Document Detail


Postrepolarization refractoriness as a potential anti-atrial fibrillation mechanism of pilsicainide, a pure sodium channel blocker with slow recovery kinetics.
MedLine Citation:
PMID:  9926279     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 refractoriness, even at rapid stimulation rates, thus exerting a salutary antifibrillatory effect.
Authors:
H Kanki; H Mitamura; S Takatsuki; K Sueyoshi; K Shinagawa; T Sato; S Ogawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy     Volume:  12     ISSN:  0920-3206     ISO Abbreviation:  Cardiovasc Drugs Ther     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1999-03-30     Completed Date:  1999-03-30     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  8712220     Medline TA:  Cardiovasc Drugs Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  475-82     Citation Subset:  IM    
Affiliation:
Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects
Animals
Anti-Arrhythmia Agents / therapeutic use*
Atrial Fibrillation / drug therapy*
Dogs
Drug Evaluation, Preclinical
Female
Kinetics
Lidocaine / analogs & derivatives*,  therapeutic use
Male
Sodium Channel Blockers*
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Sodium Channel Blockers; 137-58-6/Lidocaine; 88069-49-2/pilsicainide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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