Anti-atrial Fibrillatory Versus Proarrhythmic Potentials of Amiodarone: A New Protocol for Safety Evaluation In Vivo

• Published in: Cardiovascular toxicology Vol. 17; no. 2; pp. 157 - 162
• Main Authors: Matsukura, Suchitra, Nakamura, Yuji, Cao, Xin, Wada, Takeshi, Izumi-Nakaseko, Hiroko, Ando, Kentaro, Sugiyama, Atsushi
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2017; Springer; Springer Nature B.V
• Subjects: Action Potentials; Amiodarone; Amiodarone - pharmacology; Amiodarone - toxicity; Animals; Anti-Arrhythmia Agents - pharmacology; Anti-Arrhythmia Agents - toxicity; Arrhythmia; Atrial Fibrillation - diagnosis; Atrial Fibrillation - drug therapy; Atrial Fibrillation - physiopathology; Bepridil; Biomedical and Life Sciences; Biomedicine; Blood Pressure - drug effects; Cardiac Pacing, Artificial; Cardiology; Catheters; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Drug dosages; Electrocardiogram; Electrocardiography; Electrodes; Female; Halothane; Heart beat; Heart rate; Heart Rate - drug effects; Laboratory animals; Male; Pharmaceutical industry; Pharmacology/Toxicology; Refractory Period, Electrophysiological; Risk Assessment; Safety and security measures; Time Factors; Torsades de Pointes - chemically induced; Torsades de Pointes - physiopathology; Veins & arteries; United States > US; Japan; QT interval; Atrial fibrillation; Effective refractory period; Early repolarization; Amiodarone; Bepridil; Torsade de pointes; Sotalol; dl-Sotalol
• ISSN: 1530-7905; 1559-0259
• DOI: 10.1007/s12012-016-9369-8

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 – T peak or the late repolarization done by T peak – T end in 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.