Low doses of ranolazine and dronedarone in combination exert potent protection against atrial fibrillation and vulnerability to ventricular arrhythmias during acute myocardial ischemia

Abstract

Background: Coronary artery disease carries dual risk for atrial tachyarrhythmias and sudden cardiac death. Objective: To examine whether low-dose ranolazine and/or dronedarone can protect against vulnerability to atrial fibrillation (AF) and ventricular tachyarrhythmias. Methods: In chloralose-anesthetized, open-chest Yorkshire pigs (n = 15), the proximal segment of left circumflex (LCx) coronary artery was occluded to reduce flow by 75%. An electrode catheter was positioned on the left atrial appendage to measure AF threshold (AFT) before and during LCx coronary artery stenosis before and at 1 hour after dronedarone (0.5 mg/kg intravenous bolus over 5 minutes) and/or ranolazine administration (0.6 mg/kg intravenous bolus followed by 0.035 mg/kg/min). Results: Before drug administration, LCx coronary artery stenosis lowered AFT from 25.2±1.7 mA control (mean±SEM) to 4.9±1.0 mA baseline (P