title: Renal failure induces atrial arrhythmogenesis from discrepant electrophysiological remodeling and calcium regulation in pulmonary veins, sinoatrial node, and atria.
abstract: BACKGROUND
  Renal failure (RF) increases the risk of atrial fibrillation (AF), but arrhythmogenic mechanism is unclear. The present study investigated the electrophysiological effects of RF on AF trigger (pulmonary veins, PVs) and substrate (atria) and evaluated potential underlying mechanisms.
  
  
  METHODS
  Electrocardiographic, echocardiographic, and biochemical studies were conducted in rabbits with and without antibiotic-induced mild (creatinine=1.5-6.0 mg/dl) and advanced (creatinine>6.0 mg/dl) RF. Conventional microelectrode techniques, western blotting, and histological examinations were performed using the isolated rabbit PV, left atrium (LA), right atrium (RA) and sinoatrial node (SAN).
  
  
  RESULTS
  Advanced RF rabbits (n=18) had a higher incidence (33.3% vs. 11.1% and 0%, p<0.05) of atrial arrhythmia than mild RF (n=18) and control (n=18) rabbits. Advanced RF rabbits exhibited faster PV spontaneous activities, longer action potential duration (APD) in the LA, higher fibrosis in the LA, and slower SAN beating rates than control rabbits, but had a similar APD and fibrosis in the RA. Caffeine (1 mM) increased advanced RF PV arrhythmogenesis, which is blocked by flecainide (10 μM), or KB-R7943 (10 μM). Moreover, advanced RF rabbits had a higher expression of the Na+/Ca2+ exchanger, protein kinase A, phosphorylated ryanodine receptor (Serine 2808), and phosphorylated phospholamban (Serine 16) in PVs, and a higher expression of Cav 1.2 in the LA, and a lower expression of hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 in the SAN.
  
  
  CONCLUSIONS
  Advanced RF increases atrial arrhythmia by modulating the distinctive electrophysiological characteristics of the PV, LA, and SAN.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Shih-Yu
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Kao
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Hsiung
authors.initials: MH
authors.lastname: Hsieh
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City, Taiwan.
authors.forename: Yi-Ann
authors.initials: YA
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Sijhih Cathay General Hospital, New Taipei City, Taiwan.
authors.forename: Wan-Ping
authors.initials: WP
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
authors.affiliation: School of Medicine, National Yang-Ming University, Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: a9900112@ms15.hinet.net.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D064752:Atrial Remodeling / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D004562:Electrocardiography / Q000379:methods; D006325:Heart Atria / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D011667:Pulmonary Veins / Q000378:metabolism / Q000503:physiopathology*; D011817:Rabbits; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D012849:Sinoatrial Node / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D002118:Calcium
keywords: Atrial fibrillation; Chronic kidney disease; Left atrium; Pulmonary vein; Sinoatrial node