RAPHEL, Fabien; BOULAKIA, Muriel; ZEMZEMI, Nejib; COUDIÈRE, Yves; GUILLON, Jean-Michel; ZITOUN, Philippe; GERBEAU, Jean-Frédéric

doi:10.1109/TBME.2017.2748798

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RAPHEL, Fabien
Numerical simulation of biological flows [REO]

BOULAKIA, Muriel
Numerical simulation of biological flows [REO]

ZEMZEMI, Nejib
Modélisation et calculs pour l'électrophysiologie cardiaque [CARMEN]

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Article de revue

Ce document a été publié dans

IEEE Transactions on Biomedical Engineering. 2018, vol. 65, n° 6, p. 1311-1319

Institute of Electrical and Electronics Engineers

Résumé en anglais

Objective: Multi Electrodes Arrays (MEAs) combined with cardiomy-ocytes derived from human induced pluripotent stem cells (hiPSC-CMs) can enable high-or medium-throughput drug screening in safety pharma-cology. This technology has recently attracted a lot of attention, in particular from an international initiative named CiPA. But it is currently limited by the difficulty to analyze the measured signals. We propose a strategy to analyze the signals acquired by the MEA and to automatically deduce the channels affected by the drug. Methods: Our method is based on the bidomain equations, a model for the MEA electrodes, and an inverse problem strategy. Results: In silico MEA signals are obtained for two commercial devices and an example of Early After Depolarization (EAD) is presented. Then, by processing real signals obtained for four different compounds, our algorithm was able to provide dose-response curves for potassium, sodium and calcium channels. For ivabradine and moxifloxacin, the IC50 and dose-response curves are in very good agreement with known values. Significance: The proposed strategy offers a possible answer to a major question raised by the community of safety pharmacology. By allowing a more automated analysis of the signals, our approach could contribute to promote the technology based on MEA and hiPSC-CMs, and therefore improve reliability and efficiency of drug screening.< Réduire

Mots clés en anglais

Cardiac Electrophysiology.

Multi Electrodes Arrays

Safety pharmacology

URI

https://oskar-bordeaux.fr/handle/20.500.12278/193603

DOI

http://dx.doi.org/10.1109/TBME.2017.2748798

Project ANR

Modélisation, simulation et traitement du signal en électrophysiologie cardiaque - ANR-13-LAB1-0007
Agency for mathematics in interaction with enterprise and society - ANR-10-LABX-0002

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Importé de hal

Unités de recherche

Institut de Mathématiques de Bordeaux (IMB) - UMR 5251