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 reperfusion-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.