Protection of the myocardium during myocardial infarction: pharmacologic protection during thrombolytic therapy

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.)