Effects of diltiazem upon experimental ventricular dysrhythmias

E Patterson, BT Eller and BR Lucchesi

The antidysrhythmic and antifibrillatory actions of the calcium entry blocker diltiazem were examined in three experimental canine models: 1) ventricular fibrillation thresholds in the anesthetized dog; 2) programmed electrical stimulation in the conscious dog during the subacute phase of myocardial infarction; and 3) a conscious canine model of sudden coronary death wherein ventricular fibrillation was produced by acute myocardial ischemia in the presence of previous anterior myocardial infarction. Diltiazem administration failed to alter ventricular fibrillation thresholds determined under normal physiologic conditions and during acute occlusion of the distal left anterior descending coronary artery. Diltiazem did not prevent ventricular tachyarrhythmias produced by programmed electrical stimulation in the subacute phase of myocardial infarction. The coupling intervals of premature beats producing ventricular tachycardia and the cycle length of the ventricular tachycardias were unchanged by diltiazem administration. In a conscious canine model of sudden coronary death, left circumflex coronary artery thrombosis was produced in the presence of previous anterior myocardial infarction. Acute myocardial ischemia as evidenced by ST-segment changes in saline- treated animals (145 +/- 26 min) was followed by the development of premature ventricular beats (150 +/- 27 min) and ventricular tachycardia (154 +/- 26 min). Ventricular fibrillation occurred in 9 of 10 animals at 156 +/- 28 min. Diltiazem administration did not affect the time to development of ST-segment changes (196 +/- 38 min), premature ventricular beats (202 +/- 37 min) or ventricular tachycardia (209 +/- 37 min). Although the development of ventricular fibrillation was not prevented by diltiazem (9 of 10 animals developed ventricular fibrillation), the time to onset of the fatal arrhythmia was delayed significantly (P less than .01). These data fail to suggest a protective action for the calcium entry blocker diltiazem.

Volume 225, Issue 1, pp. 224-233, 04/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics