Abstract 13975: Sustained Arrhythmias Induced by Combinations of β-adrenergic autoantibodies and Thyroid Hormone in the Rabbit
Introduction: Previously we reported that a significant percentage of patients with Graves’ disease and concurrent atrial fibrillation (AF) have activating autoantibodies (AA) to β-adrenergic receptors (βARs). The interaction of thyroid hormone (T4) with these AA in inducing atrial tachyarrhythmias has not been described.
Methods: Nine New Zealand white rabbits (3-4 months in age) were immunized with a β1AR (n=4) or β2AR (n=5) second extracellular loop peptide to raise β1AR-AA or β2AR-AA titers. The animals were boosted with the same peptides at 2 and 4 weeks. At 6 weeks, the rabbits were injected with T4 (50 μg/kg/d) for 2 weeks. Four additional rabbits were treated with T4 alone. A catheter-based electrophysiological study was performed on anesthetized rabbits at pre-immune, post-immune (6 weeks) and post T4 (8 weeks) states. Arrhythmia occurrence was determined in response to burst pacing before and after acetylcholine (Ach) infusion in incremental concentrations of 10 μM, 100 μM and 300 μM.
Results: For a comparison between control and experimental states for the induction of a sustained atrial arrhythmia, we used a chi-square and Pearson test. T4+β1AR-AA induced 10/20 compared to 1/20 (preimmune) events of sustained sinus tachycardia (sus ST, p=0.008) and sus AF 7/20 vs. 1/20 (preimmune) (p=0.05); whereas T4+β2AR-AA induced only sus ST 10/16 vs 1/16 (preimmune) (p=0.0006). T4 alone induced sus ST in 7/12 events vs. 0/12 (preimmune) (p=0.003). Sera from immunized rabbits demonstrated specific binding to β1AR/β2AR and induced significant β1AR/β2AR activation in transfected cells in vitro compared to the pre-immune sera. No receptor cross-reactivity was observed.
Conclusions: T4 alone or in combination with β1AR-AA or β2AR-AA significantly manifested sustained sinus tachycardia. Moreover, T4 in combination with β1AR-AA induced sustained AF in a significant number of instances. In previous studies, using the same protocols, we found that β1AR-AA alone induced a significant number of sustained sinus tachycardia episodes while β2AR-AA alone induced significant numbers of sustained atrial tachycardia. Neither protocol alone induced sustained AF.
- © 2013 by American Heart Association, Inc.