Autoantibodies with beta-adrenergic activity from chronic chagasic patients induce cardiac arrhythmias and early afterdepolarization in a drug-induced LQT2 rabbit hearts.

BACKGROUND

Cardiac arrhythmias are one of the main causes of death in ChCP and other dilated cardiomyopathies. Previous studies demonstrated that ventricular arrhythmias are associated with the presence of autoantibodies with beta-adrenergic activity, Ab-β.

OBJECTIVES

The aim of this study was to investigate whether Ab-β, present in chronic chagasic patients (ChCP), induce cardiac arrhythmias in the pharmacological type-2 long QT syndrome model (LQTS-2).

METHODS/RESULTS: The LQTS2 was established by perfusion of Tyrode saline solution with a potassium channel blocker E-4031 (5μM) in isolated rabbit hearts or in rabbit cardiac strips, in order to record ECG or action potential, respectively. Autoantibodies from ChCP activating (Ab-β) or not (Ab-NR) cardiac beta 1-adrenergic receptors were used. Ab-β, but not Ab-NR, were able to significantly shorten QT, QTc and increase Tpeak-Tend interval in the LQTS-2. A positive correlation between higher QTc and Tpeak-Tend was found after Ab-β perfusion in the same model. In addition, in the LQTS-2 model, in almost 75% (11/15) of the hearts perfused with Ab-β, ventricular and atrio-ventricular electrical disturbances were observed. Atenolol abolished all Ab-β-induced arrhythmias. Ab-β, when perfused in a cellular LQTS-2, drastically reduced the action potential duration and evoked early afterdepolarization (EAD's), while Ab-NR did not modulate the AP properties in the LQTS-2.

CONCLUSION

The results indicate that Ab-β were able to induce cardiac arrhythmias and EAD's. This phenomenon can explain, at least in part, the cellular mechanism of Ab-β-induced arrhythmias. Furthermore, atenolol is effective for the treatment of Ab-β-induced arrhythmias.