Effects of flecainide on ventricular arrhythmias, abnormal automaticity and activation in a canine model of myocardial infarction.
Effects of flecainide, a class I antiarrhythmic drug, on ventricular arrhythmias, ventricular abnormal automaticity and ventricular activation were examined in a canine model of myocardial infarction, and compared with those of lidocaine. The effects of the drugs were examined on (1) the arrhythmias developed 24 h after the left anterior descending coronary artery (LAD) ligation, (2) ventricular premature stimulation-induced arrhythmias 5 to 7 d after LAD ligation, (3) ventricular abnormal automaticity about 24 h after LAD ligation and (4) ventricular activation induced by a ventricular stimulation at various coupling intervals in animals 5 to 7 d after LAD ligation. Flecainide (1 and 3 mg/kg) showed a marked reduction in the frequency of ventricular ectopic beats 24 h after LAD ligation, and was more potent than lidocaine. The ventricular abnormal automaticity was inhibited by flecainide (1 and 3 mg/kg) and lidocaine (10 mg/kg). Flecainide (1 and 3 mg/kg) prolonged the activation time in the infarcted zones over a wide range of the coupling intervals, and produced block of seriously delayed activation. In contrast, lidocaine produced similar effects only at short coupling intervals. Ventricular premature stimulation produced ventricular arrhythmias, which were prevented by pretreatment with flecainide (3 mg/kg). In conclusion, flecainide showed antiarrhythmic effects in a canine model of myocardial infarction. A marked inhibition of ventricular abnormal automaticity and selective depression of delayed activation in the infarcted zone probably contribute to its antiarrhythmic effect.
Hashimoto
H
H
Fujinomiya City General Hospital, Japan.
Katoh
H
H
Nakashima
M
M
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005424:Flecainide / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D007275:Injections, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D009203:Myocardial Infarction / Q000503:physiopathology*
D008012:Lidocaine; D005424:Flecainide