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Computational assessment of drug-induced effects on the electrocardiogram: from ion channel to body surface potentials

hal.structure.identifierModélisation et calculs pour l'électrophysiologie cardiaque [CARMEN]
dc.contributor.authorZEMZEMI, Nejib
hal.structure.identifierComputing Science Laboratory - Oxford University
dc.contributor.authorBERNABEU, Miguel Oscar
hal.structure.identifierUniversitat Politècnica de València = Universitad Politecnica de Valencia = Polytechnic University of Valencia [UPV]
dc.contributor.authorSAIZ RODRIGUEZ, Javier
hal.structure.identifierComputing Science Laboratory - Oxford University
dc.contributor.authorCOOPER, Jonathan
hal.structure.identifierComputing Science Laboratory - Oxford University
dc.contributor.authorPATHMANATHAN, Pras
hal.structure.identifierComputing Science Laboratory - Oxford University
dc.contributor.authorMIRAMS, Gary
hal.structure.identifierComputing Science Laboratory - Oxford University
dc.contributor.authorPITT-FRANCIS, Joe
hal.structure.identifierComputing Science Laboratory - Oxford University
dc.contributor.authorBLANCA, Rodriguez
dc.date.accessioned2024-04-04T02:23:39Z
dc.date.available2024-04-04T02:23:39Z
dc.date.issued2012-10-01
dc.identifier.issn0007-1188
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/189752
dc.description.abstractEnThis 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.
dc.language.isoen
dc.publisherWiley
dc.subject.enQRS Widening
dc.subject.enECG modelling
dc.subject.enComputer simulation
dc.subject.enDrug
dc.subject.enHERG
dc.subject.enSodium blockers
dc.subject.enQT prolongation
dc.title.enComputational assessment of drug-induced effects on the electrocardiogram: from ion channel to body surface potentials
dc.typeArticle de revue
dc.identifier.doi10.1111/j.1476-5381.2012.02200.x
dc.subject.halSciences du Vivant [q-bio]/Sciences pharmaceutiques
dc.subject.halSciences du Vivant [q-bio]/Toxicologie
dc.subject.halMathématiques [math]/Equations aux dérivées partielles [math.AP]
dc.subject.halMathématiques [math]/Analyse numérique [math.NA]
dc.subject.halInformatique [cs]/Bio-informatique [q-bio.QM]
dc.subject.halSciences du Vivant [q-bio]/Bio-Informatique, Biologie Systémique [q-bio.QM]
dc.description.sponsorshipEuropeComputational Prediction of Drug Cardiac Toxicity
bordeaux.journalBritish Journal of Pharmacology
bordeaux.page718-733
bordeaux.volume168
bordeaux.hal.laboratoriesInstitut de Mathématiques de Bordeaux (IMB) - UMR 5251*
bordeaux.issue3
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-00764102
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-00764102v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=British%20Journal%20of%20Pharmacology&rft.date=2012-10-01&rft.volume=168&rft.issue=3&rft.spage=718-733&rft.epage=718-733&rft.eissn=0007-1188&rft.issn=0007-1188&rft.au=ZEMZEMI,%20Nejib&BERNABEU,%20Miguel%20Oscar&SAIZ%20RODRIGUEZ,%20Javier&COOPER,%20Jonathan&PATHMANATHAN,%20Pras&rft.genre=article


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