Abstract 14552: Effect of Beita1-AA on Heart Failure: An Increased Sensitivity of Arrhythmia
Existing research found that the titer of autoantibodies against the second extracellular loop of β1-adrenoceptors (β1-adrenoceptors autoantibody, β1-AA) was higher in the heart failure (HF) patients, which was a potential injury factor. Yet, the relationship between the autoanbibodies and the increased arrhythmia susceptibility in HF patients is unclear. In this study, we assessed the hypothesis that β1-AA may contribute to the increased sensitivity of arrhythmia in HF mice. 108 patients of heart disease with arrhythmia were recruited. β1-AA was detected by ELISA. The sera from HF patients with a high β1-AA O.D. value were mixed together. The IgGs from β1-AA-positive patients were purified by a Mab TrapTM Kit, then administered to normal mice. ECGs were monitored. β1-AA monoclonal antibodies against a peptide corresponding to the second extracellular loop of β1-adrenoceptor were raised in BALB/c mice and performed using hybridoma then administered to HF mice. It was shown that in arrhythmia group the titer of autoantibody was significant higher than control group (0.285±0.096vs.0.135±0.124, P<0.01), and in arrhythmia group with heart disease, the titer was significantly higher than heart disease group (0.324±0.084vs.0.231±0.085, P<0.05). Meanwhile, arrhythmia frequency was shown to be increased after injection of β1-AA than before (7.00±2.196vs.2.50±0.173, P<0.05, n=6). Furthermore, β1-AA monoclonal antibodies induced a dose-dependent increase of arrhythmia frequency in HF mice, which was significantly higher than the normal group (45.00±6.351vs.21.00±2.646, P<0.05, n=6).The frequency of ventricular arrhythmia was much more than other types (36.50±3.728vs.11.50±3.271; 36.50±3.728vs.6.67±2.160,*P<0.05 versus atrial arrhythmia, #P<0.05 versus conductive arrhythmia, n=6). Compared with the β1-AA group, arrhythmia was decreased (12.67± 1.453 vs.7.667±1.202, P=0.0569, n=6) in the pretreatment of metoprolol which is a selective β11-adrenergic receptor blocker. And in HF group pretreated by metoprolol, arrhythmia was significant decreased (45.00± 6.351 vs.24.33±3.712,P<0.05, n=6) than the β1-AA individually treated HF group. In conclusion, β1-AA may contribute to the increased ventricular arrhythmia sensitivity in HF.
- © 2013 by American Heart Association, Inc.