Experimental lesions of the coronary arteries and heart after intrapericardial injection of proteolytic enzymes.

Myocardial infarction in experimental animals lhas been successfully produced by ligating coronary artery branclhes(l), by injecting obstructing materials into the coronary vessels themselves(2), by external compression(3), and by intravascular electrocoagulation(4). Also, in rats Tlhomas an(l Hartroft were able by dietary means to procluce coronary thrombosis associated witlh myocardial necrosis(5). In this laboratory progressive closure of major coronary arteries in the (log was accomplislhedl many years ago by the intravenous injection of allylamine(6). Altlhouiglh allylamine severely damaged the coronary arteries of the treate(d animals, thrombi andI myocardial infarction were decidedly rare. This observation raised major questioins as to the types and degrees of injury in the walls of coronary arteries that ar-e critical for their thrombotic occlusion. Also questioITs were raise(d as to the pathogenesis of myocardial infarction. That coronary thrombosis andl myocardial infarction do occur in man in association witlh atlherosclerosis is common knowledge, but relatively little is known concerning the precise local condlitions in wlhiclh these important lesions arise. Constantinides(7), andl Friedman and Van Den Bovenkamp(8) lhave found by examiniation of serially sectioned tlhrombosed coronary arteries, tllat in the vast majority a fissure or crack is present in the vessel wall connecting the underlying atlheroma andl the overlying thrombus. Presumably a tlhrombuls may form at or near an actively autolyzing tissue site (atlheroma) in the artery wall. The present experiments had as their objective the creation of an enzymatic counterpart of an autolyzing arterial atlheroma and(I the testing of suclh a lesion in promoting coronary artery tlhrombosis. The plan of the experiments was to introduce potent proteolytic enzymes directly into the pericardial sacs of anestlhetized dogs at thioracotomy andl to stutly at varying intervals tlhereafter the action of tllese sub-