title: β1-Adrenoceptor autoantibodies increase the susceptibility to ventricular arrhythmias involving abnormal repolarization in guinea-pigs.
abstract: What is the central question of this study? High titres of autoantibodies against the second extracellular loop of the β1-adrenergic receptor (β1-AAs) can be detected in the sera of patients with ventricular arrhythmias, but a causal relationship between β1-AAs and ventricular arrhythmias has not been established. What is the main finding and its importance? Monoclonal β1-AAs (β1-AR mAbs) were used in the experiments. We showed that β1-AR mAbs increased susceptibility to ventricular arrhythmias and induced repolarization abnormalities. Antibody adsorption of β1-AAs will be a potential new therapeutic strategy for ventricular arrhythmias in patients with high titres of β1-AAs. High titres of autoantibodies against the second extracellular loop of the β1-adrenergic receptor (β1-AAs) can be detected in sera from patients with ventricular arrhythmias, but a causal relationship between β1-AAs and ventricular arrhythmias has not been established. In this work, ECGs of guinea-pigs and isolated guinea-pig hearts were recorded. Ventricular tachycardia (VT) and ventricular fibrillation (VF) were evoked by programmed electrical stimulation of the left ventricular epicardium of isolated guinea-pig hearts. The monophasic action potential and effective refractory period of the left ventricle were recorded in paced isolated guinea-pig hearts. Furthermore, to increase the specificity, monoclonal autoantibodies against the second extracellular loop of the β1-adrenergic receptor (β1-AR mAbs) were used in all experiments. The results showed that β1-AR mAbs induced premature ventricular contractions in guinea-pigs and isolated guinea-pig hearts. In addition, β1-AR mAbs decreased the threshold of VT/VF and prolonged the duration of VT/VF. Furthermore, β1-AR mAbs shortened the corrected QT interval and effective refractory period, and prolonged late-phase repolarization of the monophasic action potential (MAPD90-30). These changes in electrophysiological parameters might be attributed, at least in part, to the arrhythmogenicity of β1-AR mAbs.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.|Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Zhao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Huang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Du
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Shanxi Medical University, Shanxi, 030001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing, 100029, China.
authors.forename: Chang-Sheng
authors.initials: CS
authors.lastname: Ma
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Metabolic Disturbance Related Cardiovascular Disease, Beijing, 100069, China.
authors.forename: Hui-Rong
authors.identifier: 0000-0001-7942-0777
authors.initials: HR
authors.lastname: Liu
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology*; D001323:Autoantibodies / Q000097:blood*; D000075224:Cardiac Conduction System Disease / Q000378:metabolism / Q000503:physiopathology; D004562:Electrocardiography / Q000379:methods; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000378:metabolism / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010496:Pericardium / Q000378:metabolism / Q000503:physiopathology; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D012032:Refractory Period, Electrophysiological / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D014693:Ventricular Fibrillation / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D001323:Autoantibodies; D018342:Receptors, Adrenergic, beta-1
keywords: autoantibody; ventricular arrhythmia; β1-adrenoceptor