Cardiodepressive mediators are released after ischemia from an isolated heart: role of coronary endothelial cells

Medizinische Klinik, Institut fur Pathologie Rudolf Virchow, Universitatsklinikum Charite, Humboldt-Universitat zu Berlin, Germany.

OBJECTIVES: This study was designed to ascertain whether cardiodepressive mediators released after ischemia originate from coronary endothelial cells. BACKGROUND: Endothelial cells modulate myocardial contractility under physiologic conditions. Few data are available describing the role of coronary endothelial cells on myocardial function after ischemia. 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 coronary endothelium of heart I was functionally removed by Triton X-100 or 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 sequential perfusion. In contrast, after 10 min of ischemia in heart I, a marked reversible decrease in left ventricular pressure, left ventricular dP/dtmax and left ventricular dP/dtmin (-55%, -66% and -70%, respectively) was observed in heart II. Heart rate and coronary perfusion pressure did not change significantly. Selective endothelial damage of heart I before ischemia did not modify the negative inotropic effect observed in heart II. CONCLUSIONS: Cardiodepressive mediators are released after ischemia during reperfusion from an isolated heart and induce a reversible negative inotropic effect in a sequentially perfused heart. It is unlikely that these agents are derived from the coronary endothelium.

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