Verapamil and tiapamil in prevention of ventricular fibrillation in pigs with coronary ligation. Comparative effects on left ventricular function.

Abstract

Antiarrhythmic and hemodynamic effects of the calcium channel antagonist verapamil were compared with those of tiapamil, a congener, in open-chest pigs with anterior descending coronary artery ligation. Tiapamil (6 mg/kg i.v.) decreased the incidence of ventricular fibrillation to 4 of 10 versus 22 of 25 in controls (p less than 0.05) and maintained left ventricular dP/dtmax after ligation (predrug value: 2,312 +/- 112 mm Hg/sec; 20 minutes after ligation: 2,139 +/- 229 mm Hg/sec). Tiapamil increased blood flow in the peripheral ischemic zone (24 +/- 3.2% vs. 16.9 +/- 1.6% of preligation value in controls, p less than 0.05) as well as in the peri-ischemic and nonischemic zones (153.9 +/- 12.7% and 186.3 +/- 17.1%, respectively; both p less than 0.0001 vs. 97.9 +/- 5% and 91.3 +/- 4.7% in controls). Verapamil (0.6 mg/kg i.v.) decreased the incidence of ventricular fibrillation to 0 of 7 versus 22 of 25 in controls (p less than 0.005); left ventricular dP/dtmax decreased from 2,062 +/- 144 to 1,060 +/- 168 mm Hg/sec (p less than 0.0001). Verapamil did not change blood flow in the peripheral, peri-ischemic, or nonischemic zones. Thus, tiapamil, and not verapamil, decreased ischemic ventricular fibrillation while maintaining left ventricular mechanical function. Verapamil congeners warrant further evaluation as antiarrhythmic agents in acute myocardial ischemia.