. 2015 Nov; 170(5):971-80.
doi: 10.1016/j.ahj.2015.08.005.

Reperfusion therapy for acute myocardial infarction: Concepts and controversies from inception to acceptance

Klaus Peter Rentrop 1 Frederick Feit 2 
  • PMID: 26542507
  •     21 citations


More than 20 years of misconceptions derailed acceptance of reperfusion therapy for acute myocardial infarction (AMI). Cardiologists abandoned reperfusion for AMI using fibrinolytic therapy, explored in 1958, because they no longer attributed myocardial infarction to coronary thrombosis. Emergent aortocoronary bypass surgery, pioneered in 1968, remained controversial because of the misconception that hemorrhage into reperfused myocardium would result in infarct extension. Attempts to limit infarct size by pharmacotherapy without reperfusion dominated research in the 1970s. Myocardial necrosis was assumed to progress slowly, in a lateral direction. At least 18 hours was believed to be available for myocardial salvage. Afterload reduction and improvement of the microcirculation, but not reperfusion, were thought to provide the benefit of streptokinase therapy. Finally, coronary vasospasm was hypothesized to be the central mechanism in the pathogenesis of AMI. These misconceptions unraveled in the late 1970s. Myocardial necrosis was shown to progress in a transmural direction, as a "wave front," beginning with the subendocardium. Reperfusion within 6 hours salvaged a subepicardial ischemic zone in experimental animals. Acute angiography provided in vivo evidence of the high incidence of total coronary occlusion in the first hours of AMI. In 1978, early reperfusion by transluminal recanalization was shown to be feasible. The pathogenetic role of coronary thrombosis was definitively established in 1979 by demonstrating that intracoronary streptokinase rapidly restored flow in occluded infarct-related arteries, in contrast to intracoronary nitroglycerine which rarely did. The modern reperfusion era had dawned.

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