In:
Experimental Physiology, Wiley, Vol. 102, No. 1 ( 2017-01), p. 25-33
Abstract:
What is the central question of this study? High titres of autoantibodies against the second extracellular loop of the β 1 ‐adrenergic receptor (β 1 ‐AAs) can be detected in the sera of patients with ventricular arrhythmias, but a causal relationship between β 1 ‐AAs and ventricular arrhythmias has not been established. What is the main finding and its importance? Monoclonal β 1 ‐AAs (β 1 ‐AR mAbs) were used in the experiments. We showed that β 1 ‐AR mAbs increased susceptibility to ventricular arrhythmias and induced repolarization abnormalities. Antibody adsorption of β 1 ‐AAs will be a potential new therapeutic strategy for ventricular arrhythmias in patients with high titres of β 1 ‐AAs. High titres of autoantibodies against the second extracellular loop of the β 1 ‐adrenergic receptor (β 1 ‐AAs) can be detected in sera from patients with ventricular arrhythmias, but a causal relationship between β 1 ‐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 β 1 ‐adrenergic receptor (β 1 ‐AR mAbs) were used in all experiments. The results showed that β 1 ‐AR mAbs induced premature ventricular contractions in guinea‐pigs and isolated guinea‐pig hearts. In addition, β 1 ‐AR mAbs decreased the threshold of VT/VF and prolonged the duration of VT/VF. Furthermore, β 1 ‐AR mAbs shortened the corrected QT interval and effective refractory period, and prolonged late‐phase repolarization of the monophasic action potential (MAPD 90−30 ). These changes in electrophysiological parameters might be attributed, at least in part, to the arrhythmogenicity of β 1 ‐AR mAbs.
Type of Medium:
Online Resource
ISSN:
0958-0670
,
1469-445X
DOI:
10.1113/eph.2017.102.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
1493802-9
