Please use this identifier to cite or link to this item: https://repositorio.usj.es/handle/123456789/887

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dc.contributor.authorMonasterio, Violeta-
dc.contributor.authorPueyo, Esther-
dc.contributor.authorCarro, Jesús-
dc.contributor.authorRodríguez-Matas, José Félix-
dc.date.accessioned2023-01-09T10:57:20Z-
dc.date.available2023-01-09T10:57:20Z-
dc.date.issued2022-11-
dc.identifier.issn0169-2607en_US
dc.identifier.urihttps://repositorio.usj.es/handle/123456789/887-
dc.descriptionBackground and objective: In silico electrophysiological models are generally validated by comparing sim- ulated results with experimental data. When dealing with single-cell and tissue scales simultaneously, as occurs frequently during model development and calibration, the effects of inter-cellular coupling should be considered to ensure the trustworthiness of model predictions. The hypothesis of this paper is that the cell-tissue mismatch can be reduced by incorporating the effects of conduction into the single-cell stimulation current. Methods: Five different stimulation waveforms were applied to the human ven- tricular O’Hara-Rudy cell model. The waveforms included the commonly used monophasic and biphasic (symmetric and asymmetric) pulses, a triangular waveform and a newly proposed asymmetric waveform (stimulation A) that resembles the transmembrane current associated with AP conduction in tissue. A comparison between single-cell and fiber simulated results was established by computing the relative difference between the values of AP-derived properties at different scales, and by evaluating the differ- ences in the contributions of ionic conductances to each evaluated property. As a proof of the benefit, we investigated multi-scale differences in the simulation of the effects induced by dofetilide, a selective I Kr blocker with high torsadogenic risk, on ventricular repolarization at different pacing rates. Results: Out of the five tested stimulation waveforms, stimulation A produced the closest correspondence between cell and tissue simulations in terms of AP properties at steady-state and under dynamic pacing and of ionic contributors to those AP properties. Also, stimulation A reproduced the effects of dofetilide better than the other alternative waveforms, mirroring the ’beat-skipping’ behavior observed at fast pacing rates in experiments with human tissue. Conclusions: The proposed stimulation current waveform accounts for inter-cellular coupling effects by mimicking cell excitation during AP conduction. The proposed wave- form improves the correspondence between simulation scales, which could improve the trustworthiness of single-cell simulations without adding computational costen_US
dc.format.extent7 pag.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCardiac electrophysiological modelsen_US
dc.subjectMulti-scale simulationsen_US
dc.subjectStimulus currenten_US
dc.titleCardiac cells stimulated with an axial current-like waveform reproduce electrophysiological properties of tissue fibersen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dc.identifier.doihttps://doi.org/10.1016/j.cmpb.2022.107121en_US
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessen_US
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