D,l-sotalol reverses abbreviated atrial refractoriness and prevents promotion of atrial fibrillation in a canine model with left ventricular dysfunction induced by atrial tachypacing

Abstract

Background: This study evaluated antiarrhythmic effects of d,l-sotalol in a canine atrial fibrillation (AF) model with left ventricular dysfunction. Methods and Results: Thirteen beagles (Sotalol group n=7 and Control group n=6) were subjected to atrial tachypacing (ATP) (400 beats/min) with intact atrioventricular conduction for 4 weeks. Oral d,l-sotalol (2 mg/kg) was administered 1 week after starting ATP and continued throughout the experiment. One week after starting ATP, atrial effective refractory periods (AERPs) were shortened in both groups. However, d,l-sotalol treatment gradually prolonged AERP, resulting in a significant prolongation of AERP compared with the Control group at 4 weeks (Control 76±4 and Sotalol 126±5 ms, P<0.01). d,l-Sotalol treatment showed lower AF inducibility and shorter AF duration at 4 weeks. In the control group, expressions of L-type Ca2+ channel α1c and Kv4.3 mRNA were downregulated by 46.2% and 43.0%, respectively, after 4 weeks of ATP; d,l-sotalol treatment did not affect these changes. Conclusions: d,l-Sotalol treatment prolonged AERP, even after atrial electrical remodeling had developed, and prevented AF perpetuation without affecting downregulated expression of L-type Ca2+ channel α1c and Kv4.3 mRNA in an ATP-induced canine AF model.