Acute effects of amiodarone on membrane properties, refractoriness, and conduction in guinea pig papillary muscles

Amiodarone has potent and complex antiarrhythmic effects associated with a rare incidence of proarrhythmia. For a comprehensive understanding of its antiarrhythmic mechanisms in the same preparations, amiodarone (50 μM) was employed as it would be in the clinical setting and applied to guinea pig papillary muscles impaled by microelectrodes, paced at different rates, and superfused with various concentrations of potassium ([K]_e). Amiodarone exerted complex actions, as follows: (1) The maximum rate of rise (V_max) of the fast action potential (i.e., [K]_e = 5.4-9.0mM) as well as that of the slow action potential (i.e., [K]_e = 15.0mM in the presence of 1.0μM isoproterenol) was suppressed in a rate-dependent manner. (2) Amiodarone exhibited a rate- and [K]_e-dependent increase in the ratio of effective refractory period vs action potential duration at 90% repolarization (ERP/APD₉₀), disclosing post-repolarization refractoriness. (3) Amiodarone had no effect on passive cable factors, such as threshold current and tissue resistance, during propagation. These versatile electrophysiological effects of amiodarone may contribute to its unique antiarrhythmic effects, as well as the low incidence of proarrhythmia with this drug.