, if not always, associated with rupture of an atheromatous plaque. The sequelae of such rupture include hemorrhage into the plaque with further narrowing of the lumen, formation of an occlusive thrombus or of a non-occlusive thrombus. A developing thrombus in an artery undergoes fragmentation with showering of the distal microcirculation by aggregates of platelets possibly with some admixture of fibrin. In many cases of sudden cardiac death associated with severe atherosclerotic stenosis of the coronary vessels, an occlusive thrombus is not found and the myocardium shows no morphological lesion or else focal patchy early damage in the subendocardial region. One possible mechanism that might explain these findings is microembolism from mural nonobstructing coronary thrombus. Such a mechanism is well established in transient ischemia of the brain and retina related to ulcerated atheroma of the internal carotid artery. Experimental observations indicate that platelet aggregates in the myocardial circulation cause arrhythmias, sudden death, vasculitis, and myocardial ischemic damage. Induction of an occlusive coronary artery thrombus is associated with development of an infarct involving the full thickness of the myocardium. A nonocclusive thrombus is associated with either no myocardial damage or focal subendocardial ischemic injury. It is possible that further aggregation of platelets may facilitate the extension of infarction subsequent to an occlusive event, although there is little evidence on this point. A number of clinical studies show increased platelet reactivity to agents causing aggregation, such as norepinephrine or collagen, in subjects experiencing thromboembolic episodes. It seems unlikely, however, that in vitro tests of platelet function can identify or predict clinical arterial thrombotic disease, although studies of platelet survival and turnover may be more helpful. There is also evidence that platelet survival may be prolonged by drugs having a therapeutic benefit in coronary artery disease and arterial thromboembolism. There is a need for better designed and coordinated clinical trials and for better experimental approaches to explore the relationships among coronary thrombosis, embolsim of the myocardial microcirculation, myocardial ischemia, and sudden death.
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PMID:Platelet aggregation secondary to coronary obstruction. 76 18

Coronary artery thrombosis plays a major role in the acute ischemic coronary artery syndromes in which fibrinopeptide A (FPA) has proved to be a sensitive marker. The purpose of this study was to determine FPA concentrations in patients with acute coronary artery syndromes and to determine if these could serve as a short-term prognostic indicator. Single plasma FPA levels were measured in 26 patients with acute ischemic coronary artery syndromes within 24 hours of the onset of chest pain as well as in 12 patients with chronic stable angina and in 9 control subjects. Higher FPA levels were observed in patients with unstable angina whom later developed recurrence of chest pain compared to those without (8.1 +/- 3.4 vs. 3.4 +/- 2.2; p = 0.01). Neither the localization of ischemia, presence of complications, need for revascularization nor short-term prognosis (6 months) correlated with the plasma FPA concentration. Therefore, except for recurrence of chest pain in patients with unstable angina, the finding of an elevated FPA level upon admission did not provide additional information regarding clinical course and prognosis than that obtained in a detailed clinical history, physical examination and initial electrocardiogram in patients with acute ischemic artery syndromes.
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PMID:Usefulness of single fibrinopeptide A determination in patients with acute ischemic coronary artery syndromes. 129 2

We examined the effect of coronary thrombolysis by recombinant tissue-plasminogen activator (rtPA) on infarct size using a thrombin-induced thrombosis model of open-chest anesthetized dog. Occlusive thrombus was induced by injection of thrombin (100 U) in the left anterior descending coronary artery (LAD). The intravenous infusion of rtPA (10 micrograms/kg/min) was started at 30 min (30 min-ischemia group) or at 60 min (60 min-ischemia group) after the formation of thrombus, and was continued for 30 min. Spontaneous thrombolysis was not observed in the 360 min-ischemia (vehicle-treated) group. Intravenous infusion of rtPA elicited thrombolysis within 30 min in all the dogs except in one in the 60 min-ischemia group. The infarct size was significantly reduced by rtPA-induced thrombolysis. The shorter the duration of the ischemia, the longer the effect of the drug, and the infarct size after thrombolysis was smaller in the 30 min-ischemia group than in the 60 min-ischemia group. Ischemia-induced changes in ST-segment of electrocardiogram (ECG) were significantly ameliorated after thrombolysis in both 60 min- and 30 min-ischemia group. These results suggest that early reperfusion of coronary thrombosis by rtPA is beneficial to the ischemic myocardium.
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PMID:Early thrombolysis by recombinant tissue-plasminogen activator is beneficial to the ischemic myocardium. 160 39

