Electrophysiological effects of flecainide in a canine 7 day old myocardial infarction model.
Flecainide has been reported to be effective in suppressing chronic ventricular arrhythmias in clinical studies, but the electrophysiological mechanisms of its action are not understood. We therefore studied its effects on re-entrant ventricular arrhythmias in eight dogs with 7 day old infarction. Epicardial mapping and local refractory periods were obtained using 48 channel bipolar electrodes attached to the epicardium. Epicardial conduction velocity was significantly depressed by flecainide (2 mg.kg-1 intravenously), from 49.3 (SD 11.9) cms-1 to 35.3(11.2) cm s-1 (p less than 0.01). Flecainide prolonged effective refractory periods (ERP) in the normal, border and infarct zones: normal (n = 93), from 189.5 (15.9) to 219.3 (17.7) ms, p less than 0.01; border (n = 54) from 187.4(24.0) to 225.2 +/- 32.5 ms, p less than 0.01; and infarct (n = 93), from 197.7 (30.6) to 247.1 (34.2) ms, p less than 0.01. However, the percent change in refractoriness was greater in the infarct zone than in the normal zone, at 25.7(17.1)% v 16.2 (10.3)%, p less than 0.01. Furthermore, an area of functional unidirectional conduction block developed within the infarct zone where the maximal dispersion of ERP was observed. Inducible sustained ventricular tachycardia (SVT) was prevented in one dog and slowed (300 to 150 beats.min-1) in another by flecainide, while ventricular fibrillation remained inducible in one dog. Pro-arrhythmic effects were observed in two of five dogs without inducible SVT. In conclusion, flecainide significantly depressed conduction velocity and prolonged local refractoriness in the epicardial myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Sakai
T
T
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Ogawa
S
S
Hosokawa
M
M
Miyazaki
T
T
Sakurai
K
K
Nakamura
Y
Y
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D005424:Flecainide / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects; D006352:Heart Ventricles; D009203:Myocardial Infarction / Q000150:complications*; D012032:Refractory Period, Electrophysiological
D005424:Flecainide