title: The virtual heart as a platform for screening drug cardiotoxicity.
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.
authors.affiliation: School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Xiangyun
authors.initials: X
authors.lastname: Bai
authors.affiliation: School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Cunjin
authors.initials: C
authors.lastname: Luo
authors.affiliation: School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Kuanquan
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.|Biological Physics Group, School of Physics and Astronomy, The University of Manchester, Manchester, UK.
authors.forename: Henggui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D066126:Cardiotoxicity; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D018675:Toxicity Tests / Q000379:methods*