Virtual cardiac monolayers for electrical wave propagation

Nina Kudryashova,Valeriya Tsvelaya,Konstantin Agladze,Alexander Panfilov

doi:10.1038/s41598-017-07653-3

Nina Kudryashova, Valeriya Tsvelaya + Show 2 more

Open Access

https://doi.org/10.1038/s41598-017-07653-3

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Abstract

The complex structure of cardiac tissue is considered to be one of the main determinants of an arrhythmogenic substrate. This study is aimed at developing the first mathematical model to describe the formation of cardiac tissue, using a joint in silico–in vitro approach. First, we performed experiments under various conditions to carefully characterise the morphology of cardiac tissue in a culture of neonatal rat ventricular cells. We considered two cell types, namely, cardiomyocytes and fibroblasts. Next, we proposed a mathematical model, based on the Glazier-Graner-Hogeweg model, which is widely used in tissue growth studies. The resultant tissue morphology was coupled to the detailed electrophysiological Korhonen-Majumder model for neonatal rat ventricular cardiomyocytes, in order to study wave propagation. The simulated waves had the same anisotropy ratio and wavefront complexity as those in the experiment. Thus, we conclude that our approach allows us to reproduce the morphological and physiological properties of cardiac tissue.

Highlights

The complex structure of cardiac tissue is considered to be one of the main determinants of an arrhythmogenic substrate
Cell cultures grown on such an artificial extracellular matrix (ECM), which imitates the ECM of the heart, effectively reproduce the anisotropy of cardiac tissue[24]
We developed a powerful tool to study the relation between morphology and electrical wave propagation in cardiac monolayers

Summary

Introduction

The complex structure of cardiac tissue is considered to be one of the main determinants of an arrhythmogenic substrate. In addition to FBs, there exist structural extracellular proteins (e.g. collagens), which form the extracellular matrix (ECM) and affect the CM phenotype[2] The latter is essential for proper mechanical functioning of the heart[3] and for uninterrupted electrical signal propagation[4]. The interaction between CMs, FBs, and extracellular proteins results in the formation of a complex tissue texture Such a texture changes substantially during most cardiac diseases, via a process called remodelling. The most logical way to approach this problem, is to represent knowledge about such processes in terms of a mathematical model of structural tissue formation This model should be based on extensive experimental data, which can be used to explain the observed textures and to develop methods to control remodelling. We develop this model for a classical experimental model system–cardiac www.nature.com/scientificreports/

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