An in silico study of electrophysiological parameters that affect the spiral-wave frequency in mathematical models for cardiac tissue

TL;DR

This study uses detailed mathematical models to analyze how cellular electrophysiological parameters influence spiral wave frequency in cardiac tissue, shedding light on arrhythmia mechanisms and potential fibrotic anchoring effects.

Contribution

It identifies specific cellular and intercellular factors that modulate spiral wave dynamics, including ion-channel conductances and fibroblast coupling, providing new insights into arrhythmia behavior.

Findings

Increased upstroke velocity raises spiral wave frequency.

Shorter action potential duration increases spiral wave frequency.

Fibroblast density influences spiral wave drift and anchoring.

Abstract

Spiral waves of excitation in cardiac tissue are associated with life-threatening cardiac arrhythmias. It is, therefore, important to study the electrophysiological factors that affect the dynamics of these spiral waves. By using an electrophysiologically detailed mathematical model of a myocyte (cardiac cell), we study the effects of cellular parameters, such as membrane-ion-channel conductances, on the properties of the action-potential (AP) of a myocyte. We then investigate how changes in these properties, specifically the upstroke velocity and the AP duration (APD), affect the frequency $\omega$ of a spiral wave in the mathematical model that we use for human-ventricular tissue. We find that an increase (decrease) in this upstroke-velocity or a decrease (increase) in the AP duration increases (decreases) $\omega$. We also study how other intercellular factors, such as the fibroblast-myocyte coupling, diffusive coupling strength, and the effective number of neighboring myocytes, modulate $\omega$. Finally, we demonstrate how a spiral wave can drift to a region with a high density of fibroblasts. Our results provide a natural explanation for the anchoring of spiral waves in highly fibrotic regions in fibrotic hearts.