title: Beat-to-beat variability of repolarization differentiates the extent of torsadogenic potential of multi ion channel-blockers bepridil and amiodarone.
abstract: Bepridil and amiodarone are known to have a multiple ion channel-blocking property in the heart. In this study, we compared the effects of bepridil on beat-to-beat variability of repolarization, a new predictive marker of torsades de pointes arrhythmia, with those of amiodarone. Bepridil (30 mg/kg, n=4) or amiodarone (200 mg/day for initial 7 days and 100 mg/day for following 21 days, n=4) was orally administered to chronic atrioventricular block dogs under the Holter ECG monitoring. The QT interval was prolonged after the administration of bepridil and amiodarone, and torsades de pointes arrhythmia was induced in 3 out of 4 dogs after the bepridil administration, which was not observed during the chronic administration of amiodarone. Beat-to-beat variability of repolarization, quantified as the short-term variability of the QT interval, increased after the administration of bepridil by +3.0 ms, whereas no significant change was detected in this parameter after the administration of amiodarone. These results suggest that the beat-to-beat variability of repolarization is a useful marker for differentiating the extent of torsadogenic potential of multi ion channel-blockers bepridil and amiodarone.
authors.affiliation: Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takahara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
mesh_terms: D000638:Amiodarone / Q000009:adverse effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D054537:Atrioventricular Block / Q000188:drug therapy / Q000503:physiopathology; D015764:Bepridil / Q000009:adverse effects*; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008297:Male; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D015764:Bepridil; D000638:Amiodarone