This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nanas, J. N. Articles by Mason, J. W. Search for Related Content PubMed PubMed Citation Articles by Nanas, J. N. Articles by Mason, J. W.

(Circulation. 1995;91:451-461.)
© 1995 American Heart Association, Inc.

Articles

Pharmacokinetics and Regional Electrophysiological Effects of Intracoronary Amiodarone Administration

John N. Nanas, MD, PhD; Jay W. Mason, MD, FACC

From the University of Athens (Greece) School of Medicine, Department of Clinical Therapeutics, and the University of Utah Health Sciences Center, Division of Cardiology, Salt Lake City.

Correspondence to Jay W. Mason, MD, FACC, University of Utah Health Sciences Center, Division of Cardiology, 50 North Medical Dr, Salt Lake City, UT 84132.

Background The reason for the delay in onset of the electrophysiological effects and antiarrhythmic efficacy of amiodarone is not clear. The relation between the development of the electrophysiological effects of amiodarone and its myocardial concentration is unknown. We therefore examined the time course of development of electrophysiological effects during intracoronary infusion of amiodarone and related these changes to myocardial concentrations.

Methods and Results Amiodarone (0.139 mg/min) or normal saline was infused for 10 hours into the proximal left anterior descending coronary artery of 24 open-chest dogs. Nineteen animals received intracoronary amiodarone and 5 received normal saline (control group). Ten of the 19 that received amiodarone underwent electrophysiological study (amio-EPS group). Sixteen of the 19, including 7 from the amio-EPS group, underwent pharmacological study (PS group). In the amio-EPS group during pacing at a cycle length of 300 ms, changes in conduction velocities in drug-exposed myocardium referenced to nonexposed myocardium at 1 hour of infusion were -3.7% in the longitudinal direction (P=NS) and -7.2% in the transverse direction (P<.05); at 3 hours, -12.9% (P<.05) and -9.1% (P<.05); and at 9 hours, -32.9% (P<.02) and -31.7% (P<.01). These changes were dependent on amiodarone concentration (R²=.83). There was also an obvious rate-dependent effect that was more pronounced for transverse conduction velocities. This effect was also dependent on amiodarone concentration. In the PS group, amiodarone levels in the drug-exposed myocardium increased from a mean of 5.95 µg/g at 15 minutes of infusion to 188.88 µg/g at the 10th hour. This increase was time dependent (R²=.91). In the nonexposed myocardium, amiodarone levels were always low and increased minimally over time from a mean of 2.68 to 14.45 µg/g. This increase was also time dependent (R²=.97).

Conclusions Selective intracoronary amiodarone infusion resulted in selective drug accumulation and concomitant time-dependent reduction of myocardial conduction velocity. There was a significant correlation between the extent of reduction of conduction velocity and myocardial amiodarone concentration but not coronary arterial or systemic concentration. Repolarization was not significantly altered.

Key Words: amiodarone • pharmacokinetics • conduction

This article has been cited by other articles:

				P. Kirchhof, H. Degen, M. R. Franz, L. Eckardt, L. Fabritz, P. Milberg, S. Laer, J. Neumann, G. Breithardt, and W. Haverkamp Amiodarone-Induced Postrepolarization Refractoriness Suppresses Induction of Ventricular Fibrillation J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 257 - 263. [Abstract] [Full Text]

				I. Kodama, K. Kamiya, and J. Toyama Cellular electropharmacology of amiodarone Cardiovasc Res, July 1, 1997; 35(1): 13 - 29. [Full Text] [PDF]