Chronic in vivo and in vitro effects of amiodarone on guinea pig hearts.
- Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York, USA.
Abstract
To study the electrophysiologic effects of chronically administered amiodarone and its interaction with an I(Kr) blocker, amiodarone was injected i.p. daily for 7 days into male guinea pigs. Control animals received vehicle only. At 80 mg/kg, RR and rate corrected QT (QT(C)) intervals increased after 4 days from 209 +/- 5 ms and 162 +/- 3 respectively to 285 +/- 13 ms and 176 +/- 3 (P < .05, n = 10), respectively, and remained significantly high on the 8th day (256 +/- 14 ms and 173 +/- 4). Neither RR nor QT(C) intervals changed significantly in control animals. Twenty-four hours after the last injection, papillary muscles were isolated from both ventricles and superfused with Tyrode's solution not containing amiodarone. The preparations from amiodarone-treated animals manifested a statistically significant prolongation of action potential duration (APD) at all pacing cycle lengths (CL) (from 300 to 1500 ms). The amiodarone-induced increase of APD diminished with elevation of potassium concentration ([K+]O). Amiodarone did not modify the dependence of Vmax on membrane potential at different [K+]O. There was minimal to no summation of effects of chronic amiodarone and acute super-fusion of the I(Kr) blocker, E-4031 (3 x 10(-6) M) on APD at CL = 1500 ms. The data demonstrate that in chronically treated guinea pigs, amiodarone prolongs repolarization, manifests minimum reverse use-dependent in APD prolongation, and, at low pacing rate, shows no additive actions with an acutely superfused blocker of I(Kr).
