Please use this identifier to cite or link to this item: http://hdl.handle.net/10995/75629
Title: Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fraction of nonconducting cells
Authors: Kudryashova, N.
Nizamieva, A.
Tsvelaya, V.
Panfilov, A. V.
Agladze, K. I.
Issue Date: 2019
Publisher: Public Library of Science
Citation: Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fraction of nonconducting cells / N. Kudryashova, A. Nizamieva, V. Tsvelaya et al. // PLoS Computational Biology. — 2019. — Vol. 15. — Iss. 3. — e1006597.
Abstract: Cardiac fibrosis occurs in many forms of heart disease and is considered to be one of the main arrhythmogenic factors. Regions with a high density of fibroblasts are likely to cause blocks of wave propagation that give rise to dangerous cardiac arrhythmias. Therefore, studies of the wave propagation through these regions are very important, yet the precise mechanisms leading to arrhythmia formation in fibrotic cardiac tissue remain poorly understood. Particularly, it is not clear how wave propagation is organized at the cellular level, as experiments show that the regions with a high percentage of fibroblasts (65-75%) are still conducting electrical signals, whereas geometric analysis of randomly distributed conducting and non-conducting cells predicts connectivity loss at 40% at the most (percolation threshold). To address this question, we used a joint in vitro-in silico approach, which combined experiments in neonatal rat cardiac monolayers with morphological and electrophysiological computer simulations. We have shown that the main reason for sustainable wave propagation in highly fibrotic samples is the formation of a branching network of cardiomyocytes. We have successfully reproduced the morphology of conductive pathways in computer modelling, assuming that cardiomyocytes align their cytoskeletons to fuse into cardiac syncytium. The electrophysiological properties of the monolayers, such as conduction velocity, conduction blocks and wave fractionation, were reproduced as well. In a virtual cardiac tissue, we have also examined the wave propagation at the subcellular level, detected wavebreaks formation and its relation to the structure of fibrosis and, thus, analysed the processes leading to the onset of arrhythmias. © 2019 Kudryashova et al.
Keywords: ANIMAL
BIOLOGICAL MODEL
COMPUTER SIMULATION
HEART
HEART ARRHYTHMIA
HEART MUSCLE CONDUCTION SYSTEM
NEWBORN
PATHOPHYSIOLOGY
PHYSIOLOGY
RAT
ANIMALS
ANIMALS, NEWBORN
ARRHYTHMIAS, CARDIAC
COMPUTER SIMULATION
HEART
HEART CONDUCTION SYSTEM
MODELS, CARDIOVASCULAR
RATS
URI: http://hdl.handle.net/10995/75629
Access: info:eu-repo/semantics/openAccess
SCOPUS ID: 85064142612
WOS ID: 000463877900012
PURE ID: 9309926
ISSN: 1553-734X
DOI: 10.1371/journal.pcbi.1006597
Appears in Collections:Научные публикации, проиндексированные в SCOPUS и WoS CC

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