Investigating the mechanisms of drug interaction

An in-silico model for pharmacotherapy

Investigating drug interaction, under hypoxia conditions with and without pro-arrhythmic comorbidity.

A transmural anisotropic ventricular tissue model consists of endocardial, mid-myocardial, and epicardial myocytes which are configured to investigate drug interaction, such as Hydroxychloroquine (HCQ), under hypoxia conditions without and with pro-arrhythmic comorbidity. In the ventricular model, HCQ has a trivial effect on hypoxia, except in the combination of mild hypoxia with moderate hypokalemia and severe hypoxia with mild hypokalemia, where it initiates reentrant arrhythmia. Secondly, incorporating drug dosage variations indicates 10 μM HCQ for all settings except in severe hypoxia conditions where reentrant arrhythmia occurred.

The protocol influences the appearance of reentrant arrhythmia for severe hypoxia with 10 μM HCQ dosage. For other conditions, including tachycardiac pacing protocol, no arrhythmia occurred. These findings infer that the arrhythmic fatality rate can be alleviated by altering the dosage of HCQ and can aid in the treatment of hypoxia-induced symptoms caused by COVID-19.

The author would like to thank Dr Ponnuraj Kirthi Priya for her outstanding contribution to this research-led article. Dr. Kirthi was a Scientist at DMMT, TCS, and had completed her Ph.D. from IIT Madras.