Abstract

Abnormal electrical activity from the boundaries of ischemic cardiac tissue is recognized as one of the major causes in generation of ischemia-reperfusion arrhythmias. Here we present theoretical analysis of the waves of electrical activity that can rise on the boundary of cardiac cell network upon its recovery from ischaemia-like conditions. The main factors included in our analysis are macroscopic gradients of the cell-to-cell coupling and cell excitability and microscopic heterogeneity of individual cells. The interplay between these factors allows one to explain how spirals form, drift together with the moving boundary, get transiently pinned to local inhomogeneities, and finally penetrate into the bulk of the well-coupled tissue where they reach macroscopic scale. The asymptotic theory of the drift of spiral and scroll waves based on response functions provides explanation of the drifts involved in this mechanism, with the exception of effects due to the discreteness of cardiac tissue. In particular, this asymptotic theory allows an extrapolation of 2D events into 3D, which has shown that cells within the border zone can give rise to 3D analogues of spirals, the scroll waves. When and if such scroll waves escape into a better coupled tissue, they are likely to collapse due to the positive filament tension. However, our simulations have shown that such collapse of newly generated scrolls is not inevitable and that under certain conditions filament tension becomes negative, leading to scroll filaments to expand and multiply leading to a fibrillation-like state within small areas of cardiac tissue.

Highlights

  • Heart is a remarkably reliable machine whose function is to pump the blood as required by the organism

  • This paper focuses on mathematical analysis of arrhythmogenic conditions associated with cardiac tissue recovery from acute ischemia, known as reperfusion arrhythmias

  • What determines the components of the drift velocity, and why the spiral cores can be dragged together with the moving border zone?

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Summary

Introduction

Heart is a remarkably reliable machine whose function is to pump the blood as required by the organism. This paper focuses on mathematical analysis of arrhythmogenic conditions associated with cardiac tissue recovery from acute ischemia, known as reperfusion arrhythmias. Such recovery can be more dangerous ischemia itself and often leads to ventricular fibrillation and sudden cardiac death [1]. Reperfusion can be spontaneous (relief of coronary spasm, dislodging of a thrombus) or externally imposed (antithrombolitic therapy, angioplasty) It can occur on a microscopic scale during ischemia itself as a result in shifts in microcirculation [2]. The exact mechanisms of reperfusion arrhythmias remain poorly understood This is because the inner layers of ischaemic boundary are inaccessible for live visualization on a spatial scale required to distinguish behaviour of individual cells. In order to understand how the abnormal activity spreads from single cells to the bulk of cardiac tissue, we and others had to rely on either in vitro experimental preparations or on computer modeling

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