Effects of renal sympathetic denervation on the development of atrial fibrillation substrates in dogs with pacing-induced heart failure

Abstract

The present study examined the effect of catheter-based renal sympathetic denervation (RSD) on atrial fibrillation (AF) vulnerability and atrial substrate remodeling in a canine high-rate ventricular pacing model. Animal handling was performed in accordance with theWuhan Directive for Animal Research and the current Guidelines for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH publication no. 85-23, revised 1996). The ethics committee at Wuhan University approved the study protocol. Nineteen adult mongrel dogs were divided into three groups. The pacemakers in the sham-operated group were implanted in a subcutaneous pocket and attached to a pacing lead (Medtronic, Inc., Capture Sense, 4574, USA) in the right ventricular apex. All of the animals recovered for 3 weeks without pacing. The pacemakers were implanted in the heart failure (HF) group, and the dogs underwent ventricular rapid pacing at 240 beats per minute (bpm) for 3 weeks. The dogs in the HF+ RSD group underwent renal artery ablation (RAA) prior to ventricular rapid pacing [1]. After 8 weeks, pacemakers were implanted, and the dogs underwent ventricular rapid pacing for 3 weeks. The femoral artery blood pressure, electrophysiological measurements, echocardiography, left ventricular end-systolic pressure (LVESP), and left ventricular end-diastolic pressure (LVEDP) were measured in all of the animals at baseline and after 3 weeks of pacing. The BNP, Ang II and TNF-α levels were measured in the atrial tissue samples using ELISA and TGF-β was measured using the Western blot. Masson's trichrome staining was used to identify increased concentration of interstitial fibrosis.