Losartan affects the substrate for atrial fibrillation maintenance in a rabbit model

Abstract

Background: Atrial fibrosis causes abnormal conduction through the atria, creating a substrate for atrial fibrillation (AF). In a rabbit model, rapid atrial pacing produces significant atrial fibrosis and the substrate for AF maintenance. This atrial remodeling is a potential therapeutic target.

Objective: To evaluate the effects of the losartan on atrial fibrosis.

Methods: Thirty rabbit AF models were produced by rapid atrial stimulation. They were randomly divided into three groups: sham group, rapid atrial pacing group, and rapid atrial pacing with losartan group. We performed AF vulnerability studies, atrial histologic, and molecular analyses after 4 weeks.

Results: Only rabbits in the rapid atrial pacing group developed sustained AF (30 min, 4of 10 rabbits). Treatment with losartan resulted in a significant reduction in left atrial fibrosis and AF duration (P<.01). real-time polymerase chain reaction analyses demonstrated the drug's effects on the expression of Collagen I, Collagen III, and TGF-β/Smads signaling pathway.

Conclusions: The treatment of losartan results in significantly reduced atrial fibrosis and AF vulnerability. Pharmacological therapy targeted at the fibrotic substrate itself may play an important role in the management of AF.

Keywords: Atrial fibrillation; Atrial fibrosis; Losartan; Substrate.