Electron-conformational transformations in nanoscopic RyR channels govern both the heart's contraction and beating

We show that a simple biophysically based electron-conformational model of RyR channel is able to explain and describe on equal footing the oscillatory regime of the heart's cell release unit both in sinoatrial node (pacemaker) cells under normal physiological conditions and in ventricular myocytes under Ca$^{2+}$ SR overload.Comment: 6 pages, 3 figure

The concepts Good – Evil in Fiction Linguistic World-Image on the Basis of Modern Arabic and Ukrainian Phraseological Units

У статті здійснено спробу проаналізувати бінарні концепти ДОБРО – ЗЛО в художній мовній картині світу на матеріалі сучасних арабських та українських фразеологізмів та обґрунтувати їх опозиційні взаємо¬зв’язки, які доповнюють знання про особливості семантики фольклорного слова. The scientific paper is attempted to determine the language analysis of the binary concepts GOOD –EVIL in fiction linguistic world-image on the basis of modern Arabic and Ukrainian phraseological units and to base its opposition interconnections with supplement the information relative to the features of the semantics folk word

Anisotropic conduction in the myocardium due to fibrosis: the effect of texture on wave propagation

Cardiac fibrosis occurs in many forms of heart disease. It is well established that the spatial pattern of fibrosis, its texture, substantially affects the onset of arrhythmia. However, in most modelling studies fibrosis is represented by multiple randomly distributed short obstacles that mimic only one possible texture, diffuse fibrosis. An important characteristic feature of other fibrosis textures, such as interstitial and patchy textures, is that fibrotic inclusions have substantial length, which is suggested to have a pronounced effect on wave propagation. In this paper, we study the effect of the elongation of inexcitable inclusions (obstacles) on wave propagation in a 2D model of cardiac tissue described by the TP06 model for human ventricular cells. We study in detail how the elongation of obstacles affects various characteristics of the waves. We quantify the anisotropy induced by the textures, its dependency on the obstacle length and the effects of the texture on the shape of the propagating wave. Because such anisotropy is a result of zig-zag propagation we show, for the first time, quantification of the effects of geometry and source-sink relationship, on the zig-zag nature of the pathway of electrical conduction. We also study the effect of fibrosis in the case of pre-existing anisotropy and introduce a procedure for scaling of the fibrosis texture. We show that fibrosis can decrease or increase the preexisting anisotropy depending on its scaled texture. © 2020, The Author(s).Rochester Academy of Science, RASThis work was supported by Program of RAS Presidium #2, UrFU Competitiveness Enhancement Program (agreement 02.A03.21.0006) and RFBR (No. 18-29-13008). A.P. would like to thank Dr. Rupamanjari Majumder for an advice

New Mathematical Model of Electromechanical Coupling in Rat Cardiomyocytes

The rat is one of the most widely used laboratory animal species. Therefore development of mathematical models aimed to analyze electromechanical coupling in the rat myocardium is a matter of top interest. We have developed a novel model of excitation-contraction coupling in the rat cardiomyocyte. This model combines equations from the Pandit electrophysiological model and Hinch model of calcium handling with equations describing myofilament mechanical activity from the 'Ekaterinburg-Oxford' mathematical model. The model reproduces both fast and slow responses to mechanical interventions in rat myocardium. © 2018 Creative Commons Attribution.Russian Foundation for Basic Research, RFBR: 18-01-00059The work is performed in the frameworks of IIP UrB RAS projects (Nos. AAAA-A18-118020590031-8, АААА-А18-118020590134-6), and supported by RFBR (No. 18-01-00059), by Act 211 Government of the Russian Federation, contract No. 02.A03.21.0006

Detailed Electromechanical Model of Ventricular Wedge

We developed a three-dimensional computational model for describing electro-mechanical behavior of wedge-shaped preparation extracted from the left ventricular wall including excitation wave propagation, high-resolution geometry and fiber orientation. The cardiac tissue is simulated by an incompressible hyperplastic material. We used non-linear partial differential equations describing the deformation of the cardiac tissue, and a detailed 'Ekaterinburg-Oxford' (EO) cellular model of the electrical and mechanical activity of the cardiomyocytes in the tissue. Electro-mechanical coupling in the model accounts for mechano-electric feedbacks both in the cells and in the tissue. Numerical experiments with the model of the wedge preparation formed of initially identical cardiomyocytes revealed that electrical and mechanical interaction between the cells, as well as intracellular mechanoelectric feedbacks caused pronounced nonuniformity of their behavior. © 2018 Creative Commons Attribution.Russian Foundation for Basic Research, RFBR: 18-31-00416Russian Academy of Sciences, RAS: АААА-А18- 118020590030-1This work was carried out within the framework of the IIF UrB RAS themes (Nos. AAAA-A18-118020590031-8) and was supported by RFBR (18-31-00416), the Program of the Presidium RAS #27 (project АААА-А18- 118020590030-1) and Act 211 Government of the Russian Federation, contract № 02.A03.21.0006

In Silico Comparison of Phase Maps Based on Action Potential and Extracellular Potential

