A High Fidelity Transmural Anisotropic Ventricular Tissue Model Function to Investigate the Interaction Mechanisms of Drug: An In-Silico Model for Pharmacotherapy

Abstract

A high fidelity transmural anisotropic ventricular tissue model consisting of endocardial, mid myocardial, and epicardial myocytes were configured to investigate drug interaction, such as Hydroxychloroquine (HCQ), under hypoxia conditions without and with pro-arrhythmic comorbidity like hypokalemia in (a) ventricular tissue b) its arrhythmogenesis for different dosages and (b) two different pacing sequences (Normal and tachycardiac). In-silico ventricular modeling indicates HCQ has an insignificant effect on hypoxia with and without comorbidities, except in the combination of mild hypoxia with moderate hypokalemia condition and severe hypoxia with mild hypokalemia where it initiated a re-entrant arrhythmia. Secondly, incorporating drug dosage variations indicates the 10 μM HCQ created PVCs for all settings except in severe hypoxia conditions where re-entrant arrhythmia occurred. In addition to the dosage of HCQ utilized for treatment, the pacing protocol also influences the appearance of re-entrant arrhythmia only for severe hypoxia with 10 μM HCQ dosage alone. For all other conditions, including tachycardiac pacing protocol, no arrhythmia occurred. These findings infer that the arrhythmic fatality rate due to HCQ treatment for hypoxia can be effectively alleviated by subtly altering or personalizing the dosage of HCQ and aid in the treatment of hypoxia-induced symptoms caused by COVID.