Cocaine use has increased in recent years, in part as a result of the increased availability of "crack," the inexpensive freebase form. Although it is used medicinally and initially was considered a relatively safe street drug, cocaine clearly has addictive potential as well as adverse health consequences even in low doses. Some of its most serious adverse effects involve the cardiovascular system. Understanding the cellular mechanisms of the action of cocaine on the heart allows insight into the pathophysiology of its adverse effects. Blockade of sodium channels accounts for cocaine's anesthetic effects and acts directly on myocytes to impair action potential generation and conduction, predisposing to dysrhythmias. Blockade of neurotransmitter reuptake has many deleterious effects, including dysrhythmogenesis via increased intracellular calcium, myocardial ischemia via vasospasm and increased myocardial oxygen demand, and contraction band necrosis also via increased intracellular calcium. In addition, alterations in platelet-endothelial cell function predispose to coronary artery thrombosis and ischemia. Alterations in immune function of natural killer cells may, among other effects, predispose to the development of myocarditis, the etiology of which is probably multifactoral. Finally, a direct toxic effect of cocaine on myocytes may, in some cases, produce heart muscle dysfunction. These multiple mechanisms of action combined with the deleterious effects of often-present adulterants give rise to an unpredictable, variable, and potentially life-threatening cardiovascular response to cocaine administration.
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PMID:Cocaine-induced heart disease: mechanisms and pathology. 167 Dec 28

Activated neutrophils and possibly xanthine oxidase-derived free radicals are believed to be mediators of ischemia and reperfusion-induced myocardial damage. We studied the cardioprotective effect of the neutrophil stabilizer and xanthine oxidase inhibitor azapropazone in dogs subjected to thrombotic occlusion of the left anterior descending coronary artery (LAD), induced by intracoronary introduction of a copper coil, followed 60 min later by thrombolytic treatment with intracoronary streptokinase and 4-day reperfusion; we then determined infarct size by triphenyltetrazolium stain. Azapropazone [100 mg/kg intravenously (i.v.) followed by a 24-h i.v. infusion of 10 mg/kg/h, n = 8] or vehicle (n = 10) treatments were started immediately before the streptokinase infusion. Steady-state plasma levels of azapropazone ranged from 97 to 163 micrograms/ml during the infusion. Myocardial blood flow and underperfused area at risk were determined using radiolabeled microspheres. Results were as follows (mean +/- SEM): area at risk (percentage of left ventricle) azapropazone 22.7 +/- 3.16 and vehicle 21.8 +/- 4.13; infarct size (percentage of area at risk), azapropazone 45.1 +/- 11.8 and vehicle 75.7 +/- 10.6, p less than 0.03; collateral blood flow (ml/min/g), azapropazone 0.27 +/- 0.02 and vehicle 0.23 +/- 0.02; total ischemic period (min), azapropazone 106 +/- 5.9 and vehicle 91.5 +/- 4.9. Azapropazone had no effects on heart rate (HR), blood pressure (BP), or rate/pressure product (RPP). These dta show that azapropazone limits infarct size in a canine model of coronary thrombosis and long-term reperfusion and that this cardioprotection is independent of cardiovascular parameters.
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PMID:Persistent cardioprotection by azapropazone in a canine model of coronary artery thrombosis and thrombolysis. 171 99

With regard to cardiac findings in cocaine abuse, at autopsy the vast majority of patients dying with cocaine toxicity have either no pathologic change in the heart or only minimal changes that could not account for the patient's death. The second most frequent finding is underlying, mild-to-moderate coronary atherosclerosis, with or without coronary thrombosis. There may be acute or healed myocardial infarction or a sudden cardiac death without myocardial changes of ischemia. A high incidence of contraction band necrosis has been reported in the absence of coronary artery disease and may cause a sudden arrhythmic death. Myocarditis also has been described in a few cases as either lymphocytic or lymphocytic and eosinophilic infiltrate in the presence of myocyte necrosis. Usually, the foci are sparse and not always associated with contraction band necrosis. The underlying mechanisms are thought to be either direct effects of norepinephrine on myocytes or through vasospasm of resistance vessels and secondary myocardial ischemia. Cocaine rarely has been associated with aortic dissection, which is probably a result of cocaine's hypertensive effects.
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PMID:Cocaine-associated cardiovascular disease: clinical and pathological aspects. 174 14

