Electrophysiologic effects of sodium channel blockade on anisotropic conduction and conduction block in canine myocardium: preferential slowing of longitudinal conduction by flecainide versus disopyramide or lidocaine.
OBJECTIVE
The purpose of this study was to determine the effects of sodium channel blockade on anisotropic excitation propagation in the intact canine left ventricle.


BACKGROUND
Anisotropic ventricular conduction- electric conductivity dependent on the myocardial fiber direction-is one of the important mechanisms of ventricular arrhythmia. However, the effects of sodium channel blockade, especially the differential effect of a subclass of this agent, on the anisotropic properties remain unknown.


METHODS
In 28 anesthetized, open chest dogs, a small cannula was inserted into the left anterior descending coronary artery. Saline (control), disopyramide, lidocaine or flecainide was infused selectively into the cannula. An array of 64 epicardial electrodes was placed on the anterior surface of the ventricle. Activation time (AT) was measured along the longitudinal (L) and transverse (T) directions.


RESULTS
High dose flecainide (100 microg/kg body weight per min) delayed the AT along the L direction markedly (mean [+/-SE] 227 +/- 38%, p < 0.02) and mildly (121 +/- 10%, p < 0.02) along the T direction in regular beats (p < 0.007, L vs. T). Lidocaine and disopyramide did not show direction-dependent prolongation of the AT on regular beats. When examined on premature beats, AT was delayed, depending on the coupling interval and the fiber direction when saline, flecainide or lidocaine was infused. The conduction blocks along the L direction were observed in three of seven dogs on regular beats after flecainide and ventricular fibrillation ensued in two of these three dogs.


CONCLUSIONS
A peculiar slowing of L conduction by flecainide may relate to the character of proarrhythmia.
Kondo
T
T
First Department of Internal Medicine, Yamagata University School of Medicine, Iida-Nishi, Japan.
Yamaki
M
M
Kubota
I
I
Tachibana
H
H
Tomoike
H
H
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D005117:Cardiac Complexes, Premature / Q000503:physiopathology; D004206:Disopyramide / Q000494:pharmacology*; D004285:Dogs; D004553:Electric Conductivity; D004594:Electrophysiology; D005424:Flecainide / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects*; D006352:Heart Ventricles / Q000294:innervation*; D008012:Lidocaine / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; D008012:Lidocaine; D004206:Disopyramide; D005424:Flecainide