title: Anti-atrial Fibrillatory Versus Proarrhythmic Potentials of Amiodarone: A New Protocol for Safety Evaluation In Vivo.
abstract: Anti-atrial fibrillatory and proarrhythmic potentials of amiodarone were simultaneously analyzed by using the halothane-anesthetized beagle dogs (n = 4) in order to begin to prepare standard protocol for clarifying both efficacy and adverse effects of anti-atrial fibrillatory drugs. Intravenous administration of 0.3 mg/kg of amiodarone hydrochloride decreased the heart rate and mean blood pressure. Additional administration of 3 mg/kg of amiodarone hydrochloride prolonged the QT interval besides the effects observed by the low dose, whereas it showed 1.6 times larger prolongation in the effective refractory period of the atrium than that of the ventricle, which may explain its clinical efficacy against atrial arrhythmias. However, no significant change was detected by either dose in the early repolarization assessed by corrected J-Tpeakor the late repolarization done by Tpeak-Tendin the electrocardiogram, although the former tended to be shortened and the reverse was true for the latter. Lack of prolongation in the early repolarization will make it feasible to better understand why amiodarone lacks proarrhythmic potential in spite of the QT-interval prolongation. Thus, these results of amiodarone obtained by current protocol may become a guidance on assessing efficacy and adverse effects of new anti-atrial fibrillatory drugs in vivo.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
authors.forename: Suchitra
authors.initials: S
authors.lastname: Matsukura
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wada
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Izumi-Nakaseko
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan. atsushi.sugiyama@med.toho-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
mesh_terms: D000200:Action Potentials; D000638:Amiodarone / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000633:toxicity*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D012032:Refractory Period, Electrophysiological; D018570:Risk Assessment; D013997:Time Factors; D016171:Torsades de Pointes / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D000638:Amiodarone
keywords: Amiodarone; Atrial fibrillation; Bepridil; Early repolarization; Effective refractory period; QT interval; Torsade de pointes; dl-Sotalol