Evaluation of the timing of flecainide administration and ischemia-induced ventricular arrhythmias in rats

Abstract

Ischemia-induced arrhythmias are major complications of acute myocardial infarction; therefore, understanding the proper use of antiarrhythmic drugs in this situation is important. The goal of the present study was to determine how the timing of flecainide administration influenced ischemia-induced arrhythmias in an isolated rat heart model. Ischemia-induced arrhythmia was produced by ligating the left coronary artery. The effect of flecainide (10 −6 M) on ischemia-induced arrhythmia varied depending on the time of drug administration in relation to the time of coronary artery ligation. Drug administration both before and after (group 5) coronary artery ligation was most effective, followed by administration before (group 4) and then by administration after (group 3). At the end of each experiment, the left and right ventricular walls of each heart were separated, and drug concentration in each part was measured. Drug concentration in the left ventricular wall differed significantly between the group in which coronary artery ligation was not performed (group 1) and group 3 or 4. No correlation between drug concentration in the right ventricular wall and antiarrhythmic effect was observed. These differences in antiarrhythmic effect depending on the timing of drug administration may be caused by the difference in drug concentration in the ischemic zone and the effect of coronary artery occlusion on the speed of drug dispersion within this zone. This myocardial infarction model is useful for studying the correlation between antiarrhythmic effect and regional drug distribution.