MALIGNANT ARRHYTHMIAS AND ACUTE MYOCARDIAL-ISCHEMIA - INTERACTION BETWEEN FLECAINIDE AND THE AUTONOMIC NERVOUS-SYSTEM

The antiarrhythmic and proarrhythmic effects of flecainide were assess ed in 21 anesthetized cats. Ventricular arrhythmias can be reproducibl y induced in cats by the combination of acute myocardial ischemia and sympathetic stimulation. Premature ventricular contractions (PVCs), su stained (sVT) and nonsustained (nsVT) ventricular tachycardia (VT), or ventricular fibrillation IVF) may be induced by a I-minute left stell ate ganglion stimulation during a and minute coronary artery occlusion . After three trials yielding consistent results, flecainide (2 mg/kg intravenous bolus plus 2 mg kg(-1) hr(-1) intravenous infusion) was in jected and two additional trials performed. Eight cats also underwent two trials after propranolol (0.2 mg/kg) administered while flecainide infusion was maintained. Flecainide decreased heart rate and blood pr essure and slightly prolonged JTc (9%, p < 0.05). It markedly augmente d QRS duration (61%, p < 0.0001), which was increased by an additional 61% (p < 0.0001) during sympathetic stimulation. VF was observed in 8 animals and never after flecainide (p < 0.05). However, after drug ad ministration all cats had VT (2 nsVT and 6 sVT), and 5 required cardia c massage. Flecainide did not prevent the occurrence of nsVT in 6 cats , and it worsened arrhythmias by inducing VT (rt nsVT and 2 sVT) in 6 cats with only PVCs or without arrhythmias in the control trials. Prop ranolol, administered while flecainide infusion was maintained, preven ted the increase in heart rate and the marked QRS prolongation during sympathetic stimulation (4 +/- 3 vs 52 +/- 16 msec, p < 0.05) and abol ished the proarrhythmic effect of flecainide in 4 of 5 animals. Thus f lecainide, despite an antifibrillatory effect, does not prevent and ac tually may favor the occurrence of sVT during acute myocardial ischemi a and enhanced sympathetic activity. Propranolol, by countering the in crease in heart rate during sympathetic stimulation, prevented the rat e-dependent conduction delay and abolished the proarrhythmic effect of flecainide. The exacerbation, whenever a transient ischemic episode i s accompanied by elevated sympathetic activity, of the ischemia-induce d conduction delay caused by flecainide may in part explain the mortal ity data in the Cardiac Arrhythmia Suppression Trial.