Effect of dilazep on myocardial contractility following acute ischemia and reperfusion in isolated blood-perfused canine left ventricular muscle.
Myocardial protection by dilazep HCl, an antianginal drug and a potent calcium antagonist, against myocardial damage following acute ischemia and reperfusion was studied with respect to myocardial contractility in isolated blood-perfused canine left ventricular muscle. Myocardial function was expressed by percent recovery rate of maximal net developed tension. 1) The coronary infusion of dilazep revealed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. 2) The intravenous administration of dilazep to the support dog and Young's infusion also showed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. Dilazep showed no persistent depression of myocardial contractility due to its calcium antagonistic effect during reperfusion. 3) The combination of intravenous administration of dilazep to the support dog, Young's infusion, and hypothermia showed significant myocardial protection during prolonged ischemia and reperfusion even in hypertrophied ventricle. These results demonstrate that dilazep provides effective myocardial protection during ischemic arrest and reperfusion by preventing abnormal calcium accumulation in myocardial cells during reperfusion. No persistent depression of myocardial contractility during reperfusion may support dilazep's clinical application as a myocardial protective agent in open-heart surgery.
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis / Q000037:antagonists & inhibitors; D006332:Cardiomegaly / Q000503:physiopathology; D003327:Coronary Disease / Q000503:physiopathology*; D004109:Dilazep / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000032:analysis; D010477:Perfusion
D001381:Azepines; D004109:Dilazep; D002118:Calcium