title: Atrial tachycardia provoked in the presence of activating autoantibodies to β2-adrenergic receptor in the rabbit.
abstract: BACKGROUND
  A recent clinical study of patients with inappropriate sinus tachycardia reported that autoantibodies to β-adrenergic receptors (β2ARs) could act as agonists to induce atrial arrhythmias.
  
  
  OBJECTIVE
  To test the hypothesis that activating autoantibodies to the β2AR in the rabbit atrium are arrhythmogenic.
  
  
  METHODS
  Five New Zealand white rabbits were immunized with a β2AR second extracellular loop peptide to raise β2AR antibody titers. A catheter-based electrophysiologic study was performed on anesthetized rabbits before and after immunization. Arrhythmia occurrence was determined in response to burst pacing before and after the infusion of acetylcholine in incremental concentrations of 10 μM, 100 μM, and 1 mM at 1 mL/min.
  
  
  RESULTS
  In the preimmune studies when β2AR antibody titers were undetectable, of a total of 20 events, only 3 episodes of nonsustained (<10 seconds) atrial arrhythmias were induced. In the postimmune studies when β2AR antibody titers ranged from 1:160,000 to 1:1.28 million, burst pacing induced 10 episodes of nonsustained or sustained (≥10 seconds) arrhythmias in 20 events (P = .04 vs preimmune; χ(2) and Fisher exact test). Taking into account only the sustained arrhythmias, there were 6 episodes in 20 events in the postimmune studies compared with 0 episodes in 20 events in the preimmune studies (P = .02). Immunized rabbits demonstrated immunoglobulin G deposition in the atria, and their sera induced significant activation of β2AR in transfected cells in vitro compared to the preimmune sera.
  
  
  CONCLUSIONS
  Enhanced autoantibody activation of β2AR in the rabbit atrium leads to atrial arrhythmias mainly in the form of sustained atrial tachycardia.
authors.affiliation: Heart Rhythm Institute and Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Scherlag
authors.forename: David C
authors.initials: DC
authors.lastname: Kem
authors.forename: Caitlin
authors.initials: C
authors.lastname: Zillner
authors.forename: Shailesh
authors.initials: S
authors.lastname: Male
authors.forename: Sorkko
authors.initials: S
authors.lastname: Thirunavukkarasu
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Shen
authors.forename: Jan V
authors.initials: JV
authors.lastname: Pitha
authors.forename: Madeleine W
authors.initials: MW
authors.lastname: Cunningham
authors.forename: Ralph
authors.initials: R
authors.lastname: Lazzara
authors.forename: Xichun
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D001323:Autoantibodies / Q000276:immunology*; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D004797:Enzyme-Linked Immunosorbent Assay; D006325:Heart Atria / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D011817:Rabbits; D018343:Receptors, Adrenergic, beta-2 / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D018343:Receptors, Adrenergic, beta-2