Paradoxical Onset of Arrhythmic Waves from Depolarized Areas in Cardiac Tissue Due to Curvature-Dependent Instability
Abstract
The generation of abnormal excitations in pathological regions of the heart is a main trigger for lethal cardiac arrhythmias. Such abnormal excitations, also called ectopic activity, often arise from areas with local tissue heterogeneity or damage accompanied by localized depolarization. Finding the conditions that lead to ectopy is important to understand the basic biophysical principles underlying arrhythmia initiation and might further refine clinical procedures. In this study, we are the first to address the question of how geometry of the abnormal region affects the onset of ectopy using a combination of experimental, in silico, and theoretical approaches. We paradoxically find that, for any studied geometry of the depolarized region in optogenetically modified monolayers of cardiac cells, primary ectopic excitation originates at areas of maximal curvature of the boundary, where the stimulating electrotonic currents are minimal. It contradicts the standard critical nucleation theory applied to nonlinear waves in reaction-diffusion systems, where a higher stimulus is expected to produce excitation more easily. Our in silico studies reveal that the nonconventional ectopic activity is caused by an oscillatory instability at t...Continue Reading
References
Spontaneous initiation of premature ventricular complexes and arrhythmias in type 2 long QT syndrome
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