Electrophysiological response to acehytisine was modulated by aldosterone in rats with aorto-venocaval shunts

Abstract

Aldosterone induces cardiac electrical and structural remodeling, which leads to the development of heart failure and/or atrial fibrillation (AF). However, it remains unknown whether aldosterone-induced remodeling may modulate the efficacy of anti-AF drugs. In this study, we aimed to jeopardize the structural and functional remodeling by aldosterone in rats with aorto-venocaval shunts (AVS rats) and evaluate the effect of acehytisine in this model. An AVS operation was performed on rats (n=6, male) and it was accompanied by the intraperitoneal infusion of aldosterone (AVS+Ald) at 2.0 μg/hr for 28 days. The cardiopathy was characterized by echocardiography, electrophysiologic and hemodynamic testing, and morphometric examination in comparison with sham-operated rats (n=3), sham+Ald (n=6), and AVS (n=5). Aldosterone accelerated the progression from asymptomatic heart failure to overt heart failure and induced sustained AF resistant to electrical fibrillation in one out of six rats. In addition, it prolonged PR, QT interval and Wenckebach cycle length. Acehytisine failed to suppress AF in the AVS+Ald rats. In conclusion, aldosterone jeopardized electrical remodeling and blunted the electrophysiological response to acehytisine on AF.