Effect of renal sympathetic denervation on atrial substrate remodeling in ambulatory canines with prolonged atrial pacing

• Published in: PloS one Vol. 8; no. 5; p. e64611
• Main Authors: Wang, Xule, Zhao, Qingyan, Huang, He, Tang, Yanhong, Xiao, Jinping, Dai, Zixuan, Yu, Shengbo, Huang, Congxin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.05.2013; Public Library of Science (PLoS)
• Subjects: Aldosterone; Aldosterone - blood; Angiotensin; Angiotensin II; Angiotensin II - blood; Animals; Apoptosis; Atrial Fibrillation - physiopathology; Atrial Fibrillation - therapy; Atrial Natriuretic Factor - metabolism; Atrial Remodeling; Audio frequencies; Bax protein; Bcl-2 protein; Blood Pressure; Cardiac arrhythmia; Cardiac Pacing, Artificial; Cardiology; Caspase; Caspase-3; Catheters; Cystic fibrosis; Denervation; Dogs; Enzymes; Fibrillation; Fibrosis; Gap Junctions - metabolism; Gap Junctions - pathology; GAP-43 Protein - metabolism; Gene expression; Heart; Heart Atria - metabolism; Heart Atria - pathology; Heart diseases; Hospitals; Hypertension; Immunohistochemistry; Inflammation; Inflammation - metabolism; Inhibition; Interleukin 6; Interleukin-6 - metabolism; Kidney - innervation; Kidney - surgery; Kidneys; Laboratory animals; Medical instruments; Medicine; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Nerves; Picric acid; Plasma levels; Remodeling; Rodents; Studies; Substrates; Sympathectomy; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Veins & arteries; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0064611

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.