Beneficial effects of amiodarone and dronedarone (SR 33589b), when appliedduring low-flow ischemia, on arrhythmia and functional parameters assessedduring reperfusion in isolated rat hearts

The effects of short-term amiodarone and dronedarone treatments on action p otential characteristics and arrhythmia (ventricular tachycardia) induced b y reperfusion after global low-flow ischemia were studied in rat hearts. Th e actions of amiodarone and SR on recovery of coronary flow and contractile function were also determined. Isolated hearts were stabilized for 40 min and were then submitted to 25-min global low-flow ischemia (constant corona ry flow, 0.3 ml/min) followed by 30 min of reperfusion at constant pressure . Drugs were applied only during ischemia: consequently, action potential d uration (APD) tended to widen. During reperfusion, APD tended to recover or shorten, and the more complete the recovery, the less the arrhythmia. Desp ite its ability to widen APD during ischemia, amiodarone facilitated APD re covery during reperfusion. Moreover, APD shortening and ventricular tachyca rdia suppression exhibit a bell-shaped concentration-response relation, imp lying that the drugs affect ventricular tachycardia by a class III-independ ent action. These results point to an anti-ischemic action supported by imp rovement in function and inhibition of reactive hyperemia.