Faculty Collaboration Database

β1-Adrenergic and M2 Muscarinic Autoantibodies and Thyroid Hormone Facilitate Induction of Atrial Fibrillation in Male Rabbits. Endocrinology 2016 Jan;157(1):16-22

Date

10/31/2015

Pubmed ID

26517045

DOI

10.1210/en.2015-1655

Scopus ID

2-s2.0-84954506000 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

Activating autoantibodies to the β1-adrenergic and M2 muscarinic receptors are present in a very high percentage of patients with Graves' disease and atrial fibrillation (AF). The objective of this study was to develop a reproducible animal model and thereby to examine the impact of these endocrine-like autoantibodies alone and with thyroid hormone on induction of thyroid-associated atrial tachyarrhythmias. Five New Zealand white rabbits were coimmunized with peptides from the second extracellular loops of the β1-adrenergic and M2 muscarinic receptors to produce both sympathomimetic and parasympathomimetic antibodies. A catheter-based electrophysiological study was performed on anesthetized rabbits before and after immunization and subsequent treatment with thyroid hormone. Antibody expression facilitated the induction of sustained sinus, junctional and atrial tachycardias, but not AF. Addition of excessive thyroid hormone resulted in induced sustained AF in all animals. AF induction was blocked acutely by the neutralization of these antibodies with immunogenic peptides despite continued hyperthyroidism. The measured atrial effective refractory period as one parameter of AF propensity shortened significantly after immunization and was acutely reversed by peptide neutralization. No further decrease in the effective refractory period was observed after the addition of thyroid hormone, suggesting other cardiac effects of thyroid hormone may contribute to its role in AF induction. This study demonstrates autonomic autoantibodies and thyroid hormone potentiate the vulnerability of the heart to AF, which can be reversed by decoy peptide therapy. These data help fulfill Witebsky's postulates for an increased autoimmune/endocrine basis for Graves' hyperthyroidism and AF.

Author List

Li H, Murphy T, Zhang L, Huang B, Veitla V, Scherlag BJ, Kem DC, Yu X

Author

Vineet Veitla MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenergic beta-1 Receptor Agonists
Animals
Antigens
Atrial Fibrillation
Autoantibodies
Coronary Sinus
Disease Models, Animal
Graves Disease
Heart Atria
Heart Conduction System
Male
Muscarinic Agonists
Peptide Fragments
Rabbits
Receptor, Muscarinic M2
Receptors, Adrenergic, beta-1
Refractory Period, Electrophysiological
Tachycardia
Thyroxine
Up-Regulation