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

Abstract

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-α 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.

Catheter-Based Renal Denervation Reduces Atrial Nerve Sprouting and Complexity of Atrial Fibrillation in Goats

“…18 The effect of RDN on the development of an atrial structural remodeling and AF has not been investigated sufficiently. 19 In particular, the influence of RDN on the complexity of AF propagation patterns, 20 representing the functional consequence of atrial structural remodeling, 21,22 has not yet been studied. This study is aimed to determine the effect of sympathetic nervous system modulation by RDN on structural and neural remodeling in the atrium and AF complexity in a goat model of persistent AF without hypertension or structural heart disease.…”

Beneficial Effect of Renal Denervation on Ventricular Premature Complex Induced Cardiomyopathy

“…Therefore, RDN may be an effective therapy for management of ventricular arrhythmia because RDN can regulate renin‐angiotensin‐aldosterone system activation and sympathetic activity 14, 15. Our study demonstrated that VF inducibility was higher in VPC rabbits than that in control rabbits.…”

The impact of renal sympathetic denervation on cardiac electrophysiology and arrhythmias: A systematic review of the literature

“…The impact of RDN on atrial remodeling and AF inducibility caused by right atrial pacing has also been studied in a dog model [25]. During programmed stimulation chronic right atrial pacing group dogs exhibited higher numbers of AF inducements compared to sham group.…”

“…During programmed stimulation chronic right atrial pacing group dogs exhibited higher numbers of AF inducements compared to sham group. Moreover, it was indicated that RDN could suppress atrial remodeling induced by right atrial pacing [25]. On the other hand, in a pig model investigators showed that increased AF inducibility after atrial tachypacing was not changed by RDN while AF cycle length after 30 minutes of atrial tachypacing 10 was decreased compared with baseline and not further modulated by RDN [26].…”