A Comparison of the Electrophysiologic Effects of Acute and Chronic Amiodarone Administration on Canine Purkinje Fibers

Abstract

The electrophysiologic effects of acutely and chronically administered amiodarone on canine Purkinje fibers were assessed using microelectrode techniques to record intracellular action potentials. Chronically treated dogs received amiodarone for 3 weeks (serum levels, 0.91 +/- 0.09 microgram/ml or 1.42 X 10(-6) M). Acute studies were performed using fibers from untreated dogs superfused for 1 h with 5 X 10(-5) M amiodarone (32 micrograms/ml) in Tyrode's solution (KCl = 4 mM). Acute superfusion shortened the action potential duration to 50 and 90% repolarization by 41 and 8%, respectively (p less than 0.01), and decreased Vmax of phase 0 from 418 +/- 20 to 309 +/- 23 V/s (p less than 0.01) (paced cycle length of 500 ms). Prominent use-dependent depression of Vmax was noted. Acute exposure of fibers from untreated dogs to blood from dogs chronically treated with amiodarone using the blood cross-perfusion technique decreased the action potential duration to 50% repolarization and Vmax, similar to acute exposure in Tyrode's solution. Blood cross-perfusion was used to study fibers from treated dogs superfused with blood from another amiodarone-treated dog. Chronic amiodarone prolonged the action potential duration to 90% repolarization by 13% (p less than 0.02) and did not change Vmax when compared to control studies using fibers obtained from untreated dogs superfused with blood from untreated dogs. Thus, the effects of acutely superfused amiodarone on action potentials of canine Purkinje fibers differ from the effects of chronically administered amiodarone.