Studies on mechanisms of diltiazem-induced protection of the ischemic myocardium: selective myocardial depressant action of diltiazem on an ischemic isolated blood-perfused canine papillary muscle preparation

JH Ngai, Y Yabuuchi, A Schwartz and RW Millard

The effect of diltiazem on the contractile and vascular responses to 2 min of total occlusion and reperfusion was investigated in isolated blood-perfused canine papillary muscle preparations. Diltiazem, in doses (3 and 10 micrograms/min) that increased coronary blood flow but did not change developed tension and maximum rate of tension development (dT/dt) in papillary muscle before occlusion, attenuated tension development between 40 and 120 sec of ischemia. At-60 sec postocclusion, developed tension was at 36 +/- 4, 37 +/- 5 and 44 +/- 4% below preocclusion levels for 3, 10 and 100 micrograms/min of diltiazem, respectively (nondiltiazem treated = 24 +/- 3%). The dT/dt increased to 22 +/- 6% above preocclusion value during ischemia in nondiltiazem-treated preparations. This was blocked by diltiazem in a dose-dependent fashion. Propranolol and nitroprusside did not modify the developed tension and the increase in dT/dt of the papillary muscle during occlusion. On reperfusion, an overshoot in developed tension to 22 +/- 4% above preocclusion level was observed. This was significantly reduced by diltiazem and propranolol but not by nitroprusside. Diltiazem inhibited the maximal peak reactive hyperemia response after 2 min of occlusion by 30 to 38%. Both propranolol and nitroprusside did not change this response. The results show that diltiazem selectively depresses the inotropic state of the ischemic myocardium and suggest that a diltiazem-induced reduction in myocardial oxygen consumption during ischemia may contribute to the protection of ischemic myocardium and the reduction in reactive hypermia response in the ischemic heart.

Volume 225, Issue 2, pp. 462-469, 05/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics