title: A peptidomimetic inhibitor suppresses the inducibility of β1-adrenergic autoantibody-mediated cardiac arrhythmias in the rabbit.
abstract: OBJECTIVE
  Previous studies demonstrated that burst pacing and subthreshold infusion of acetylcholine in β1-adrenergic receptor (β1AR)-immunized rabbits induced sustained sinus tachycardia. The aim of this study was to examine the anti-arrhythmogenic effect of a newly designed retro-inverso (RI) peptidomimetic inhibitor that specifically targets the β1AR antibodies in the rabbit.
  
  
  METHODS
  Six New Zealand white rabbits were immunized with a β1AR second extracellular loop peptide to produce sympathomimetic β1AR antibodies. A catheter-based electrophysiological study was performed on anesthetized rabbits before and after immunization and subsequent treatment with the RI peptide inhibitor. Each rabbit served as its own control.
  
  
  RESULTS
  No sustained arrhythmias were induced at preimmune baseline. At 6 weeks after immunization, there was a marked increase in induced sustained tachyarrhythmias, predominantly sinus tachycardia, which was largely suppressed by the RI peptide. The atrial effective refractory period was shortened significantly in immunized rabbits compared to their preimmune state. The RI peptide reversed and prolonged this shortening. β1AR antibody levels were negatively correlated with the atrial effective refractory period. Postimmune sera-induced β1AR activation in transfected cells in vitro was also blocked by the RI peptide.
  
  
  CONCLUSIONS
  β1AR-activating autoantibodies are associated with reduction of the atrial effective refractory period and facilitate arrhythmia induction in this model. The RI peptide reversal may have important therapeutic implications in subjects who harbor these autoantibodies.
authors.affiliation: Heart Rhythm Institute and Department of Medicine, University of Oklahoma Health Sciences Center and Veterans Affairs Medical Center, Oklahoma City, OK, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: Heart Rhythm Institute and Department of Medicine, University of Oklahoma Health Sciences Center and Veterans Affairs Medical Center, Oklahoma City, OK, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Heart Rhythm Institute and Department of Medicine, University of Oklahoma Health Sciences Center and Veterans Affairs Medical Center, Oklahoma City, OK, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.affiliation: Heart Rhythm Institute and Department of Medicine, University of Oklahoma Health Sciences Center and Veterans Affairs Medical Center, Oklahoma City, OK, USA.
authors.forename: Vineet
authors.initials: V
authors.lastname: Veitla
authors.affiliation: Heart Rhythm Institute and Department of Medicine, University of Oklahoma Health Sciences Center and Veterans Affairs Medical Center, Oklahoma City, OK, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Scherlag
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Madeleine W
authors.initials: MW
authors.lastname: Cunningham
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Aston
authors.affiliation: Heart Rhythm Institute and Department of Medicine, University of Oklahoma Health Sciences Center and Veterans Affairs Medical Center, Oklahoma City, OK, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Kem
authors.affiliation: Heart Rhythm Institute and Department of Medicine, University of Oklahoma Health Sciences Center and Veterans Affairs Medical Center, Oklahoma City, OK, USA. xichun-yu@ouhsc.edu.|Heart Rhythm Institute, University of Oklahoma Health Sciences Center, TCH 6E103, 1200 Everett Drive, Oklahoma City, OK, 73104, USA. xichun-yu@ouhsc.edu.
authors.forename: Xichun
authors.initials: X
authors.lastname: Yu
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000276:immunology* / Q000517:prevention & control*; D001323:Autoantibodies / Q000276:immunology*; D040761:Biomimetic Materials / Q000008:administration & dosage; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001323:Autoantibodies; D010455:Peptides; D018342:Receptors, Adrenergic, beta-1
keywords: Acetylcholine; Activating autoantibodies; Rabbit; Retro-inverso peptide; Tachyarrhythmias; β1-Adrenergic receptor