Abstract 2616: Facilitation of Triggered Firing in Superfused Canine Pulmonary Veins by Activating Antibodies to Beta Adrenergic and Muscarinic Receptors in Serum From Patients With Graves’ Disease
Background: Increased titers of antibodies activating beta-adrenergic and muscarinic-2 (M-2) receptors (ELISA assays) are present in the serum and purified immunoglobulins (IgG) of patients with Graves’ disease.
Methods: We obtained serum and purified IgG from 20 patients with Graves’ disease and documented presence of beta-adrenergic and M-2 receptor activating antibodies by ELISA assays. We examined the potential facilitatory role for beta-adrenergic and M-2 receptor activating antibodies, present in the serum and IgG of these patients, upon local autonomic nerve stimulation (0.1 msec stimuli, 100 Hz, 300 msec duration train) (LANS)-induced triggered firing (TF) and tachycardia-pause pacing-induced early after depolarization (EAD) formation, using intracellular microelectrode recordings from superfused canine pulmonary veins.
Results: Purified IgG (0.15 mg/ml) (n=14):
increased resting potential (RP) (p<0.05),
decreased action potential duration at 50% (APD50) and 90% (APD90) of repolarization (p<0.05),
enhanced the magnitude of EAD formation with tachycardia-pause pacing (p<0.01), and
decreased the stimulus voltage train needed to induced TF by LANS (p<0.001).
Both enhanced EAD formation and LANS-induced TF, induced by IgG, were blocked by atenolol (3.2 × 10−8 M). Hyperpolarization, action potential shortening, and LANS-induced TF, induced by IgG, were blocked by atropine (3.2 × 10−8 M). Similar results were also noted for 1:100 dilution of patient serum (n=6).
Conclusions: These data demonstrate a facilitatory role of beta-adrenergic (enhanced EAD formation) and M-2 receptor (hyperpolarization and APD shortening) activating antibodies for pacing-pause induced EAD formation and LANS-induced TF in canine pulmonary veins. Antibodies activating beta-adrenergic and M-2 receptors may be responsible in part for the high incidence of atrial fibrillation observed in patients with Graves’ disease.