Abstract
Activating autoantibodies (AAb) to β-adrenergic receptors (βAR) are associated with atrial fibrillation in patients with Graves' disease. In the present study, we examined the interaction of thyroid hormone with β1/2AR-AAb in inducing atrial tachyarrhythmias in the rabbit. Immunization of rabbits with a β1AR or β2AR second extracellular loop peptide produced high titers of β1AR-AAb or β2AR-AAb. Thyroid hormone in combination with β1AR-AAb or β2AR-AAb induced a significant number of sustained sinus tachycardia and atrial tachycardia, respectively. Both combinations resulted in significantly increased inductions of sustained arrhythmias compared to AAb alone. Thyroid hormone alone induced sustained sinus and junctional tachycardia. Sera from immunized rabbits specifically bound to and activated β1AR or β2AR in transfected cells in vitro. This study demonstrates thyroid hormone qualitatively accentuates the specific arrhythmogenic action of these AAb and quantitatively enhances their rate. Our data support a dual role of AAb and thyroid hormone in Graves'-associated tachyarrhythmias.