β1-adrenoceptor autoantibodies increase the susceptibility of ventricular arrhythmias involving abnormal repolarization in guinea pigs

High titers of autoantibodies against the second extracellular loop of β₁-adrenergic receptors (β₁-AA) can be detected in the sera from patients with ventricular arrhythmias, but a causal relationship between β₁-AAs and ventricular arrhythmias has not been established. In this work, electrocardiograms 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. Monophasic action potential and effective refractory period (ERP) of the left ventricle were recorded in the paced isolated guinea pig hearts. What's more, to increase the specificity, monoclonal autoantibodies against the second extracellular loop of β₁-adrenergic receptor (β₁-AR mAb) had been used in all experiments. The results showed that β₁-AR mAbs induced premature ventricular contractions (PVC) in guinea pigs and isolated guinea pig hearts. In addition, β₁-AR mAbs decreased the threshold of VT/VF and prolonged the VT/VF duration. Furthermore, β₁-AR mAbs shortened corrected QT interval (QT_c) and ERP, 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 β₁-AR mAbs.

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