Published Online
on February 3, 2003

A more recent version of this article appeared on February 18, 2003

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Submitted on August 8, 2002
Revised on November 5, 2002
Accepted on November 6, 2002

Widening of the Excitable Gap and Enlargement of the Core of Reentry During Atrial Fibrillation With a Pure Sodium Channel Blocker in Canine Atria

Ayaka Kawase MD, Takanori Ikeda MD^*, Kazuo Nakazawa PhD, Takashi Ashihara MD, Tsunetoyo Namba MD, Tetsuya Kubota MD, Kaoru Sugi MD, and Hironori Hirai MD

From the Third Department of Internal Medicine, Toho University School of Medicine, Tokyo (A.K., T.I., T.K., K.S., H.H.), and the Working Group on Cardiac Simulation and Mapping (K.N., T.A., T.N.), Tokyo, Japan.

^* To whom correspondence should be addressed. E-mail: iket{at}kyorin-u.ac.jp.

Background--This study aimed to assess the effects of pilsicainide, a pure sodium channel blocker, on electrophysiological action and wavefront dynamics during atrial fibrillation (AF).

Methods and Results--In a newly developed model of isolated, perfused, and superfused canine atria (n=12), the right and left endocardia were mapped simultaneously by use of a computerized mapping system. AF was induced with 1 to 5 µmol/L acetylcholine. The antifibrillatory actions of pilsicainide on AF cycle length (AFCL), refractory period (RP), conduction velocity (CV), excitable gap (EG), and the core of the mother rotor were studied. The RP was defined as the shortest coupling interval that could capture the fibrillating atrium. The EG was estimated as the difference between the AFCL and RP. At baseline, multiple wavefronts were observed. After 2.5 µg/mL infusion of pilsicainide, all preparations showed irregular activity, and AF was terminated in 2 preparations. The AFCL and RP were prolonged, and CV was decreased significantly. The EG was widened (147%; P<0.01), and the core perimeter was increased (100%; P<0.01). Increasing the dosage either terminated AF (6 preparations) or converted to organized activity (ie, atypical atrial flutter) (4 preparations). On the maps, all "unorganized" AFs were terminated with the excitation of the core of the mother rotor by an outside wavefront, whereas in preparations with atrial flutter, pilsicainide did not terminate its activity.

Conclusions--Widening of the EG by pilsicainide facilitates the excitation of the core of the mother rotor, leading to the termination of AF. In some experiments, pilsicainide converts AF to persistent atrial flutter.

Key words: atrial fibrillation • mapping • sodium channel blockers • pilsicainide • excitable gap

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