Antibodies with beta-adrenergic activity from chronic chagasic patients modulate the QT interval and M cell action potential duration

Aims The aim of this study was to investigate whether the sera from chronic chagasic patients (CChPs) with beta-1 adrenergic activity (Ab-β) can modulate ventricular repolarization. Beta-adrenergic activity has been described in CChP. It increases the l-type calcium current and heart rate in isolated hearts, but its effects on ventricular repolarization has not been described. Methods and results In isolated rabbit hearts, under pacing condition, QT interval was measured under Ab-β perfusion. Beta-adrenergic activity was also tested in guinea pig ventricular M cells. Furthermore, the immunoglobulin fraction (IgG-β) of the Ab-β was tested on Ito, ICa, and Iks currents in rat, rabbit, and guinea pig myocytes, respectively. Beta-adrenergic activity shortened the QT interval. This effect was abolished in the presence of propranolol. In addition, sera from CChP without beta-adrenergic activity (Ab-β) did not modulate QT interval. The M cell action potential duration (APD) was reversibly shortened by Ab-β. Atenolol inhibited this effect of Ab-β, and Ab- did not modulate the AP of M cells. Ito was not modulated by isoproterenol nor by IgG-β. However, IgG-β increased ICa and IKs. Conclusion The shortening of the QT interval and APD in M cells and the increase of IKs and ICa induced by IgG-β contribute to repolarization changes that may trigger malignant ventricular arrhythmias observed in patients with chronic chagasic or idiopathic cardiomyopathy.