Abstract:

Patients suffering from the congenital Long-QT syndrome have been reported to react highly sensitive to the presence of beta-adrenergic agents that are produced by the sympathetic nervous system. In this work we used an anisotropic and electrophysiologically heterogeneous in- silico 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. beta-adrenergic tonus shortened the QT interval and increased transmural dispersion of repolarization. These findings were consistent with the experimental reports.