In this work, a computer simulation of the reentrant ventricular tachycardia (VT) was used to investigate the peculiar properties of phase maps based on transmembrane potentials (TP) and extracellular potentials (EP). The simulation approach included the bidomain model with full myocardium-torso coupling, a realistic ionic model of the human cardiomyocytes and a personalized geometry of the heart and torso. The phase mapping pipeline includes a signal detrending and the Hilbert transform. It was demonstrated that TP-based phase maps correlated well with the propagation of cardiac excitation. In contrast, EP-based phase mapping provides some aberrations which can complicate electrophysiological interpretation of the phase maps in terms of cardiac activation sequence. It was also shown that a modification of the phase computation algorithm, including the sign inversion of signals and a special transformation of the phase plot, can partially eliminate these aberrations and make EP-based phase maps resemble TP-based maps. © 2018 Creative Commons Attribution.Russian Foundation for Basic Research, RFBR: 18-31-00401The reported study was funded by RFBR according to the research project No. 18-31-00401. Development of computer model with personalized geometry was funded by IIP UrB RAS theme No AAAA-A18-118020590031-8, RF Government Act #211 of March 16, 2013 (agreement 02.A03.21.0006), Program of the Presidium RAS #27 (project AAAA-A18-118020590030-1)

Mechano-Electric Feedbacks in a New Model of the Excitation-Contraction Coupling in Human Cardiomyocytes

The study is aimed to develop a new human cardiomyocyte model, which describes electromechanical coupling and mechano-electric feedbacks. The combined electromechanical model (TP+M) links the TP06 electrophysiological model of the human cardiomyocyte with our earlier developed model of the myocardium mechanical activity and its calcium regulation. In the TP+M model, we tried to maintain principal features of calcium transients and action potentials during the twitches typical for the human cardiomyocytes. The developed TP+M model allows simulating several basic classic phenomena such as load-dependent relaxation and length-dependence of isometric twitches and respective changes in action potential duration. We have also simulated some age-dependent changes in the electrical and mechanical activity in the human cardiomyocytes. © 2018 Creative Commons Attribution.The work was carried out within the framework of the IIP UrB RAS themes (Nos. AAAA-A18-118020590031-8, АААА-А18-118020590134-6) and was supported by Act 211 Government of the Russian Federation, contract № 02.A03.21.0006, and by RFBR (18-01-00059 - single cell modeling; 18-015-00368 – ageing simulation)

The Effects of Mechanical Preload on Transmural Differences in Mechano-Calcium-Electric Feedback in Single Cardiomyocytes: Experiments and Mathematical Models

Transmural differences in ventricular myocardium are maintained by electromechanical coupling and mechano-calcium/mechano-electric feedback. In the present study, we experimentally investigated the influence of preload on the force characteristics of subendocardial (Endo) and subepicardial (Epi) single ventricular cardiomyocytes stretched by up to 20% from slack sarcomere length (SL) and analyzed the results with the help of mathematical modeling. Mathematical models of Endo and Epi cells, which accounted for regional heterogeneity in ionic currents, Ca2+ handling, and myofilament contractile mechanisms, showed that a greater slope of the active tension–length relationship observed experimentally in Endo cardiomyocytes could be explained by greater length-dependent Ca2+ activation in Endo cells compared with Epi ones. The models also predicted that greater length dependence of Ca2+ activation in Endo cells compared to Epi ones underlies, via mechano-calcium-electric feedback, the reduction in the transmural gradient in action potential duration (APD) at a higher preload. However, the models were unable to reproduce the experimental data on a decrease of the transmural gradient in the time to peak contraction between Endo and Epi cells at longer end-diastolic SL. We hypothesize that preload-dependent changes in viscosity should be involved alongside the Frank–Starling effects to regulate the transmural gradient in length-dependent changes in the time course of contraction of Endo and Epi cardiomyocytes. Our experimental data and their analysis based on mathematical modeling give reason to believe that mechano-calcium-electric feedback plays a critical role in the modulation of electrophysiological and contractile properties of myocytes across the ventricular wall. © Copyright © 2020 Khokhlova, Konovalov, Iribe, Solovyova and Katsnelson.AAAA-A18-118020590031-8Russian Foundation for Basic Research, RFBR: 18-01-00059Russian Science Foundation, RSF: 18-74-10059Funding. Wet experiments were supported by the Russian Science Foundation (#18-74-10059). The development of mouse ventricular cardiomyocyte model was supported by the Russian Foundation for Basic Research (#18-01-00059), IIF UrB RAS theme (AAAA-A18-118020590031-8), and by RF Government Act #211 of March 16, 2013 (agreement 02.A03.21.0006)

Comparison of Depolarization and Depolarization in Mathematical Models of the Left Ventricle and the Longitudinal Ventricular Slice

Myocardial slices are widely used for cardiac electrophysiology research but correspondence of electrophysiological properties between the cardiac slices and the whole heart has not been studied in details. The aim of this study is to investigate the differences in electrophysiological properties between the left ventricle and the longitudinal ventricular slice passing through the apex using mathematical models. ECG signals and the time of activation and repolarization, repolarization dispersion and dispersion of action potential duration were compared. We have shown that the electrophysiological processes in the ventricle and the longitudinal ventricular slice are quite similar, so we believe that cardiac slices can be used to evaluate global electrophysiological properties of the ventricles. The local differences obtained can be explained by differences in geometry and fiber orientation locally affecting depolarization and repolarization in the myocardium. © 2018 Creative Commons Attribution.Russian Foundation for Basic Research, RFBR: 16-31-60015, 18-31-00401This work was supported by IIF UrB RAS theme #AAAA-A18-118020590031-8, RFE Government Act #211 of March 16, 2013, the Program of the Presidium RAS #27 and RFBR (#16-31-60015, 18-31-00401)

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. © 2020 The Author(s).Russian Foundation for Basic Research, RFBR: 18‑01‑00059The work was carried out within the framework of the IIP UrB RAS themes (Nos. AAAA‑A18‑118020590031‑8, AAAA‑A18‑118020590134‑6) and was supported by RFBR (18‑01‑00059) and by Act 211 Government of the Russian Federation, contract No. 02.A03.21.0006