000170434 001__ 170434
000170434 005__ 20260422084206.0
000170434 0247_ $$2doi$$a10.1371/journal.pcbi.1013740
000170434 0248_ $$2sideral$$a148900
000170434 037__ $$aART-2026-148900
000170434 041__ $$aeng
000170434 100__ $$aRosales, Ricardo M.
000170434 245__ $$aIn silico assessment of arrhythmic risk following the implantation of engineered heart tissues in porcine hearts with varying infarct locations
000170434 260__ $$c2026
000170434 5060_ $$aAccess copy available to the general public$$fUnrestricted
000170434 5203_ $$aEngineered heart tissues (EHTs) have shown promise in partially restoring ejection fraction after myocardial infarction (MI); however, their potential to introduce electrophysiological heterogeneities and promote arrhythmias remains underexplored. This study assessed the arrhythmogenic risk following immature EHT engraftment in infarcted ventricles using computational simulations that replicate preclinical protocols. EHT computational models were developed and integrated into nine validated porcine-specific biventricular models from pigs with left circumflex (LCx, n = 4) or left anterior descending (LAD, n = 5) MIs. Ventricular tachycardia (VT) susceptibility was evaluated using an S1–S2 stimulation protocol across varying pacing sites and coupling intervals, accounting for infarct characteristics, implantation site, conductivity, and the ventricular conduction system (CS). VT burden was quantified with a 0–1 inducibility score (IS). In silico reentrant activity qualitatively reproduced the arrhythmic patterns observed experimentally in porcine MI models. VT vulnerability was greater in LAD than in LCx infarcts, consistent with a larger infarct size. Inclusion of the CS modified VT burden by providing conduction shortcuts that either facilitated or suppressed reentry. Remuscularization directly on the MI region (IS = 0.49) heightened VT inducibility in dense, transmural scars (IS = 0.16), whereas lateral EHT implantation (IS = 0.35) reduced this risk with respect to direct implantation. In non-transmural scars, VT inducibility varied with the implantation site. Matching EHT conductivity to host myocardium lowered or contained arrhythmogenicity (LCx-IS: from 0.5 to 0.25; LAD-IS: stable at 0.57). These results highlight the latent arrhythmic risk of EHT-mediated remuscularization after MI, identifying infarct substrate, EHT conductivity, and implantation site as critical determinants, and emphasize the importance of incorporating the CS for accurate risk assessment
000170434 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000170434 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000170434 700__ $$aRíos-Muñoz, Gonzalo R.
000170434 700__ $$aSánchez de la Nava, Ana María
000170434 700__ $$aFernández-Santos, María Eugenia
000170434 700__ $$aBermejo, Javier
000170434 700__ $$0(orcid)0000-0001-8741-6452$$aDoblaré, Manuel$$uUniversidad de Zaragoza
000170434 700__ $$0(orcid)0000-0003-3183-4107$$aMincholé, Ana$$uUniversidad de Zaragoza
000170434 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, Esther$$uUniversidad de Zaragoza
000170434 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000170434 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000170434 773__ $$g22, 4 (2026), e1013740 [32 pp.]$$pPLoS Comput. Biol.$$tPLOS COMPUTATIONAL BIOLOGY$$x1553-734X
000170434 8564_ $$s3658960$$uhttps://zaguan.unizar.es/record/170434/files/texto_completo.pdf$$yVersión publicada
000170434 8564_ $$s2802676$$uhttps://zaguan.unizar.es/record/170434/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000170434 909CO $$ooai:zaguan.unizar.es:170434$$particulos$$pdriver
000170434 951__ $$a2026-04-22-08:40:12
000170434 980__ $$aARTICLE