Coronary thrombolysis with tissue-type plasminogen activator (t-PA): emerging strategies

Fundamental observations and the conceptual framework underlying coronary thrombolysis have a history dating back to 1789. Recent enthusiasm for it is predicated on the recently established safety of cardiac catheterization in critically ill patients, the high incidence of coronary thrombosis underlying acute transmural myocardial infarction and demonstrable benefit conferred to the heart and the patient when thrombolysis is initiated early after the onset of ischemia. Clot-selective activators of the fibrinolytic system offer promise for safe induction of coronary thrombolysis without marked predisposition to bleeding. One such activator, tissue-type plasminogen activator (t-PA), has been synthesized by recombinant deoxyribonucleic acid (DNA) technology, amenable to large scale production of pharmaceutical agents and hence widespread availability. Initial clinical trials conducted with t-PA have demonstrated opening rates of completely occluded, infarct-related coronary arteries of approximately 75% without marked depletion of fibrinogen. The focus of research in progress includes: noninvasive delineation of recanalization and estimation of the extent of myocardium salvaged by initial recanalization, development of alternative routes of administration of thrombolytic agents potentially exploitable by paramedical personnel and, perhaps, high risk patients themselves, and definitive elucidation of the extent to which benefits conferred by thrombolysis can be enhanced with adjunctive pharmacologic interventions as well as early angioplasty or surgery.