Papers by Leonid Katsnelson
Unsupervised deep network for image texture transformation: Improving the quality of cross-correlation analysis and mechanical vortex visualisation during cardiac fibrillation
Heliyon
Mechanical Manifestation of Complete and Incomplete Spiral Wave Break Up
2022 IEEE International Multi-Conference on Engineering, Computer and Information Sciences (SIBIRCON), Nov 11, 2022
Frontiers in Physiology
Background: Populations of in silico electrophysiological models of human cardiomyocytes represen... more Background: Populations of in silico electrophysiological models of human cardiomyocytes represent natural variability in cell activity and are thoroughly calibrated and validated using experimental data from the human heart. The models have been shown to predict the effects of drugs and their pro-arrhythmic risks. However, excitation and contraction are known to be tightly coupled in the myocardium, with mechanical loads and stretching affecting both mechanics and excitation through mechanisms of mechano-calcium-electrical feedback. However, these couplings are not currently a focus of populations of cell models.Aim: We investigated the role of cardiomyocyte mechanical activity under different mechanical conditions in the generation, calibration, and validation of a population of electro-mechanical models of human cardiomyocytes.Methods: To generate a population, we assumed 11 input parameters of ionic currents and calcium dynamics in our recently developed TP + M model as varying ...
Effects of Subchronic Lead Intoxication on the Myocardium Contractility of Rats
Toxicological Review, 2018
While it is known that chronic lead intoxication in humans induces arterial hypertension and thus... more While it is known that chronic lead intoxication in humans induces arterial hypertension and thus can lead to some secondary disturbances of heart function, possible effects of this intoxication on myocardium contractility has never been proved. In our experiments outbred male rats were repeatedly injected IP with sub-lethal doses of lead acetate 3 times a week during 5 weeks. They developed an explicit even if moderate lead intoxication characterized by typical hematological and some other features. Next day after the last injection the heart of each animal was excised, and trabecules and papillary muscles from right ventricle were used for modeling in vitro isometric regimes of contraction-relaxation cycle. Several well-established parameters of this model proved to be changed as compared with preparations taken from hearts of healthy control rats. Against the background of in vivocalcium treatment both systemic and cardiotoxic effects of lead were somewhat attenuated. For the fir...
Biophysics, 2012
The electrical and mechanical activity of heart ventricle cardiomyocytes is known to vary depend ... more The electrical and mechanical activity of heart ventricle cardiomyocytes is known to vary depend ing on the spatial location of cells in the wall, in particular, transmurally from the sub endocardial layer to the sub epicardial one. To investigate intracellular mechanisms of the functional heterogeneity of cardiomyo cytes we developed mathematical models of the electromechanical coupling in cardiomyocytes from different transmural layers across the left ventricle (LV) wall of guinea pig. It is shown that the mechanisms of both direct linkages and feedback in the electromechanical coupling contribute to differences in both the shape and duration of action potential, and speed characteristics of contraction between isolated cardiac myocytes from the sub endocardial and sub epicardial layers.
Journal of Molecular and Cellular Cardiology, 2018
Mechanical properties of cardiomyocytes from different transmural regions are heterogeneous in th... more Mechanical properties of cardiomyocytes from different transmural regions are heterogeneous in the left ventricular wall. The cardiomyocyte mechanical environment affects this heterogeneity because of mechano-electric feedback mechanisms. In the present study, we investigated the effects of load upon transmural differences in contraction of subendocardial (ENDO) and subepicardial (EPI) single cells isolated from the murine left ventricle. Various loads were applied to the cells using carbon fiber techniques for single myocytes. To simulate experimentally obtained results and to predict mechanisms underlying the cellular response to change in load, our mathematical models of the ENDO and EPI cells were used. Extent of the transmural gradient in the time course of contractions was independent of the loading conditions where unloaded and heavy loaded (isometric) contractions were examined, but the regional gradient of the relaxation time characteristics tended to decrease when the load decreased. Under auxotonic contractions, time to peak contraction (Tmax) was significantly longer in ENDO cells than in EPI cells at low preload. An increase in preload (axial stretch) prolonged Tmax in both cell types; however, the prolongation was greater in EPI cells, resulting in a decrease in transmural gradient in Tmax at high preload. The [Ca 2+ ]i transient decay time constant was consistent with the greater preload dependency in Tmax of EPI cells. Our modified mathematical models reproduced experimental results, suggesting that differences in cooperativity of cross bridges and calcium troponin C complex interactions between the ENDO and EPI cardiomyocytes may contribute to
Frontiers in Physiology
Although fibroblasts are about 5–10 times smaller than cardiomyocytes, their number in the ventri... more Although fibroblasts are about 5–10 times smaller than cardiomyocytes, their number in the ventricle is about twice that of cardiomyocytes. The high density of fibroblasts in myocardial tissue leads to a noticeable effect of their electromechanical interaction with cardiomyocytes on the electrical and mechanical functions of the latter. Our work focuses on the analysis of the mechanisms of spontaneous electrical and mechanical activity of the fibroblast-coupled cardiomyocyte during its calcium overload, which occurs in a variety of pathologies, including acute ischemia. For this study, we developed a mathematical model of the electromechanical interaction between cardiomyocyte and fibroblasts and used it to simulate the impact of overloading cardiomyocytes. In contrast to modeling only the electrical interaction between cardiomyocyte and fibroblasts, the following new features emerge in simulations with the model that accounts for both electrical and mechanical coupling and mechano-...
