title: 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.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan City, People's Republic-PR. of China.
authors.forename: Xule
authors.initials: X
authors.lastname: Wang
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Zhao
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Tang
authors.forename: Jinping
authors.initials: J
authors.lastname: Xiao
authors.forename: Zixuan
authors.initials: Z
authors.lastname: Dai
authors.forename: Shengbo
authors.initials: S
authors.lastname: Yu
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
mesh_terms: D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001281:Atrial Fibrillation / Q000503:physiopathology / Q000628:therapy; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D064752:Atrial Remodeling; D001794:Blood Pressure; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D005355:Fibrosis; D019922:GAP-43 Protein / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism / Q000473:pathology; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000294:innervation* / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D013562:Sympathectomy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019922:GAP-43 Protein; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D000450:Aldosterone; D009320:Atrial Natriuretic Factor