title: Renal denervation regulates the atrial arrhythmogenic substrates through reverse structural remodeling in heart failure rabbit model.
abstract: BACKGROUND
  Heart failure (HF) causes atrial remodeling and increases the incidence of atrial fibrillation (AF). Renal denervation (RDN) has been shown to decrease the development of AF. This study aimed to identify the effects of RDN on the atrial arrhythmogenic substrates in HF.
  
  
  METHODS
  Rabbits were classified into four groups: control (n=9), RDN (n=10), HF (n=6) and HF-RDN (n=9). Surgical and chemical RDN was approached through bilateral retroperitoneal flank incisions in RDN and HF-RDN. Rapid ventricular pacing of 400bpm for 4weeks was applied in HF and HF-RDN. After 4weeks, the rabbits were sacrificed and atrial myocardium were harvested for Western blot and Trichrome stain.
  
  
  RESULTS
  The bi-atrial effective refractory period (ERP) of HF was significantly longer compared with that of control and RDN. In right atrium, the ERP of HF was also significantly longer compared with that of HF-RDN, but there was no significant difference in left atrial ERP. In bi-atrium, ion channel protein expressions of CaV1.2, NaV1.5, Kir2.1 SERCA2 and NCX were similar among 4 groups. However, the degree of atrial fibrosis was extensive in bi-atrium of HF, when compared to that of control, RDN and HF-RDN.
  
  
  CONCLUSIONS
  The ERP of HF-RDN is partially shortened by RDN compared with that of HF. There are no differences ionic channel protein expressions in bi-atrium among all groups. The degree of atrial fibrosis is severe in HF, but not in HF-RDN, suggesting that RDN may regulate the atrial arrhythmogenic substrates in HF mostly through reverse structural remodeling.
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Cardiovascular Medicine, Fukushima Medical University, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Lo
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Chou
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shih-Lin
authors.initials: SL
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yenn-Jiang
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan. Electronic address: epsachen@ms41.hinet.net.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D064752:Atrial Remodeling; D004195:Disease Models, Animal; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology; D006333:Heart Failure / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D007473:Ion Channels / Q000032:analysis; D007668:Kidney / Q000294:innervation; D011817:Rabbits; D013562:Sympathectomy / Q000379:methods*; D017779:Sympathetic Fibers, Postganglionic / Q000601:surgery
chemical_list: D007473:Ion Channels
keywords: Atrial arrhythmogenic substrates; Atrial structural remodeling; Renal denervation; Sympathetic nervous system