Three-Dimensional Heart Model-Based Screening of Proarrhythmic Potential by in silico Simulation of Action Potential and Electrocardiograms.

ABSTRACT: The proarrhythmic risk is a major concern in drug development. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative has proposed the JTpeak interval on electrocardiograms (ECGs) and qNet, an in silico metric, as new biomarkers that may overcome the limitations of the hERG assay and QT interval. In this study, we simulated body-surface ECGs from patch-clamp data using realistic models of the ventricles and torso to explore their suitability as new in silico biomarkers for cardiac safety. We tested seven drugs in this study: dofetilide (high proarrhythmic risk), ranolazine, verapamil (QT increasing, but safe), bepridil, cisapride, mexiletine, and diltiazem. Human ventricular geometry was reconstructed from computed tomography (CT) images, and a Purkinje fiber network was mapped o

SUBMITTER: Hwang M 

PROVIDER: S-EPMC6738014 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature