In SilicoEvaluation of Cell Therapy in Acute versus Chronic Infarction: Role of Automaticity, Heterogeneity and Purkinje in Human

Author:

Riebel Leto LuanaORCID,Wang Zhinuo JennyORCID,Martinez-Navarro HectorORCID,Trovato Cristian,Camps JuliaORCID,Berg Lucas Arantes,Zhou XinORCID,Doste Ruben,Oliveira Rafael Sachetto,Weber dos Santos Rodrigo,Biasetti Jacopo,Rodriguez Blanca

Abstract

AbstractHuman-based modelling and simulation offer an ideal testbed for novel medical therapies to guide experimental and clinical studies. Myocardial infarction (MI) is a common cause of heart failure and mortality, for which novel therapies are urgently needed. Although cell therapy offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns, where underlying complex spatio-temporal dynamics cannot be investigated experimentally. After demonstrating credibility of the modelling and simulation framework, we investigate cell therapy in acute versus chronic MI, and the role of cell heterogeneity, scar size and the Purkinje system.Simulations agreed with experimental and clinical recordings from ionic to ECG dynamics in acute and chronic infarction. Following cell delivery, spontaneous beats were facilitated by heterogeneity in cell populations, chronic MI due to tissue depolarisation, and slow sinus rhythm. Subsequent re-entrant arrhythmias occurred, in some instances with Purkinje involvement, and their susceptibility was enhanced by impaired Purkinje-myocardium coupling, large scars, and acute infarction.We conclude that homogeneity in injected cell populations minimises their spontaneous beating, which is enhanced by chronic MI, whereas a healthy Purkinje-myocardium coupling is key to prevent subsequent re-entrant arrhythmias, particularly for large scars.

Publisher

Cold Spring Harbor Laboratory

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