Biology subjects

Panfilov, A.

Publications and source records attributed to Panfilov, A..

4 recordsLinked to original sources

bioRxiv2021

Rotational Activity Around an Obstacle in 2D Cardiac Tissue in Presence of Cellular Heterogeneity

Waves of electrical excitation rotating around an obstacle is one of the important mechanisms of dangerous cardiac arrhythmias occurring in the heart damaged by post-infarction scar. Such a scar also has a border zone around it, which has electrophysiological properties different from the rest of normal myocardial tissue. Spatial patterns of wave rotation in the presence of such tissue heterogeneity are poorly studied. In this paper we perform a comprehensive numerical study of various regimes of rotation of a wave in a plane layer of the ventricular tissue around an obstacle surrounded by a gray zone. We use a TP06 cellular ionic model which reproduces the electrophysiological properties of cardiomyocytes in the left ventricle of human heart. We vary the extent of obstacle and gray zone and study the pattern of wave rotation and its period. We observed different regimes of wave rotation that can be subdivided into several classes: (1) functional rotation and (2) scar rotation regimes, which were identified in the previous studies, and new (3) gray zone rotation regime: where the wave instead of rotation around the obstacle, rotates around the gray zone (an area of tissue heterogeneity) itself. For each class, the period of rotation is determined by different factors, which we discuss and quantify. We also found that due to regional pathological remodeling of myocardial tissue, we can obtain additional regimes associated with dynamical instabilities of two types which may affect or not affect the period of rotation.

physiology↗

bioRxiv2019

Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model

Experiments on animal hearts (rat, rabbit, guinea pig, etc.) have demonstrated that mechano-calcium feedback (MCF) and mechano-electric feedback (MEF) are very important for myocardial self-regulation because they adjust the cardiomyocyte contractile function to various mechanical loads and to mechanical interactions between heterogeneous myocardial segments in the ventricle walls. In in vitro experiments on these animals, MCF and MEF manifested themselves in several basic classical phenomena (e.g. load dependence, length dependence of isometric twitches, etc.), and in the respective responses of calcium transients and action potentials. However, it is extremely difficult to study simultaneously the electrical, calcium, and mechanical activities of the human heart muscle in vitro. Mathematical modeling is a useful tool for exploring these phenomena. We have developed a novel model to describe electromechanical coupling and mechano-electric feedbacks in the human cardiomyocyte. It combines the ten Tusscher - Panfilov electrophysiological model of the human cardiomyocyte with our module of myocardium mechanical activity taken from the Ekaterinburg - Oxford model and adjusted to human data. Using it, we simulated isometric and afterloaded twitches and effects of MCF and MEF on excitation-contraction coupling. MCF and MEF were found to affect significantly the duration of the calcium transient and action potential in the human cardiomyocyte model in response to both smaller afterloads as compared to bigger ones and various mechanical interventions applied during isometric and afterloaded twitches.

biophysics↗

bioRxiv2019

Directed networks as a novel way to describe and analyze cardiac excitation: Directed Graph mapping

Networks provide a powerful methodology with applications in a variety of biological, technological and social systems such as analysis of brain data, social networks, internet search engine algorithms, etc. To date, directed networks have not yet been applied to characterize the excitation of the human heart. In clinical practice, cardiac excitation is recorded by multiple discrete electrodes. During (normal) sinus rhythm or during cardiac arrhythmias, successive excitation connects neighboring electrodes, resulting in their own unique directed network. This in theory makes it a perfect fit for directed network analysis. In this study, we applied directed networks to the heart in order to describe and characterize cardiac arrhythmias. Proofof-principle was established using in-silico and clinical data. We demonstrated that tools used in network theory analysis allow to determine the mechanism and location of certain cardiac arrhythmias. We show that the robustness of this approach can potentially exceed the existing state-of-the art methodology used in clinics. Furthermore, implementation of these techniques in daily practice can improve accuracy and speed of cardiac arrhythmia analysis. It may also provide novel insights in arrhythmias that are still incompletely understood.

physiology↗

bioRxiv2018

Optogenetics enables real-time spatiotemporal control over spiral wave dynamics in an excitable cardiac system

Propagation of non-linear waves is key to the functioning of diverse biological systems. Such waves can organize into spirals, rotating around a core, whose properties determine the overall wave dynamics. Theoretically, manipulation of a spiral wave core should lead to full spatiotemporal control over its dynamics. However, this theory lacks supportive evidence (even at a conceptual level), making it thus a long-standing hypothesis. Here, we propose a new phenomenological concept that involves artificially dragging spiral waves by their cores, to prove the afore-mentioned hypothesis in silico, with subsequent in vitro validation in optogenetically-modified monolayers of rat atrial cardiomyocytes. We thereby connect previously established, but unrelated concepts of spiral wave attraction, anchoring and unpinning to demonstrate that core manipulation, through controlled displacement of heterogeneities in excitable media, allows forced movement of spiral waves along pre-defined trajectories. Consequently, we impose real-time spatiotemporal control over spiral wave dynamics in a biological system.

bioinformatics↗