Biomathematics / Computational Biology Colloquium
In silico–in vitro approach to study the mechanisms of cardiac arrhythmias
Speaker: Alexander V. Panfilov, Department of Physics and Astronomy, Gent University, Belgium
Location: Warren Weaver Hall 1314
Date: Tuesday, May 8, 2018, 12:30 p.m.
I will report on results of our two recent studies both of which combine in-silico and experimental approaches.
Study one is aimed at developing the first mathematical model to describe the formation of cardiac tissue, using a joint in silico–in vitro approach. We performed experiments under various conditions to carefully characterise the morphology of cardiac tissue in a culture of neonatal rat ventricular cells. We considered two cell types, namely, cardiomyocytes and fibroblasts. Next, we proposed a mathematical model, based on the Glazier-Graner-Hogeweg model, which is widely used in tissue growth studies. The resultant tissue morphology was coupled to the detailed electrophysiological Korhonen-Majumder model for neonatal rat ventricular cardiomyocytes, in order to study wave propagation. Using this model we studied the main factors underlying the formation of electrical anisotropy of cardiac tissue and also studied the conditions of block of wave propagation during fibrosis, which is one of the most important arrhythmogenic conditions.
In the second study we address the question of how geometry of the abnormal region affects the onset of ectopy using a combination of optogenetics, experimental electrophysiology, in-silico modelling 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 from 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 non-conventional ectopic activity is caused by an oscillatory instability at the boundary of the damaged region, the occurrence of which depends on the curvature of that boundary. The onset of this instability is confirmed using the Schroedinger equation methodology proposed by Rinzel and Keener [SIAM J. Appl. Math 43(4), 1983]. Overall, we show distinctively novel insight into how the geometry of a heterogeneous cardiac region determines ectopic activity, which can be used in the future to predict the conditions that can trigger cardiac arrhythmias.
For other directions of our research please see: http://scholar.google.com/citations?hl=en&user=lnUL8x0AAAAJ