Prevention of Class III‐Induced Proarrhythmias by Flecainide in an Animal Model of the Acquired Long QT Syndrome

The influence of the class Ic agent, flecainide, on the incidence of class III-induced torsades de pointes was examined in an animal model of the acquired long QT syndrome. Twenty-four chloralose-anaesthetized rabbits were pretreated at random with flecainide or vehicle and subsequently given a concomitant infusion of methoxamine and the class III antiarrhythmic agent almokalant. In seven out of eight vehicle-treated rabbits, almokalant induced torsades de pointes which was preceded by a significant lengthening of the JTU interval (used as an indirect measure of ventricular repolarization time) by 55 +/- 9.2 msec. Flecainide dose-dependently reduced the incidence of almokalant-induced torsades de pointes. Hence, in a group of rabbits given a low dose (0.14 mumol/kg + 1.4 mumol/kg/hr) of flecainide, four out of eight animals experienced torsades de pointes (P = 0.1538 versus vehicle) whereas no case (n = 8) was observed after a higher dose (4.8 mumol/kg + 4.8 mumol/kg/hr, P = 0.0007). In the former group almokalant induced a maximal increase in the JTU interval not differing from that seen in the vehicle-treated group (58 + 12.1 msec, P > 0.05). Pretreatment with the high dose of flecainide, however, caused a significant attenuation of the almokalant-induced lengthening of the JTU interval (18 +/- 6.5 msec. P < 0.05). It is concluded that flecainide reduces the risk of proarrhythmia in the setting of delayed repolarization partially by attenuating the primary electrophysiological effect of class III agents.