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(Circulation. 1999;100:1836-1842.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Digoxin Delays Recovery From Tachycardia-Induced Electrical Remodeling of the Atria

Robert G. Tieleman, MD; Yuri Blaauw, MD; Isabelle C. Van Gelder, MD, PhD; Cees D. J. De Langen, PhD; Pieter J. de Kam, MSc; Jan G. Grandjean, MD, PhD; Kornelis W. Patberg, MD; Klaas J. Bel, BSc; Maurits A. Allessie, MD, PhD; Harry J. G. M. Crijns, MD, PhD

From the Department of Cardiology, Thoraxcenter, and Department of Clinical Pharmacology, University of Groningen; and the Department of Physiology, University of Limburg, Netherlands.

Correspondence to R.G. Tieleman, MD, Department of Cardiology, Thoraxcenter, University Hospital Groningen, PO Box 30001, 9700 RB Groningen, Netherlands.

Background—Atrial fibrillation (AF) induces electrical remodeling, which is thought to be responsible for the low success rate of antiarrhythmic treatment in AF of longer duration. Electrical remodeling seems to be related to tachycardia-induced intracellular calcium overload. Due to its vagomimetic action, digoxin is widely used to control the ventricular rate during AF, but it also increases intracellular calcium. On the basis of these characteristics, we hypothesized that digoxin would aggravate tachycardia-induced electrical remodeling.

Methods and Results—We analyzed the atrial effective refractory period (AERP) at cycle lengths of 430, 300, and 200 ms during 24 hours of rapid atrio/ventricular (300/150 bpm) pacing in 7 chronically instrumented conscious goats treated with digoxin or saline. Digoxin decreased the spontaneous heart rate but had no other effects on baseline electrophysiological characteristics. In addition to a moderate increase in the rate of electrical remodeling during rapid pacing, digoxin significantly delayed the recovery from electrical remodeling after cessation of pacing (at 430, 300, and 200 ms: P=0.001, P=0.0015, and P=0.007, respectively). This was paralleled by an increased inducibility and duration of AF during digoxin. Multivariate analysis revealed that both a short AERP and treatment with digoxin were independent predictors of inducibility (P=0.001 and P=0.03, respectively) and duration (P=0.001 for both) of AF.

Conclusions—Digoxin aggravates tachycardia-induced atrial electrical remodeling and delays recovery from electrical remodeling in the goat, which increases the inducibility and duration of AF.

Key Words: fibrillation • pacing • remodeling • digoxin • calcium • nervous system, autonomic

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