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.
Highlights
Studies have indicated that the renin-angiotensin-aldosterone system (RAAS) has been shown to an important hormonal system in the initiation and pathogenesis of atrial fibrillation (AF) [1,2,3]
Sham-operated group consisted of 6 dogs that were implanted with pacemakers without pacing; chronic RAP (CRAP) group consisted of 7 dogs that were implanted with pacemakers with right atrial pacing (RAP) for 5 weeks; and CRAP+renal sympathetic denervation (RSD) group consisted of 7 dogs that first underwent catheter-based RSD and were implanted with pacemakers after they recovered from RSD
Results showed that RSD could suppress the AF vulnerability, the renin-angiotensin-aldosterone systematic activity and atrial remodeling, including the significantly increased atrial fibrosis, inflammation and apoptosis, together with atrial gap junctional remodeling and neural remodeling that are produced by long-term RAP in ambulatory canines
Summary
Studies have indicated that the renin-angiotensin-aldosterone system (RAAS) has been shown to an important hormonal system in the initiation and pathogenesis of atrial fibrillation (AF) [1,2,3]. Inhibitors of the RAAS, such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers, are emerged as novel drugs for the prevention and treatment of AF [4,5,6]. These drugs may not possess direct anti-arrhythmic properties, a large number of research on AF have shown that RAAS blockade has beneficial effects on cardiac remodeling, which is specally related to RAAS inhibition [7,8,9,10]. Inhibition of the renin-angiotensin system decreases cardiomyocyte fibrosis, apoptosis and inflammation [16,17,18,19]
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