In silico Assessment of Antiarrhythmic Effects of Drug Ranolazine on Electrical Activity in Human Ventricular Myocardium

摘要

The aim of this study was to simulate the electrophysiological modifications by the ranolazine at the left ventricular wall level by using in vitro electrophysiological measurements from canine ventricular myocytes to generate early information on cardiac safety in the human heart. The antiarrhythmic effect of ranolazine on two proarrhythmic drugs was examined. The sensitivity of ionic currents to ranolazine was described as Action Potential Duration (APD) variations in response to different therapeutic concentrations. The observed results can be explained by the interplay between inhibition of the I_(NaL) and I_(Kr) currents. Simulation results are in agreement with in vitro and in vivo studies of arrhythmia and confirmed the antiarrhythmic properties of ranolazine which may be utilized for suppressing ventricular arrhythmias.