ZEMZEMI, Nejib; BERNABEU, Miguel Oscar; SAIZ RODRIGUEZ, Javier; COOPER, Jonathan; PATHMANATHAN, Pras; MIRAMS, Gary; PITT-FRANCIS, Joe; BLANCA, Rodriguez

doi:10.1111/j.1476-5381.2012.02200.x

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

BERNABEU, Miguel Oscar
Computing Science Laboratory - Oxford University

SAIZ RODRIGUEZ, Javier
Universitat Politècnica de València = Universitad Politecnica de Valencia = Polytechnic University of Valencia [UPV]

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Article de revue

Ce document a été publié dans

British Journal of Pharmacology. 2012-10-01, vol. 168, n° 3, p. 718-733

Wiley

Résumé en anglais

This work is based on the computational models describing the physiology of the electrical wave propagation in the heart. The goal is to show the ability of computational models to reproduce the effect drugs on the electrical activity of the heart at the cell, the organ (heart) and the ECG body surface potential levels. We use the state-of-the-art mathematical models governing the heart electrical activity. The drug model is introduced using an ion channel conductance block for both hERG and sodium depending on the IC50 value and the drug dose. We measure the ECG at the surface and compare the different biomarkers. Introducing a 50% hERG block results in 7.8% prolongation of the APD90 and 5.7% QT interval prolongation, whereas the hERG block does not affect the QRS interval. Introducing 50% of sodium block prolongs the QRS and the QT intervals respectively by 12% and 5% and delays the activation times, whereas the sodium block does not affect the APD90. Both potassium and sodium blocks prolong the QT interval, but the reason behind is different: For the first it is due to APD prolongation, while for the second it is due to a reduction of the electrical wave velocity. This example of study shows the usability of the in silco models in the investigation of drugs mechanism and the assessment of drug side effects.< Réduire

Mots clés en anglais

QRS Widening

ECG modelling

Computer simulation

Drug

HERG

Sodium blockers

QT prolongation

URI

https://oskar-bordeaux.fr/handle/20.500.12278/189752

DOI

http://dx.doi.org/10.1111/j.1476-5381.2012.02200.x

Projet Européen

Computational Prediction of Drug Cardiac Toxicity

Origine

Importé de hal

Unités de recherche

Institut de Mathématiques de Bordeaux (IMB) - UMR 5251