Development, calibration, and validation of a novel human ventricular myocyte model in health, disease, and drug block

Tomek, Jakub ; Bueno-Orovio, Alfonso ; Passini, Elisa ; Zhou, Xin ; Mincholé, Ana (Universidad de Zaragoza) ; Britton, Oliver ; Bartolucci, Chiara ; Severi, Stefano ; Shrier, Alvin ; Virag, Laszlo ; Varro, Andras ; Rodriguez, Blanca

Resumen: Human-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

Idioma: Inglés

DOI: 10.7554/eLife.48890

Año: 2019

Publicado en: eLife 8 (2019), e48890 [48 pp.]
ISSN: 2050-084X

Factor impacto JCR: 7.08 (2019)

Categ. JCR: BIOLOGY rank: 5 / 92 = 0.054 (2019) - Q1 - T1

Factor impacto SCIMAGO: 6.079 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1) - Neuroscience (miscellaneous) (Q1) - Medicine (miscellaneous) (Q1) - Immunology and Microbiology (miscellaneous) (Q1)

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Mec.Med.Cont. y Teor.Est. (Dpto. Ingeniería Mecánica)