The virtual heart as a platform for screening drug cardiotoxicity.

Yongfeng Yuan, Xiangyun Bai, Cunjin Luo, Kuanquan Wang, Henggui Zhang

    Research output: Contribution to journalArticlepeer-review


    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.
    Original languageEnglish
    JournalBritish Journal of Pharmacology
    Issue number23
    Publication statusPublished - 3 Nov 2014


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