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.
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.
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications; D001552:Benzazepines / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003864:Depression, Chemical; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology
D001552:Benzazepines; D009599:Nitroprusside; D011433:Propranolol; D004110:Diltiazem; D000241:Adenosine