Effect of Renal Sympathetic Denervation on Atrial Substrate Remodeling in Ambulatory Canines with Prolonged Atrial Pacing

We have previously demonstrated that catheter-based renal sympathetic denervation (RSD) could suppress atrial fibrillation (AF) in canines with short-time rapid right atrial pacing (RAP). However, the role of renal denervation on atrial remodeling is unclear. The aim of the present study was to explore the long-term effect of RSD on the atrial remodeling during prolonged RAP. Twenty mongrel dogs were implanted with a high-frequency cardiac pacemaker with a transvenous lead inserted into the right atrial appendage. The dogs were divided into three groups: a sham-operated group (n = 6), the chronic RAP (CRAP) group (n = 7), and the CRAP+RSD group (n = 7). In the CRAP+RSD group, a pacemaker was implanted 6 weeks after RSD was performed bilaterally for recovery. RAP was maintained for 5 weeks in CRAP group and CRAP+RSD group. The plasma levels of Angiotensin II and aldosterone were significantly increased in CRAP group compared with sham-operated group, but the increasing trend was inhibited in CRAP+RSD group compared with CRAP group (P<0.05). Similarly, RSD suppressed the increasing trend that prolonged RAP produced in the left atrial levels of ANP, TNF-alpha and IL-6. Compared with the sham-operated group, the CRAP group had significantly increased levels of caspase-3, bax and Cx40 whereas the level of Bcl-2 decreased (P<0.05). RSD markedly reduced the upregulation of caspase-3, bax and Cx40 and the downregulation of Bcl-2 expression compared with the CRAP group (P<0.05). Picric acid-sirius red staining study suggested that RSD could markedly alleviate the lesion degree of cardic fibrosis induced by CRAP (P<0.05). Immunohistochemistry results showed that the densities of TH- and GAP43-positive nerves were significantly elevated in the CRAP group compared with the sham-operated group, while RSD operation signicantly inhibited the these changes produced by CRAP. These findings suggest that renal denervation could suppress the atrial remodeling after prolonged RAP in ambulatory canines.