A STUDY ON DILAZEP .1. MECHANISM OF ANTIISCHEMIC ACTION OF DILAZEP ISNOT CORONARY VASODILATION BUT DECREASED CARDIAC MECHANICAL FUNCTION IN THE ISOLATED, WORKING RAT-HEART

In the isolated, perfused working rat heart, ischemia (15 min) decreas ed the mechanical function and the tissue levels of adenosine triphosp hate and creatine phosphate and increased the levels of lactate and fr ee fatty acids. Reperfusion (20 min) did not restore the mechanical fu nction, but restored incompletely the levels of metabolites, with the exception of free fatty acids, which increased further during reperfus ion. Dilazep was given 5 min before starting ischemia until the end of ischemia. Dilazep at 5 or 10 mu M decreased the cardiac mechanical fu nction, but did not affect coronary flow in the pre-ischemic heart. Di lazep at 5 or 10 mu M accelerated the recovery of mechanical function and coronary flow during reperfusion, and it attenuated metabolic chan ges induced by ischemia and reperfusion. Dilazep at 1 mu M neither dec reased the pre-ischemic mechanical function nor restored the mechanica l function during reperfusion, although it attenuated the accumulation of free fatty acids during reperfusion. These results suggest that di lazep attenuates both ischemia- and reperfusion-induced myocardial dam age and that the anti-ischemic action of dilazep is not due to coronar y vasodilation but probably due to an energy-sparing effect and other effects that remain to be studied.