Inhibiting Effect of Amiodarone to Protective Action against Ischemia/Reperfusion Injury Induced by Ischemic Preconditioning

Abstract

Background: Ischemic preconditioning (IPC) has protective effects on myocardial ischemia. These effects may be caused by ATP (adenosine triphosphate) sensitive potassium () channel activation. Amiodarone also has pharmacologic preconditioning effects, especially suppression of reperfusion arrhythmia. The mechanisms of amiodarone effects are different from that of IPC. The aim of this study using the isolated rat working heart was 1) to confirm whether IPC and amiodarone protected against reperfusion injury; and, if so, 2) to example whether combination of IPC and amiodarone demonstrated additive effect or not. Methods: Isolated rat hearts were stabilized for 30 minutes and were subdivided into four groups. Control group was subjected low-flow ischemia of 5% dextrose water for 30 minutes. IPC group was pretreated with IPC. In Amiodarone group, whole process was same as control group except amiodarone administration during low-flow ischemia. Amiodarone-IPC group, IPC was applied and also administrated amiodarone. Isovolumetric left ventricular end systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP), dP/ and heart rate were measured. Results: Group II showed more recovered LVESP, less developed ventricular stiffness, more preserved coronary effluent flow, earlier termination of arrhythmia and smaller infarct size than Group I. Group III showed preserved LVESP and dP/, less developed ventricular stiffness, shortest arrhythmia sustaining time, smallest infarct size among all groups. These myocardial protective effects were abolished in Group IV. Conclusions: We observed that IPC and amiodarone administration, each has myocardial protective effects against myocardial ischemia, but when they are dealt at the same time, their beneficial effects diminished.