CARDIODEPRESSIVE MEDIATORS ARE RELEASED AFTER ISCHEMIA FROM AN ISOLATED HEART - ROLE OF CORONARY ENDOTHELIAL-CELLS

Objectives. This study was designed to ascertain whether car diodepres sive mediators released after ischemia originate from coronary endothe lial cells. Background. Endothelial cells modulate myocardial contract ility under physiologic conditions, Few data are available describing the role of coronary endothelial cells on myocardial function after is chemia. Methods. Using a model of sequential perfusion of two isolated rat hearts, the effect of the reoxygenated coronary effluent of heart I was investigated on myocardial contractility of heart II. After 40 min of separate perfusion at constant flow (10 ml/min), the two hearts were perfused sequentially with (group I) or without (control group) preceding ischemia (10 min) of heart I. In groups II and III, the coro nary endothelium of heart I was functionally removed by Triton X-100 o r hyperkalemic infusion before global ischemia. Endothelial damage was confirmed by functional tests and electron microscopy. Results. Under control conditions no changes were observed in heart II during sequen tial perfusion. In contrast, after 10 min of ischemia in heart I, a ma rked reversible decrease in left ventricular pressure, left ventricula r dP/dt(max) and left ventricular dP/dt(max) (-55%, -66% and -70%, res pectively) was observed in heart II. Heart rate and coronary perfusion pressure did not change significantly. Selective endothelial damage o f heart I before ischemia did not modify the negative inotropic effect observed in heart II. Conclusions. Cardiodepressive mediators are rel eased after ischemia during reperfusion from an isolated heart and ind uce a reversible negative inotropic effect in a sequentially perfused heart. It is unlikely that these agents are derived from the coronary endothelium. (C) 1997 by the American College of Cardiology.