Competing Mechanisms of Stress-Assisted Diffusivity and Stretch-Activated Currents in Cardiac Electromechanics.

Alessandro Loppini,Ricardo Ruiz-Baier,Alessio Gizzi,Christian Cherubini,Simonetta Filippi,Flavio H Fenton

doi:10.3389/fphys.2018.01714

Abstract

We numerically investigate the role of mechanical stress in modifying the conductivity properties of cardiac tissue, and also assess the impact of these effects in the solutions generated by computational models for cardiac electromechanics. We follow the recent theoretical framework from Cherubini et al. (2017), proposed in the context of general reaction-diffusion-mechanics systems emerging from multiphysics continuum mechanics and finite elasticity. In the present study, the adapted models are compared against preliminary experimental data of pig right ventricle fluorescence optical mapping. These data contribute to the characterization of the observed inhomogeneity and anisotropy properties that result from mechanical deformation. Our novel approach simultaneously incorporates two mechanisms for mechano-electric feedback (MEF): stretch-activated currents (SAC) and stress-assisted diffusion (SAD); and we also identify their influence into the nonlinear spatiotemporal dynamics. It is found that (i) only specific combinations of the two MEF effects allow proper conduction velocity measurement; (ii) expected heterogeneities and anisotropies are obtained via the novel stress-assisted diffusion mechanisms; (iii) spiral wave meandering and drifting is highly mediated by the applied mechanical loading. We provide an analysis of the intrinsic structure of the nonlinear coupling mechanisms using computational tests conducted with finite element methods. In particular, we compare static and dynamic deformation regimes in the onset of cardiac arrhythmias and address other potential biomedical applications.

Highlights

Cardiac tissue is a complex multiscale medium constituted by highly interconnected units, cardiomyocytes, that conform a so-called syncitium with unique structural and functional properties (Pullan et al, 2005)
Focusing on the organ scale, the clinical relevance of mechano-electric feedback (MEF) in patients with heart diseases remains an open issue (Orini et al, 2017), and how MEF mechanisms translate into ECGs (Meijborg et al, 2017) and what is the specific role of mechanics during cardiac arrhythmias (Christoph et al, 2018)
We have advanced a minimal model for the electromechanics of cardiac tissue, where the mechano-electrical feedback is incorporated through two competing mechanisms: the stretchactivated currents commonly found in the literature, and the stress-assisted diffusion recently proposed by Cherubini et al (2017)

Summary

Introduction

Cardiac tissue is a complex multiscale medium constituted by highly interconnected units, cardiomyocytes, that conform a so-called syncitium with unique structural and functional properties (Pullan et al, 2005). Cardiomyocytes are excitable and deformable muscular cells that present themselves an additional multiscale architecture in which plasma membrane proteins and Competing Mechanisms in Cardiac Electromechanics intracellular organelles all depend on the current mechanical state of the tissue (Salamhe and Dhein, 2013; Schönleitner et al, 2017). Dedicated proteic structures, such as ion channels or gap junctions, rule the passage of charged particles throughout the cell as well as between different cells and they are usually described mathematically through multiple reaction-diffusion (RD) systems (Cabo, 2014; Dhein et al, 2014; Kleber and Saffitz, 2014). Focusing on the organ scale, the clinical relevance of MEF in patients with heart diseases remains an open issue (Orini et al, 2017), and how MEF mechanisms translate into ECGs (Meijborg et al, 2017) and what is the specific role of mechanics during cardiac arrhythmias (Christoph et al, 2018)

Methods

Results

Conclusion