ß1 -Adrenoceptor autoantibodies increase the susceptibility to ventricular arrhythmias involving abnormal repolarization in guinea-pigs.
Exp Physiol
; 102(1): 25-33, 2017 01 01.
Article
em En
| MEDLINE
| ID: mdl-27862484
ABSTRACT
NEW FINDINGS:
What is the central question of this study? High titres of autoantibodies against the second extracellular loop of the ß1 -adrenergic receptor (ß1 -AAs) can be detected in the sera of patients with ventricular arrhythmias, but a causal relationship between ß1 -AAs and ventricular arrhythmias has not been established. What is the main finding and its importance? Monoclonal ß1 -AAs (ß1 -AR mAbs) were used in the experiments. We showed that ß1 -AR mAbs increased susceptibility to ventricular arrhythmias and induced repolarization abnormalities. Antibody adsorption of ß1 -AAs will be a potential new therapeutic strategy for ventricular arrhythmias in patients with high titres of ß1 -AAs. High titres of autoantibodies against the second extracellular loop of the ß1 -adrenergic receptor (ß1 -AAs) can be detected in sera from patients with ventricular arrhythmias, but a causal relationship between ß1 -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 ß1 -adrenergic receptor (ß1 -AR mAbs) were used in all experiments. The results showed that ß1 -AR mAbs induced premature ventricular contractions in guinea-pigs and isolated guinea-pig hearts. In addition, ß1 -AR mAbs decreased the threshold of VT/VF and prolonged the duration of VT/VF. Furthermore, ß1 -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 ß1 -AR mAbs.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Arritmias Cardíacas
/
Autoanticorpos
/
Fibrilação Ventricular
/
Taquicardia Ventricular
/
Receptores Adrenérgicos beta 1
/
Ventrículos do Coração
Limite:
Animals
Idioma:
En
Revista:
Exp Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China