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| Campo DC | Valor | Lengua/Idioma |
|---|---|---|
| dc.contributor.author | Monasterio, Violeta | - |
| dc.contributor.author | Pueyo, Esther | - |
| dc.contributor.author | Carro, Jesús | - |
| dc.contributor.author | Rodríguez-Matas, José Félix | - |
| dc.date.accessioned | 2023-01-09T10:57:20Z | - |
| dc.date.available | 2023-01-09T10:57:20Z | - |
| dc.date.issued | 2022-11 | - |
| dc.identifier.issn | 0169-2607 | en_US |
| dc.identifier.uri | https://repositorio.usj.es/handle/123456789/887 | - |
| dc.description | Background 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 cost | en_US |
| dc.format.extent | 7 pag. | en_US |
| dc.format.mimetype | application/pdf | en_US |
| dc.language.iso | eng | en_US |
| dc.publisher | Elsevier | en_US |
| dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
| dc.subject | Cardiac electrophysiological models | en_US |
| dc.subject | Multi-scale simulations | en_US |
| dc.subject | Stimulus current | en_US |
| dc.title | Cardiac cells stimulated with an axial current-like waveform reproduce electrophysiological properties of tissue fibers | en_US |
| dc.type | info:eu-repo/semantics/article | en_US |
| dc.identifier.doi | https://doi.org/10.1016/j.cmpb.2022.107121 | en_US |
| dc.rights.accessrights | info:eu-repo/semantics/openAccess | en_US |
| Aparece en las colecciones: | Artículos de revistas | |
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| Fichero | Descripción | Tamaño | Formato | |
|---|---|---|---|---|
| cardiac cells stimulated.pdf | 914,75 kB | Adobe PDF |  Visualizar/Abrir |
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