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The virtual heart as a platform for screening drug cardiotoxicity
Author(s) -
Yuan Yongfeng,
Bai Xiangyun,
Luo Cunjin,
Wang Kuanquan,
Zhang Henggui
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12996
Subject(s) - cardiotoxicity , drug , virtual screening , medicine , amiodarone , drug development , pharmacology , heart disease , qt interval , computer science , bioinformatics , cardiology , drug discovery , toxicity , biology , atrial fibrillation
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.