Quinidine and flecainide increased the Vl/Vt ratio of anisotropic conduction in isolated porcine hearts, whereas cibenzoline decreased the Vl/Vt ratio.
Do quinidine, flecainide, and cibenzoline have differential effects on anisotropic conduction in isolated porcine hearts?
Class I antiarrhythmic drugs exhibit different orientation-dependent effects on anisotropic conduction, which may influence their therapeutic efficacy or proarrhythmic potential.
INTRODUCTION: Anisotropic conduction characteristics, expressed as the ratio of conduction velocities in the longitudinal (Vl) and transverse (Vt) fiber directions, may play a role in the mechanism of some ventricular tachycardias and is influenced by pharmacologic interventions. Discrepancies exist among the reported orientation-dependent effects of available Class I antiarrhythmic drugs. The aim of this study was to assess the respective effects of quinidine (Class IA), flecainide (Class IC), and cibenzoline (not subclassified) on the anisotropic conduction of porcine hearts, in corroboration of their effects on ventricular action potentials. METHODS AND RESULTS: We studied the actions of 3 and 10 microM quinidine, 1 and 3 microM flecainide, and 0.3 and 1 microM cibenzoline on Vl and Vt determined from 128 electrograms recorded with a plaque electrode on the anterior left ventricle of isolated perfused hearts (spacing 2.5 mm). Vl and Vt were computed from isochronal maps displaying ellipsoid activation during stimulation from the center of the plaque. The effects on the maximal rate of depolarization (Vmax) of action potentials were obtained from ventricular muscle exposed to the same drugs. Flecainide 1 microM and cibenzoline 0.3 microM did not alter Vl and Vt significantly. Quinidine 3 microM predominantly depressed Vl at rapid pacing rates, but the Vl/Vt ratio was not significantly altered. Quinidine 10 microM and flecainide 3 microM reduced Vl and Vt in a frequency-dependent fashion. Conversely, cibenzoline 1 microM mostly decreased Vl and thus decreased the Vl/Vt ratio and increased the Vl/Vt at all pacing rates. This different effect was not related to a greater depressant effect on Vmax CONCLUSION: Quinidine and flecainide act similarly on the anisotropic pattern of conduction (both drugs increase the Vl/Vt ratio), whereas cibenzoline exerts opposite effects. Orientation-dependent effects are different among Class I antiarrhythmic drugs and may be of importance in their therapeutic efficacy or proarrhythmic potential.
Lacroix et al. (1998) studied Anisotropic conduction in isolated porcine heart. Quinidine, flecainide, and cibenzoline was evaluated on Longitudinal (Vl) and transverse (Vt) conduction velocities and Vl/Vt ratio. Quinidine and flecainide increased the Vl/Vt ratio of anisotropic conduction in isolated porcine hearts, whereas cibenzoline decreased the Vl/Vt ratio.