In-silico evaluation of β-adrenergic effects on the Long-QT syndrome

Patients suffering from the congenital Long-QT syndrome have been reported to react highly sensitive to the presence of β-adrenergic agents that are produced by the sympathetic nervous system. In this work we used an anisotropic and electrophysiologically heterogeneous insilico model to reproduce wedge experiments in which the Long-QT syndrome was induced pharmacologically. The integration of an intracellular signaling cascade allowed the prediction of the effects of adrenergic agents on the different subtypes of the Long-QT syndrome. For LQT1 the in-silico model predicted a QT prolongation in the transmural pseudo ECG without an increase in transmural dispersion of repolarization. For LQT2 and LQT3 the QT prolongation was accompanied by an increased transmural dispersion of repolarization. β-adrenergic tonus shortened the QT interval and increased transmural dispersion of repolarization. These findings were consistent with the experimental reports.