Human atrial fibrillation: insights from computational electrophysiological models

Abstract

Computational electrophysiology has proven useful to investigate the mechanisms of cardiac arrhythmias at various spatial scales, from isolated myocytes to the whole heart. This article reviews how mathematical modeling has aided our understanding of human atrial myocyte electrophysiology to study the contribution of structural and electrical remodeling to human atrial fibrillation. Potential new avenues of investigation and model development are suggested.

Figure 1

A) Schematic representation of the electrophysiological and Ca²⁺ handling processes formulated in human atrial myocyte models. Alterations associated to AF are highlighted. Simulated APs (B and C) and Ca²⁺ transients (D and E) at various pacing rates in sinus rhythm and cAF respectively [Modified from (Grandi et al. 2011)]. Sinus rhythm (black) and cAF (blue) APs and Ca²⁺ transients at 1-Hz pacing frequency are shown in insets for comparison. AC: adenylate cyclase, ATP: adenosine triphosphate, β-AR: β-adrenergic receptor, CaM: calmodulin, cAMP: cyclic adenosine monophosphate, G: guanine nucleotide-binding protein, PKA: protein kinase A, PLB: phospholamban, PLM: phospholemman, PMCA: plasmalemmal Ca²⁺ pump, PPase: protein phosphatase.

Figure 2

Schematic representation of adrenergic (blue), CaMKII (red) and oxidative (green) signaling (all enhanced in cAF) and effects on targets. CFTR: cystic fibrosis transmembrane conductance regulator.

Figure 3

Heterogeneous model of the human atria [From (Aslanidi et al. 2011) with permission]. A) AP profiles in the right atrium, left atrium, pectinate muscle and crista terminalis cells. B) Spontaneous APs in the SAN. C) 3-D anatomical model of the human atria showing the main conductive bundles.