Simulating the effect of sodium channel blockage on cardiac electromechanics

Abstract

There is growing interest to better understand drug-induced cardiovascular complications and to predict undesirable side effects at as early a stage in the drug development process as possible. The purpose of this paper is to investigate computationally the influence of sodium ion channel blockage on cardiac electromechanics. To do so, we implement a myofiber orientation dependent passive stress model (Holzapfel-Ogden) in the multiphysics solver Chaste to simulate an imaged physiological model of the human ventricles. A dosage of a sodium channel blocker was then applied and its inhibitory effects on the electrical propagation across ventricles were modeled. We employ the Kerckhoffs active stress model to generate electrically excited contractile behavior of myofibers. Our predictions indicate that a delay in the electrical activation of ventricular tissue caused by the sodium channel blockage translates to a delay in the mechanical biomarkers that were investigated. Moreover, sodium channel blockage was found to increase left ventricular twist. A multiphysics computational framework from the cell level to the organ level was thus used to predict the effect of sodium channel blocking drugs on cardiac electromechanics.

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