Drug-induced shortening of the electromechanical window is an effective biomarker for in silico prediction of clinical risk of arrhythmias.

ABSTRACT:

Background and purpose

Early identification of drug-induced cardiac adverse events is key in drug development. Human-based computer models are emerging as an effective approach, complementary to in vitro and animal models. Drug-induced shortening of the electromechanical window has been associated with increased risk of arrhythmias. This study investigates the potential of a cellular surrogate for the electromechanical window (EMw) for prediction of pro-arrhythmic cardiotoxicity, and its underlying ionic mechanisms, using human-based computer models.

Experimental approach

In silico drug trials for 40 reference compounds were performed, testing up to 100-fold the therapeutic concentrations (EFTPC_max ) and using a control population of human ventricular action poten

SUBMITTER: Passini E 

PROVIDER: S-EPMC6780030 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature