Development and Pathophysiological Basis of Thrombolytic Therapy in Acute Myocardial Infarction: Part III, 1981–1985 Registries of Intracoronary Thrombolytic Therapy and Experimental Reperfusion Studies

The angiographic results of intracoronary thrombolysis were correlated with various outcome parameters in three registries. The West German Registry (n = 232) showed that mortality and improvement of left ventricular function were related to recanalization and prevention of reocclusion. This registry became the core database for the Food and Drug Administration (FDA) approval of thrombolytic agents for myocardial infarction in 1982. The European Registry (n = 414) analyzed changes in left ventricular ejection fraction further. A continuous model suggested that the functional benefit of reperfusion decreases rapidly and in a nonlinear fashion with delays in treatment during the first 3 hours. Reperfusion after > 6 hours was still associated with a significant benefit, which appeared to be related to collateral flow to the infarct zone. Myocardial salvage in experimental reperfusion studies and the reperfusion injury controversy are reviewed. In experimental studies performed by our group, it was found that thrombolytic agents did not exacerbate myocardial hemorrhage or increase infarct size. The Goettingen Registry (n = 152) demonstrated that reperfusion resulted in a steeper slope of the regression line between infarct size determined by ventriculography and cumulative serial creatine kinase release. Furthermore, reperfusion was associated with transient loss of R waves and transient development of Q waves. The implications of these findings regarding the reperfusion injury controversy and assessment of infarct size are discussed. Other analyses of the Goettingen data found that flow patterns to the infarct zone at preintervention angiography correlated with the duration of angina pectoris, incidence of antianginal therapy, and baseline ejection fraction. Assessment of the reliability of the admission ECG showed that half of the patients with infarction due to occlusion of the circumflex artery lacked diagnostic changes. The Goettingen Registery followed the first group of 70 patients ever treated with intracoronary thrombolytic therapy for 3 years. Mortality was low by the standards of the time. Reperfusion was associated with sustained improvement of left ventricular function and often dramatic clinical stabilization not seen before.