Key result
In a mathematical model of human ventricular tissue, myocyte-fibroblast coupling alters action potential morphology and conduction velocity, and can control the rotation speed and stability of spiral waves.
In a mathematical model of human ventricular tissue, myocyte-fibroblast coupling significantly alters action potential morphology, conduction velocity, and spiral wave dynamics, providing mechanistic insights into arrhythmogenesis.
Hypothesis-generating for fibroblast modulation of reentry; leaves open translation to human arrhythmia therapies.
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.
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Nayak et al. (2013) studied Cardiac electrophysiology. Myocyte-fibroblast coupling parameters vs. Uncoupled myocytes was evaluated on Action potential morphology and conduction velocity. In a mathematical model of human ventricular tissue, myocyte-fibroblast coupling alters action potential morphology and conduction velocity, and can control the rotation speed and stability of spiral waves.
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