Spiral-wave dynamics in a mathematical model of human ventricular tissue with myocytes and fibroblasts

PLoS One. 2013 Sep 4;8(9):e72950. doi: 10.1371/journal.pone.0072950. eCollection 2013.

Abstract

Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the electrophysiological properties of cardiac tissue. We present systematic numerical studies of such modulation of electrophysiological properties in mathematical models for (a) single myocyte-fibroblast (MF) units and (b) two-dimensional (2D) arrays of such units; our models build on earlier ones and allow for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP) morphology on parameters such as [Formula: see text], the fibroblast resting-membrane potential, the fibroblast conductance [Formula: see text], and the MF gap-junctional coupling [Formula: see text]. Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various ranges for parameters such as [Formula: see text], and [Formula: see text], and (c) intercellular couplings that can be zero-sided, one-sided, and two-sided connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity [Formula: see text] decreases as a function of [Formula: see text], for zero-sided and one-sided couplings; however, for two-sided coupling, [Formula: see text] decreases initially and then increases as a function of [Formula: see text], and, eventually, we observe that conduction failure occurs for low values of [Formula: see text]. In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling [Formula: see text] or [Formula: see text]. Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models for cardiac tissue, in our MF model both with and without heterogeneities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fibroblasts / cytology*
  • Heart Ventricles / cytology*
  • Humans
  • Models, Theoretical*
  • Muscle Cells / cytology*

Grants and funding

This study was supported by research grants from the Department of Science and Technology (DST), India and the University Grants Commission (UGC), India. Alok Ranjan Nayak was supported by research fellowships from the Council for Scientific and Industrial Research (CSIR), India, Microsoft Research (India), and the Robert Bosch Centre for Cyber Physical Systems (IISc). AV Panfilov also acknowledges the support of the Research-Foundation Flanders (FWO). Computational resources were also provided by the Supercomputer Education and Research Centre (SERC, IISc). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.