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Inducible Cardiac Arrhythmias Caused by Enhanced β1-adrenergic Autoantibody Expression in the Rabbit

Inducible Cardiac Arrhythmias Caused by Enhanced β1-adrenergic Autoantibody Expression in the Rabbit

Hongliang Li, Benjamin J Scherlag, David C Kem, Alexandria Benbrook, Xiaohua Shen, Madeleine W Cunningham, Ralph Lazzara, Christopher E Aston, Xichun Yu

Am J Physiol Heart Circ Physiol. 2014 Feb;306(3):H422-8.

PMID: 24271491

Abstract:

Previous studies demonstrated burst pacing and intravenous infusion of ACh induced sustained atrial tachycardia when rabbits were immunized to produce β2-adrenergic receptor (β2AR)-activating autoantibodies. The objective of this study was to examine the arrhythmogenic effect of β1-adrenergic receptor (β1AR)-activating autoantibodies in the rabbit. Eight New Zealand white rabbits were immunized with a β1AR second extracellular loop peptide to raise β1AR antibody titers. A catheter-based electrophysiological study was performed on anesthetized rabbits before and after immunization. Arrhythmia occurrence was determined in response to burst pacing before and after ACh infusion in incremental concentrations of 10 μM, 100 μM, and 1 mM. The baseline sinus heart rate before and after immunization averaged 149 ± 17 per min and 169 ± 16 per min, respectively (P < 0.05). In the preimmune studies, there were five sustained (≥10 s) arrhythmias in 32 induction attempts, which occurred in only four of eight rabbits. In the postimmune studies, there were 22 sustained arrhythmias in 32 induction attempts, which occurred in all eight rabbits (P < 0.0001 for the independent effect of immunization). Of the 22 sustained arrhythmias postimmunization, 15 were sinus tachycardia compared with only two before immunization (P < 0.01 for the independent effect of immunization). Postimmune (but not preimmune) rabbit sera demonstrated specific binding to β1AR and induced significant β1AR activation in transfected cells in vitro. No cross-reactivity with β2AR was observed. In conclusion, in contrast with rabbits with β2AR-activating autoantibodies that demonstrate predominantly atrial tachycardias, enhanced autoantibody activation of β1AR in the rabbit leads to tachyarrhythmias mainly in the form of sustained sinus tachycardia.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42417048	Anti-phospho-Integrin β1 (pThr789) antibody produced in rabbit			Price
IAR4248237	Anti-α2C Adrenergic Receptor antibody produced in rabbit			Price

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