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 mu mol/kg+1.4 mu mol/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 mu mol/kg+4.8 mu mol/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.