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A heart attack is a manifestation of a great many contributing factors, often including the development, over many years, of atherosclerotic plaques within the coronary arteries. The event precipitating a heart attack may be the rupture or ulceration of an atherosclerotic plaque. Platelets (blood cells involved in clotting) adhere to the ruptured plaque, aggregate, and initiate the development of a thrombus (blood clot). This thrombus is likely to become a thromboembolus, that is, likely to occlude (block) a smaller artery and impede blood flow to the heart muscle. A great step forward in the treatment of heart attack is thrombolysis, the use of enzymes, such as streptokinase or plasminogen activator, to dissolve such blood clots. If the blood clot dissolves and if blood flow to the oxygen-starved heart muscle can be restored before it is permanently damaged, the chances for recovery are excellent. However, improvements in this important therapeutic method are still possible, both in how quickly the thrombus is dissolved and in reducing the likelihood that a new clot will form after the first is dissolved. While heparin treatment is currently recommended as an anticoagulant adjunct therapy (with or immediately after thrombolysis), additional agents that act directly on platelets may prove to be of value. Aspirin has long been known to inhibit platelet function and blood clotting, but it is not yet known to what degree aspirin might be valuable as a part of thrombolytic therapy. Newly developed agents may also provide useful antiplatelet action, although these have, in general, been tested only in experimental animals. These include a monoclonal antibody that blocks the glycoprotein IIb/IIIa receptor on the platelets, and a chemically complex synthetic substance that binds to and inhibits the enzyme thrombin. It remains to be determined, however, if such substances will prove to be of value in clinical trials involving human patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Unstable angina, chest pain that increases in frequency with progressively less activity, often occurs when the patient is at rest, and acute myocardial infarction (MI or heart attack) are manifestations of acute coronary artery disease (CAD). Unstable angina is sometimes a result of damage to the cells lining the arterial walls or fissures in an atherosclerotic plaque. The authors speculate that unstable angina, non-Q-wave MIs, and Q-wave MIs represent progressively more serious points on a continuum, rather than distinct conditions. The Q-wave represents a phase of the heart beat as measured on an electrocardiogram. It is suggested that the potential causes of this progression include injury to the lining of the arterial walls from cracks in plaques, hypertension or stress, infection, smoking, coronary arteriography (in which a catheter is used to inject dye into the coronary arteries for X-ray contrast) or angioplasty ( in which a catheter is inserted in an artery to reduce narrowing). The conversion from a chronic to an acute state may be caused by accumulation of thromboxane A2, and consequent tendency to clotting and constriction of the artery, but a causal relationship could not be established. Working with dogs, the authors found that a thromboxane synthesis inhibitor protected against cyclical changes in heart blood flow. They also found that serotonin concentration increases 18-fold at the narrowed or injured site when these cyclic deceases occur. If clotting and the resulting release of thromboxane and serotonin cause or sustain some CAD syndromes, therapy to inhibit this release should benefit the patient. Aspirin inhibits thromboxane synthesis and clotting, and has been shown to reduce risk of MI and death in patients with unstable angina. The authors' hypothesis is in agreement with this finding. In order to protect patients from progressing from stable angina to MI, it may be necessary to employ thromboxane and serotonin receptor antagonists, or a combination of thromboxane synthesis inhibitor and a receptor antagonist with a serotonin receptor antagonist. (Consumer Summary produced by Reliance Medical Information, Inc.)

The most effective way to protect injured myocardium during the early phases of evolving myocardial infarction is with reperfusion. However, reperfusion may induce further myocardial injury. Alterations in the major determinants of myocardial oxygen demand, including increases in heart rate, contractile state and myocardial wall tension may also increase infarct size. An understanding of the basic mechanisms involved in the evolution of myocardial injury during myocardial infarction is important to the development of protective strategies that may reduce infarct size or attenuate repertusion-induced myocardial injury, or both. Selective calcium antagonists, [Beta] blockers, and phospholipase antagonists or inhibitors may reduce infarct size in association with early reperfusion. Reperfusion injury may be attenuated by free radical scavengers and calcium antagonists. Reinfarction, after the initial event, may ultimately be reduced in frequency by pharmacologic strategies that interfere with platelet adhesion, aggregation, and mediator release from activated platelets and white cells that promote further platelet aggregation or induce coronary artery vasoconstriction. included among protective strategies are thromboxane receptor antagonists and synthesis inhibitors, serotonin receptor antagonists, possibly leukotriene synthesis inhibitors or receptor antagonists, and aspirin. Future clinical trials should test the combined efficacy of reperfusion and selected pharmacologic strategies that alter calcium accumulation in the injured myocardium, diminish the injurious effects of [Beta]- and [alpha]adrenergic mechanisms and oxygen-derived free radicals on injured myocytes, and prevent reocclusion mediated by platelets and platelet mediators. (Am J Cardiol 1990;65-35 I-41 I), Myocardial infarction (MI) is a heart attack caused by the deterioration of heart tissue due to cessation of blood supply to the heart muscle, and may result from clot formation, narrowing, or rupture of the blood vessel supplying the heart. Initial studies showed that tissue damage in MI may be reduced by reperfusing, restoring blood flow, within three hours from onset of the ischemia. However, it was later shown that reperfusion and the restoration of oxygen supply to injured (infarcted) tissue can cause further tissue damage due to highly reactive oxygen free radicals produced during oxygen metabolism. Factors affecting the oxygen demand of the heart such as heart rate, contractility, and tension or stress may also influence the size of the infarct. The mechanisms leading to tissue injury in MI must be determined in developing approaches for reducing infarct size and preventing further tissue damage due to reperfusion. Tissue damage from reperfusion may be reduced by calcium antagonists, beta blockers, phospholipase inhibitors, and free radical scavengers. The recurrence of MI can be prevented by the use aspirin, which prevents blood clotting, and agents that prevent the production or the actions of the following: thromboxane, which activates blood clotting; serotonin, which constricts blood vessels; and leukotriene, which activates inflammation. The combined effectiveness of reperfusion and agents that prevent the progression of tissue damage in MI and recurrence of MI require further investigation. (Consumer Summary produced by Reliance Medical Information, Inc.)

The application of noninvasive nuclear medicine imaging techniques to the study of patients with suspected or known cardiovascular diseases offers important diagnostic, pathophysiologic and prognostic information that may directly affect [...]