Anisotropic effects of sodium channel blockers on the wavelength for ventricular excitation in dogs.
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.
Watanabe
T
T
First Department of Internal Medicine, Yamagata University School of Medicine, Japan. tewatana@med.id.yamagata-u.ac.jp
Yamaki
M
M
Tachibana
H
H
Yamauchi
S
S
Kubota
I
I
Tomoike
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000188:drug therapy; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D005424:Flecainide / Q000009:adverse effects; D006329:Heart Conduction System / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000188:drug therapy; D014693:Ventricular Fibrillation / Q000188:drug therapy; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D008012:Lidocaine; D004206:Disopyramide; D005424:Flecainide