000099347 001__ 99347
000099347 005__ 20240912131720.0
000099347 0247_ $$2doi$$a10.7554/eLife.48890
000099347 0248_ $$2sideral$$a122793
000099347 037__ $$aART-2019-122793
000099347 041__ $$aeng
000099347 100__ $$aTomek, Jakub
000099347 245__ $$aDevelopment, calibration, and validation of a novel human ventricular myocyte model in health, disease, and drug block
000099347 260__ $$c2019
000099347 5060_ $$aAccess copy available to the general public$$fUnrestricted
000099347 5203_ $$aHuman-based modelling and simulations are becoming ubiquitous in biomedicalscience due to their ability to augment experimental and clinical investigations. Cardiacelectrophysiology is one of the most advanced areas, with cardiac modelling and simulation beingconsidered for virtual testing of pharmacological therapies and medical devices. Current modelspresent inconsistencies with experimental data, which limit further progress. In this study, wepresent the design, development, calibration and independent validation of a human-basedventricular model (ToR-ORd) for simulations of electrophysiology and excitation-contractioncoupling, from ionic to whole-organ dynamics, including the electrocardiogram. Validation basedon substantial multiscale simulations supports the credibility of the ToR-ORd model under healthyand key disease conditions, as well as drug blockade. In addition, the process uncovers newtheoretical insights into the biophysical properties of the L-type calcium current, which are criticalfor sodium and calcium dynamics. These insights enable the reformulation of L-type calciumcurrent, as well as replacement of the hERG current model
000099347 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000099347 590__ $$a7.08$$b2019
000099347 591__ $$aBIOLOGY$$b5 / 92 = 0.054$$c2019$$dQ1$$eT1
000099347 592__ $$a6.079$$b2019
000099347 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2019$$dQ1
000099347 593__ $$aNeuroscience (miscellaneous)$$c2019$$dQ1
000099347 593__ $$aMedicine (miscellaneous)$$c2019$$dQ1
000099347 593__ $$aImmunology and Microbiology (miscellaneous)$$c2019$$dQ1
000099347 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000099347 700__ $$aBueno-Orovio, Alfonso
000099347 700__ $$aPassini, Elisa
000099347 700__ $$aZhou, Xin
000099347 700__ $$0(orcid)0000-0003-3183-4107$$aMincholé, Ana$$uUniversidad de Zaragoza
000099347 700__ $$aBritton, Oliver
000099347 700__ $$aBartolucci, Chiara
000099347 700__ $$aSeveri, Stefano
000099347 700__ $$aShrier, Alvin
000099347 700__ $$aVirag, Laszlo
000099347 700__ $$aVarro, Andras
000099347 700__ $$aRodriguez, Blanca
000099347 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000099347 773__ $$g8 (2019), e48890 [48 pp.]$$peLife (Cambridge)$$teLife$$x2050-084X
000099347 8564_ $$s5307055$$uhttps://zaguan.unizar.es/record/99347/files/texto_completo.pdf$$yVersión publicada
000099347 8564_ $$s2587525$$uhttps://zaguan.unizar.es/record/99347/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000099347 909CO $$ooai:zaguan.unizar.es:99347$$particulos$$pdriver
000099347 951__ $$a2024-09-12-13:15:37
000099347 980__ $$aARTICLE