Key result
Intracoronary flecainide shortened the wavelength for ventricular excitation in the longitudinal direction and induced ventricular fibrillation in 3 of 6 dogs, unlike disopyramide or lidocaine.
Why the study?
Do sodium channel blockers have anisotropic effects on wavelength for ventricular excitation and proarrhythmia in dogs?
Do sodium channel blockers have anisotropic effects on wavelength for ventricular excitation and proarrhythmia in dogs?
Flecainide causes anisotropic shortening of the wavelength for ventricular excitation, providing a potential mechanism for its observed proarrhythmic effects.
May explain flecainide proarrhythmia via anisotropic effects; leaves open translation to human ventricular arrhythmias.
The purpose of this study was to determine the anisotropic effects of sodium channel blockers on wavelength (WL) and proarrhythmia. In 18 anesthetized, open chest dogs, a 64-electrode array was placed on the left ventricle and the ventricle was constantly paced. Disopyramide, lidocaine or flecainide was intracoronarily administered. Conduction velocity (theta) and activation-recovery interval (ARI) were measured in the longitudinal (L) and transverse (T) directions. Flecainide markedly decreased thetaL, but did not alter thetaT or ARIs in either direction. As a result, the wavelength was significantly shortened only in the L direction. Disopyramide or lidocaine did not show direction-dependent effects on theta or WL. In 3 of 6 dogs with flecainide exposure, ventricular fibrillation (VF) developed. However, no VF occurred with disopyramide or lidocaine. Accordingly, the WL is dependent on the fiber orientation of myocardium. The anisotropic shortening of the WL may explain the character of the proarrhythmia observed with flecainide.
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Watanabe et al. (2000) studied this question. Sodium channel blockers (Disopyramide, lidocaine, or flecainide) vs. Other sodium channel blockers was evaluated on Conduction velocity, activation-recovery interval, wavelength, and proarrhythmia (ventricular fibrillation). Intracoronary flecainide shortened the wavelength for ventricular excitation in the longitudinal direction and induced ventricular fibrillation in 3 of 6 dogs, unlike disopyramide or lidocaine.
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