Dynamical mechanism for generation of arrhythmogenic early afterdepolarizations in cardiac myocytes: insights from in silico electrophysiological models

Barrio, R. (Universidad de Zaragoza) ; Martínez, M. A. (Universidad de Zaragoza) ; Serrano, S. (Universidad de Zaragoza) ; Pueyo, E. (Universidad de Zaragoza)

Resumen: We analyze the dynamical mechanisms underlying the formation of arrhythmogenic early afterdepolarizations (EADs) in two mathematical models of cardiac cellular electrophysiology: the Sato et al. biophysically detailed model of a rabbit ventricular myocyte of dimension 27 and a reduced version of the Luo-Rudy mammalian myocyte model of dimension 3. Based on a comparison of the two models, with detailed bifurcation analysis using spike-counting techniques and continuation methods in the simple model and numerical explorations in the complex model, we locate the point where the first EAD originates in an unstable branch of periodic orbits. These results serve as a basis to propose a conjectured scheme involving a hysteresis mechanism with the creation of alternans and EADs in the unstable branch. This theoretical scheme fits well with electrophysiological experimental data on EAD generation and hysteresis phenomena. Our findings open the door to the development of novel methods for pro-arrhythmia risk prediction related to EAD generation without actual induction of EADs.

Idioma: Inglés

DOI: 10.1103/PhysRevE.106.024402

Año: 2022

Publicado en: Physical Review E 106, 2 (2022), 024402 [8 pp.]
ISSN: 2470-0045

Factor impacto JCR: 2.4 (2022)

Categ. JCR: PHYSICS, MATHEMATICAL rank: 11 / 56 = 0.196 (2022) - Q1 - T1
Categ. JCR: PHYSICS, FLUIDS & PLASMAS rank: 17 / 34 = 0.5 (2022) - Q2 - T2

Factor impacto CITESCORE: 4.6 - Mathematics (Q1) - Physics and Astronomy (Q2)

Factor impacto SCIMAGO: 0.819 - Condensed Matter Physics (Q1) - Statistics and Probability (Q2) - Statistical and Nonlinear Physics (Q2)

Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2021-122961NB-I00
Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/E24-17R
Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/T39-20R-BSICoS group
Financiación: info:eu-repo/grantAgreement/ES/DGA/LMP124-18
Financiación: info:eu-repo/grantAgreement/ES/DGA/LMP94_21
Financiación: info: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
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PGC2018-096026-B-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN-FEDER/PID2019-105674RB-I00

Tipo y forma: Article (Published version)

Área (Departamento): Área Matemática Aplicada (Dpto. Matemática Aplicada)
Área (Departamento): Área Teoría Señal y Comunicac. (Dpto. Ingeniería Electrón.Com.)