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Br J Pharmacol. 2015 Dec;172(23):5531-47. doi: 10.1111/bph.12996. Epub 2015 Jan 13.

The virtual heart as a platform for screening drug cardiotoxicity.

Author information

1
School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.
2
Biological Physics Group, School of Physics and Astronomy, The University of Manchester, Manchester, UK.

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.

PMID:
25363597
PMCID:
PMC4667856
DOI:
10.1111/bph.12996
[Indexed for MEDLINE]
Free PMC Article

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