Rate-related electrophysiologic effects of long-term administration of amiodarone on canine ventricular myocardium in vivo.

Abstract

The electrophysiologic effects of amiodarone were examined in 13 dogs that received 30 g amiodarone orally during 3 weeks and compared with 13 control dogs that did not receive amiodarone. Longitudinal and transverse epicardial conduction velocities were estimated with a square array of 64 closely spaced electrodes and a computer-assisted acquisition and analysis system. Amiodarone caused a rate-dependent decrease in conduction velocity with a slightly greater effect in the longitudinal direction of propagation. Rate-related depression of conduction velocity developed rapidly after abrupt shortening of the pacing cycle length; 67% of the change occurred between the first two beats of the rapid train, and little change occurred after the 10th beat. Recovery from use-dependent depression of conduction velocity was exponential with a mean time constant of 447 +/- 172 msec in the longitudinal direction and 452 +/- 265 msec in the transverse direction. Repolarization intervals, defined as the interval between the activation time and the repolarization time in the unipolar electrograms, correlated highly with refractory period determinations in the absence and presence of amiodarone at each cycle length tested. The increase in repolarization intervals and refractory periods resulting from amiodarone treatment did not vary with cycle length. Amiodarone treatment also resulted in a significant rate-related reduction in systolic blood pressure. The systolic blood pressure in the group that received amiodarone decreased by a mean of 50 +/- 23% between steady-state pacing cycle lengths of 1,000 and 200 msec, whereas the corresponding decrease in the control group was 21 +/- 32% (p less than 0.05). Plasma and myocardial amiodarone and desethylamiodarone levels were comparable to those observed clinically. We conclude that long-term amiodarone administration causes rate-dependent reductions in conduction velocity and blood pressure and causes rate-independent increases in repolarization intervals.