Digoxin delays recovery from tachycardia-induced electrical remodeling of the atria

Background-Atrial fibrillation (AF) induces electrical remodeling, which is thought to be responsible for the low success rate of antiarrhythmic treat ment 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 characte ristics, we hypothesized that digoxin would aggravate tachycardia-induced e lectrical remodeling. Methods and Results-We analyzed the atrial effective refractory period (AER P) 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 go ats treated with digoxin or saline. Digoxin decreased the spontaneous heart rate but had no other effects on baseline electrophysiological characteris tics. In addition to a moderate increase in the rate of electrical remodeli ng during rapid pacing, digoxin significantly delayed the recovery from ele ctrical 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 increa sed inducibility and duration of AF during digoxin. Multivariate analysis r evealed 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 remode ling and delays recovery from electrical remodeling in the goat, which incr eases the inducibility and duration of AF.