The very first presentation of ischemic heart disease--acute infarction, sudden death, or unstable angina--most often occurs abruptly. The first approximation that it occurs as a random event only when a certain "threshold severity" of coronary atherosclerosis has gradually developed, although widely accepted, should perhaps be reconsidered and expanded on the basis of the following considerations. Acute coronary occlusion leading to myocardial infarction often occurs at the site of mild or noncritical coronary stenoses. Conversely, in patients with chronic angina severe coronary stenoses can remain unchanged for years with no detectable progression. When a coronary artery occludes, the size of infarction can vary greatly, and when ischemia and infarction occur, malignant arrhythmias occur in some patients but not in others. Thus, in a second approximation, ischemic heart disease should be considered as the result of the variable combination of three major components: a) A very variable chronic atherosclerotic background, which can result from a variety of pathologic processes; b) A number of acute ischemic stimuli, which can unpredictably impair myocardial blood flow as a result of coronary thrombosis and/or vasoconstriction; c) A variable response of the heart to a sudden reduction of coronary blood flow in terms of collateral perfusion and malignant arrhythmias. Therefore, at one extreme end of the spectrum in any individual, ischemic syndromes may present predominantly as a result of an extremely large chronic background component. At the other extreme, powerful acute ischemic stimuli can unexpectedly impair blood supply by coronary thrombosis, constriction, or their combination, in the presence of a mild chronic atherosclerotic background.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of myocardial ischemia. 209 77

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

Episodic platelet activation has been shown to occur in unstable angina, and aspirin should have an important therapeutic role in the management of these patients. The response to aspirin alone or to aspirin in combination with vasodilators such as heparin and beta-blockers has been assessed in 41 patients with unstable angina. Therapy was added sequentially in the event of recurrence of transient myocardial ischemia. Patients were randomly assigned to two groups. Group 1 (21 patients) received an intravenous infusion of isosorbide dinitrate and oral diltiazem, and group 2 (20 patients) received intravenous aspirin (60 mg the first day and 20 mg on successive days). This dose of aspirin reduced serum thromboxane B2 from 160 +/- 88 ng/ml (mean +/- SD) to undetectable values (less than 6 ng/ml, p less than 0.01). If episodes of ischemic ST segment shift continued, the therapy of group 1 was added to that of group 2 or vice versa; if further ST segment changes were documented, intravenous heparin and oral beta-blockers were added; if episodes of myocardial ischemia persisted, urgent coronary arteriography and myocardial revascularization were performed. Nine patients in group 1 and six in group 2 (p = 0.8) had no further episodes of myocardial ischemia on their initial therapy; 12 additional patients had no further episodes when taking combined therapy of aspirin and vasodilators. Thus, the administration of aspirin alone was not superior to coronary dilators; 30% of all patients continued to have episodes of myocardial ischemia or had a myocardial infarction develop when heparin and beta-blockers were added. Myocardial infarction occurred in one patient on vasodilator therapy alone, in two on combined therapy, and in two on full therapy. These results suggest that in some patients, the stimulus to coronary thrombosis and vasoconstriction occasionally becomes so strong that it cannot be inhibited by certain antagonist drugs. The unstable tendency to continuation of ischemia or evolution to myocardial infarction is not related to the severity of the persisting stenosis. Those patients not promptly responding to combined therapy immediately from admission should have early coronary angiography and aggressive treatment.
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PMID:Comparison of low-dose aspirin and coronary vasodilators in acute unstable angina. 240 67

Thrombolytic therapy has gained widespread acceptance as a means of treating coronary artery thrombosis in patients with acute myocardial infarction. Although experimental data have demonstrated that timely reperfusion limits the extent of infarction caused by regional ischemia, there is growing evidence that reperfusion is associated with an inflammatory response to ischemia that exacerbates the tissue injury. Ischemic myocardium releases archidonate and complement-derived chemotactic factors, e.g., leukotriene B4 and C5a, which attract and activate neutrophils. Reperfusion of ischemic myocardium accelerates the influx of neutrophils, which release reactive oxygen products, such as superoxide anion and hydrogen peroxide, resulting in the formation of a hydroxyl radical and hypochlorous acid. The latter two species may damage viable endothelial cells and myocytes via the peroxidation of lipids and oxidation of protein sulfhydryl groups, leading to perturbations of membrane permeability and enzyme function. Neutrophil depletion by antiserum and inhibition of neutrophil function by drugs, e.g., ibuprofen, prostaglandins (prostacyclin and PGE1), or a monoclonal antibody, to the adherence-promoting glycoprotein Mo-1 receptor, have been shown to limit the extent of canine myocardial injury due to coronary artery occlusion/reperfusion. Recent studies have challenged the hypothesis that xanthine-oxidase-derived oxygen radicals are a cause of reperfusion injury. Treatment with allopurinol or oxypurinol may exert beneficial effects on ischemic myocardium that are unrelated to the inhibition of xanthine oxidase. Furthermore, the human heart may lack xanthine oxidase activity. Further basic research is needed, therefore, to clarify the importance of xanthine oxidase in the pathophysiology of reperfusion injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial ischemia and reperfusion: the role of oxygen radicals in tissue injury. 248 90


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