A peptidomimetic inhibitor suppresses the inducibility of β1-adrenergic autoantibody-mediated cardiac arrhythmias in the rabbit. J Interv Card Electrophysiol 2015 Dec;44(3):205-12
Date
10/09/2015Pubmed ID
26446828Pubmed Central ID
PMC5812008DOI
10.1007/s10840-015-0063-8Scopus ID
2-s2.0-84947128203 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
PURPOSE: 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.
Author List
Li H, Zhang L, Huang B, Veitla V, Scherlag BJ, Cunningham MW, Aston CE, Kem DC, Yu XAuthor
Vineet Veitla MBBS Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adrenergic beta-1 Receptor AntagonistsAnimals
Arrhythmias, Cardiac
Autoantibodies
Biomimetic Materials
Peptides
Rabbits
Receptors, Adrenergic, beta-1
Signal Transduction
Treatment Outcome
