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

The effects of short-term amiodarone and dronedarone treatments on action potential characteristics and arrhythmia (ventricular tachycardia) induced by reperfusion after global low-flow ischemia were studied in rat hearts. The 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 coronary flow, 0.3 ml/min) followed by 30 min of reperfusion at constant pressure. Drugs were applied only during ischemia: consequently, action potential duration (APD) tended to widen. During reperfusion, APD tended to recover or shorten, and the more complete the recovery, the less the arrhythmia. Despite its ability to widen APD during ischemia, amiodarone facilitated APD recovery during reperfusion. Moreover, APD shortening and ventricular tachycardia suppression exhibit a bell-shaped concentration-response relation, implying that the drugs affect ventricular tachycardia by a class III-independent action. These results point to an anti-ischemic action supported by improvement in function and inhibition of reactive hyperemia.