Effects of doxycycline on atrial electrical remodeling in a rat model of atrial fibrillation

Abstract

Purpose Previous studies showed that doxycycline (Dox), a matrix metalloproteinase inhibitor, can attenuate chronic intermittent hypoxia (CIH)-induced atrial fibrosis in our rats. On this basis, we further investigated the effects of Dox on CIH-induced atrial electrical remodeling in rats. Methods Rats were randomized into 3 groups: Control group, CIH group, and CIH with Dox treatment (CIH-D) group (n = 30). CIH and CIH-D rats were subjected to CIH 8 h/d for 6 weeks. After collecting the basic parameters of the rats, atrial fibrillation (AF) inducibility, conduction inhomogeneity, and epicardial conduction velocity were examined by vitro cardiac electrophysiology experiments. The expression levels of ion channel subunits in atrium were detected by Western blotting. Whole-cell patch clamp experiments were used to recorded action potential (AP), INa, ICa−L, Ito, and the kinetic parameters. Results Compared to the Control rats, CIH rats showed increased AF inducibility, conduction inhomogeneity, and expression levels of p-RyR2, p-CaMKII, Kv11.1, Kir2.3, KCa3.1, while the epicardial conduction velocity, ICa−L, Ito, and expression levels of Cav1.2, Kv1.5, Kv4.3 were decreased. Dox-treatment significantly improved the expression levels of Kv1.5, Kv4.3 and Kir2.3 in CIH-D rats. Conclusion CIH caused atrial electrical remodeling in our rats, which was improved by Dox treatment. These changes indicated the potential effects of Dox in AF.