title: Mechanisms of depressed conduction from long-term amiodarone therapy in canine myocardium.
abstract: Amiodarone therapy leads to a significant impairment in myocardial conduction, yet it causes only a modest decrease in the maximum rate of depolarization of the action potential (dV/dT). To determine whether the decrease in dV/dT solely accounts for the impaired myocardial conduction or whether passive membrane properties may also be involved, we studied 21 ventricular epicardial tissues from 14 beagles; six dogs received long-term treatment (3-6 weeks) of amiodarone orally, and the remaining dogs served as controls. Amiodarone therapy was associated with a decrease in conduction velocity (0.41 +/- 0.15 vs. 0.56 +/- 0.05 m/sec; p less than 0.01). There was a trend toward a decrease in dV/dT and a significant decrease in the space constant (0.69 +/- 0.27 vs. 1.05 +/- 0.25 mm; p = 0.01), of which the latter correlated closely with the decrease in conduction velocity measured in the amiodarone-treated tissues (r = 0.85, p less than 0.05). These data indicate that the decrease in myocardial conduction velocity caused by amiodarone is primarily due to effects on overall resistance to passive current flow rather than effects on the inward sodium current.
authors.affiliation: Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: J H
authors.initials: JH
authors.lastname: Levine
authors.forename: E N
authors.initials: EN
authors.lastname: Moore
authors.forename: A H
authors.initials: AH
authors.lastname: Kadish
authors.forename: H F
authors.initials: HF
authors.lastname: Weisman
authors.forename: C W
authors.initials: CW
authors.lastname: Balke
authors.forename: R F
authors.initials: RF
authors.lastname: Hanich
authors.forename: J F
authors.initials: JF
authors.lastname: Spear
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000009:adverse effects*; D000818:Animals; D001696:Biomechanical Phenomena; D004285:Dogs; D006321:Heart / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects*; D008955:Models, Cardiovascular; D013997:Time Factors
chemical_list: D000638:Amiodarone