Research Repository

The virtual heart as a platform for screening drug cardiotoxicity

Yuan, Yongfeng and Bai, Xiangyun and Luo, Cunjin and Wang, Kuanquan and Zhang, Henggui (2015) 'The virtual heart as a platform for screening drug cardiotoxicity.' British Journal of Pharmacology, 172 (23). 5531 - 5547. ISSN 0007-1188

[img]
Preview
Text
bph.12996.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (2MB) | Preview

Abstract

To predict the safety of a drug at an early stage in its development is a major challenge as there is a lack of in vitro heart models that correlate data from preclinical toxicity screening assays with clinical results. A biophysically detailed computer model of the heart, the virtual heart, provides a powerful tool for simulating drug–ion channel interactions and cardiac functions during normal and disease conditions and, therefore, provides a powerful platform for drug cardiotoxicity screening. In this article, we first review recent progress in the development of theory on drug–ion channel interactions and mathematical modelling. Then we propose a family of biomarkers that can quantitatively characterize the actions of a drug on the electrical activity of the heart at multi‐physical scales including cellular and tissue levels. We also conducted some simulations to demonstrate the application of the virtual heart to assess the pro‐arrhythmic effects of cisapride and amiodarone. Using the model we investigated the mechanisms responsible for the differences between the two drugs on pro‐arrhythmogenesis, even though both prolong the QT interval of ECGs. Several challenges for further development of a virtual heart as a platform for screening drug cardiotoxicity are discussed.

Item Type: Article
Divisions: Faculty of Science and Health > Computer Science and Electronic Engineering, School of
Depositing User: Elements
Date Deposited: 03 Mar 2021 10:52
Last Modified: 03 Mar 2021 10:52
URI: http://repository.essex.ac.uk/id/eprint/29991

Actions (login required)

View Item View Item