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Postrepolarization Refractoriness as a Potential Anti–Atrial Fibrillation Mechanism of Pilsicainide, a Pure Sodium Channel Blocker with Slow Recovery Kinetics

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Abstract

The antifibrillatory effect of pilsicainide, a sodium channel blocker with slow recovery kinetics, was investigated in a canine model of atrial fibrillation. Prolonging the atrial effective refractory period is an important mechanism for pharmacological termination of atrial fibrillation. However, the effectiveness of potassium channel blockers has been questioned because of their reverse-use–dependent property. In eight open-chest dogs, the duration of the atrial endocardial monophasic action potential and the atrial effective refractory period were determined using a Franz catheter. Conduction velocity was obtained from a 96-channel mapping electrode at multiple cycle lengths. Inducibility of sustained atrial fibrillation (>30 minutes) was confirmed by atrial burst pacing during bilateral vagal stimulation, and local fibrillation cycle lengths were measured. Five minutes after restarting fibrillation, pilsicainide (0.6 mg/kg + 0.04 mg/kg/min) was administered. After fibrillation was terminated, measurements were repeated. Pilsicainide successfully terminated atrial fibrillation in 7 of 8 dogs after the median time of 5.1 minutes. The conduction velocity decreased significantly. Although pilsicainide did not affect monophasic action potential duration, it caused use-dependent prolongation of the atrial effective refractory period (P < 0.05), creating postrepolarization refractoriness. Accordingly, pilsicainide prolonged the atrial fibrillation cycle length from 80.6 to 113.8 ms (P < 0.05) before termination of fibrillation. Sodium channel blockers with slow recovery kinetics can prolong the atrial effective refractory period without affecting monophasic action potential duration. Unlike potassium channel blockers, these sodium channel blockers maintain postrepolarization refract

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Authors and Affiliations

  1. Cardiopulmonary Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Hideaki Kanki, Hideo Mitamura, Seiji Takatsuki, Kouichiro Sueyoshi, Kaori Shinagawa, Toshiaki Sato & Satoshi Ogawa

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  1. Hideaki Kanki
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  2. Hideo Mitamura
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  3. Seiji Takatsuki
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  4. Kouichiro Sueyoshi
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  5. Kaori Shinagawa
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  7. Satoshi Ogawa
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Kanki, H., Mitamura, H., Takatsuki, S. et al. Postrepolarization Refractoriness as a Potential Anti–Atrial Fibrillation Mechanism of Pilsicainide, a Pure Sodium Channel Blocker with Slow Recovery Kinetics. Cardiovasc Drugs Ther 12, 475–482 (1998). https://doi.org/10.1023/A:1007758217189

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