Atsushi Sugiyama*, Yoshioki Satoh and Keitaro Hashimoto
Department of Pharmacology, Yamanashi Medical University, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan
*Corresponding author. FAX: +81-55-273-6739, E-mail: atsushis@res.yamanashi-med.ac.jp
Abstract: Acute hemodynamic and electrophysiological effects of amiodarone were assessed simultaneously, using the halothane-anesthetized, closed-chest in vivo canine model in comparison with those of solvent ethanol alone. Intravenous administration of the solvent (n = 8) induced no significant change in any of the cardiovascular parameters. On the other hand, intravenous amiodarone in the canine antiarrhythmic dose of 3.0 mg/kg (n = 6) exerted negative chronotropic, inotropic and dromotropic effects in addition to the transient hypotensive action followed by an increase of the total peripheral vascular resistance. Amiodarone also prolonged both the ventricular repolarization phase and the effective refractory period, where the increment was greater in the latter than in the former, indicating the shortening of the electrical vulnerable period of the ventricle. More importantly, appearance of the electrophysiological effect on repolarization took more time and higher dose compared with the effect on refractoriness, which could be detected at a one tenth the dose. These results support the previous knowledge that intravenously administered amiodarone possesses class I, III and IV actions and suggest that shortening of the electrical vulnerable period may be one of the unique antiarrhythmic properties of intravenous amiodarone against re-entry type arrhythmias.
Keywords: Amiodarone, Monophasic action potential, IKs, IKr, Repolarization
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