000075795 001__ 75795 000075795 005__ 20210820090345.0 000075795 0247_ $$2doi$$a10.1371/journal.pone.0204411 000075795 0248_ $$2sideral$$a108351 000075795 037__ $$aART-2018-108351 000075795 041__ $$aeng 000075795 100__ $$0(orcid)0000-0001-7789-2973$$aCarro, J. 000075795 245__ $$aA response surface optimization approach to adjust ionic current conductances of cardiac electrophysiological models. Application to the study of potassium level changes 000075795 260__ $$c2018 000075795 5060_ $$aAccess copy available to the general public$$fUnrestricted 000075795 5203_ $$aCardiac electrophysiological computational models are often developed from previously published models. The new models may incorporate additional features to adapt the model to a different species or may upgrade a specific ionic formulation based on newly available experimental data. A relevant challenge in the development of a new model is the estimation of certain ionic current conductances that cannot be reliably identified from experiments. A common strategy to estimate those conductances is by means of constrained non-linear least-squares optimization. In this work, a novel methodology is proposed for estimation of ionic current conductances of cardiac electrophysiological models by using a response surface approximation-based constrained optimization with trust region management. Polynomial response surfaces of a number of electrophysiological markers were built using statistical sampling methods. These markers included action potential duration (APD), triangulation, diastolic and systolic intracellular calcium concentration, and time constants of APD rate adaptation. The proposed methodology was applied to update the Carro et al. human ventricular action potential model after incorporation of intracellular potassium ([K+]i) dynamics. While the Carro et al. model was well suited for investigation of arrhythmogenesis, it did not allow simulation of [K+]i changes. With the methodology proposed in this study, the updated Carro et al. human ventricular model could be used to simulate [K+]i changes in response to varying extracellular potassium ([K+]o) levels. Additionally, it rendered values of evaluated electrophysiological markers within physiologically plausible ranges. The optimal values of ionic current conductances in the updated model were found in a notably shorter time than with previously proposed methodologies. As a conclusion, the response surface optimization-based approach proposed in this study allows estimating ionic current conductances of cardiac electrophysiological computational models while guaranteeing replication of key electrophysiological features and with an important reduction in computational cost with respect to previously published approaches. The updated Carro et al. model developed in this study is thus suitable for the investigation of arrhythmic risk-related conditions, including those involving large changes in potassium concentration. 000075795 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/DPI2016-75458-R$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 638284-MODELAGE$$9info:eu-repo/grantAgreement/EC/H2020/638284/EU/Is your heart aging well? A systems biology approach to characterize cardiac aging from the cell to the body surface/MODELAGE$$9info:eu-repo/grantAgreement/ES/DGA/T24-17R$$9info:eu-repo/grantAgreement/ES/DGA-FEDER/T39-17R-BSICoS 000075795 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000075795 590__ $$a2.776$$b2018 000075795 591__ $$aMULTIDISCIPLINARY SCIENCES$$b23 / 69 = 0.333$$c2018$$dQ2$$eT2 000075795 592__ $$a1.1$$b2018 000075795 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2018$$dQ1 000075795 593__ $$aMedicine (miscellaneous)$$c2018$$dQ1 000075795 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2018$$dQ1 000075795 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000075795 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, E.$$uUniversidad de Zaragoza 000075795 700__ $$0(orcid)0000-0001-7612-266X$$aRodriguez Matas, J.F.$$uUniversidad de Zaragoza 000075795 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac. 000075795 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est. 000075795 773__ $$g13, 10 (2018), e0204411[23 pp]$$pPLoS One$$tPloS one$$x1932-6203 000075795 8564_ $$s6328201$$uhttps://zaguan.unizar.es/record/75795/files/texto_completo.pdf$$yVersión publicada 000075795 8564_ $$s113154$$uhttps://zaguan.unizar.es/record/75795/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000075795 909CO $$ooai:zaguan.unizar.es:75795$$particulos$$pdriver 000075795 951__ $$a2021-08-20-08:37:44 000075795 980__ $$aARTICLE