Integrative Mathematical Model of Electrical, Metabolic and Mechanical Processes in Human Cardiomyocytes
Journal of Evolutionary Biochemistry and Physiology
Arrhythmogenesis in calcium-overloaded human cardiomyocytes in isolation and within cardiac tissue. Simulation study
2021 IEEE Ural-Siberian Conference on Computational Technologies in Cognitive Science, Genomics and Biomedicine (CSGB), 2021
Calcium overload of cardiomyocytes is fraught with rhythm disturbances. We are being involving ma... more Calcium overload of cardiomyocytes is fraught with rhythm disturbances. We are being involving mathematical modeling to study this phenomenon. Here we implemented our recently developed mathematical model of the human ventricular cardiomyocyte electromechanical activity 'TP+M' and one-dimensional virtual myocardial strand in which both electrical and mechanical interactions between the cells are accounted for. Each cell in the strand is represented by the TP+M model. Mechano-electric feedback loops in the model are provided by the intracellular mechanisms of cooperativity between regulatory and contractile proteins. Numerical experiments in the onedimensional strand revealed that mechanical interaction between the cells provoked rhythm disturbances in the multicellular myocardium locally overloaded with calcium. Subcellular excitation-contraction coupling including mechano-electric feedback mechanisms underlay vulnerability to the arrhythmia. Electrotonic interaction of the calciumoverloaded myocytes with fibroblasts revealed clear albeit moderate antiarrhythmic effects both in the single cell model and in the one-dimensional strand.
Work Performance in Failing Myocardium Assessed in a Mathematical Model of the Human Ventricular Myocyte Electromechanical Coupling
2021 IEEE Ural-Siberian Conference on Computational Technologies in Cognitive Science, Genomics and Biomedicine (CSGB), 2021
Ventricular contraction cycle is characterized by specific scenario of the mechanical loading, wh... more Ventricular contraction cycle is characterized by specific scenario of the mechanical loading, which in experiments with the heart muscles/myocytes is mimicked by a work-loop mode of the myocardium twitch. We used recently developed electromechanical model of human ventricular cardiomyocyte to simulate its action potential generation, intracellular calcium dynamics and mechanical activity during work-loop twitches under different afterloads in normal and failing myocardium. The model reproduces well the changes in the force development and shortening observed in experiment with normal and failing human left ventricular wall preparations. The model was also used to predict and explain concomitant changes in action potential generation and calcium transient time course. We also calculated the useful work performed by the virtual muscle in normal and failing myocardium revealing that decrease in sarcoplasmic reticulum calcium content during heart failure may underlie the decrease in myocardial work.
ЗДОРОВЬЕ НАСЕЛЕНИЯ И СРЕДА ОБИТАНИЯ - ЗНиСО / PUBLIC HEALTH AND LIFE ENVIRONMENT, 2021
Background: As by-products of copper smelting, lead and cadmium pollute both workplace air at met... more Background: As by-products of copper smelting, lead and cadmium pollute both workplace air at metallurgical plants and adjacent territories. Their increased levels in the human body pose a higher risk of cardiovascular diseases. The objective of our study was evaluate changes in the rat myocardium contractile function following moderate subchronic exposure to soluble lead and/or cadmium salts and its attenuation by means of a complex of bioprotectors. Materials and methods: The subchronic exposure of rats was modelled by intraperitoneal injections of 3-H2O lead acetate and/or 2.5-H2O cadmium chloride in single doses, 6.01 mg of Pb and 0.377 mg of Cd per kg of body weight, respectively, 3 times a week during 6 weeks. The myosin heavy chains isoform ratio was estimated by gel electrophoresis. Biomechanical measurements were performed on isolated multicellular preparations of the myocardium (trabeculae and papillary muscles) from the right ventricle. Results: The subchronic lead exposu...
Mathematical Model of Electrotonic Interaction Between Mechanically Active Cardiomyocyte and Fibroblasts
2019 Ural Symposium on Biomedical Engineering, Radioelectronics and Information Technology (USBEREIT)
Cardiac fibroblasts are widely represented in mammalian cardiac tissue. These cells are connected... more Cardiac fibroblasts are widely represented in mammalian cardiac tissue. These cells are connected with cardiomyocytes by gap junctions and they have own changeable membrane potential, so that fibroblasts can influence cardiomyocyte electrical activity. This effect may be analyzed in mathematical models. Existing mathematical models of fibroblast-cardiomyocyte interaction allow anyone to study only electrical responses of the cardiomyocytes and fibroblasts to their electrical interaction. In our work we have considered the fibroblast influence on the cardiomyocytes mechanics. In numerical experiments we reveal significant changes in the cardiomyocyte action potential duration and force depending on the number of fibroblast connected with the cardiomyocyte.
International Journal of Molecular Sciences, Apr 16, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Proceedings of the 31th International Conference on Computer Graphics and Vision. Volume 2, 2021
e intense movement of the heart and the presence of blood on surface, the application of the nece... more e intense movement of the heart and the presence of blood on surface, the application of the necessary small markers is rather difficult, and the use of luminous chemicals would harm physiological functioning. Moreover, these videos contain motion artifacts that complicate further analysis with Particle Image Velocimetry. In this paper, an image preprocessing algorithm was proposed. It is based on approximate tracking individual fragments using the Mean Squared Error for the matrix. The result is binary images where small points are built instead of each fragment. In this study, the proposed algorithm showed better results in comparison with the most suitable filtering methods for specific frames, namely, the Sobel filter and the Canny edge detector. This can be partially explained by the higher density of vector fields due to the absence of unreliable vectors. Thus, the proposed method, unlike others, allows to get vector fields with visible vortex-like mechanical movements.
Journal Online Supplement
Electrical Wave Propagation in an Anisotropic Model of the Left Ventricle Based on Analytical Description of Cardiac Architecture
We develop a numerical approach based on our recent analytical model of fiber structure in the le... more We develop a numerical approach based on our recent analytical model of fiber structure in the left ventricle of the human heart. A special curvilinear coordinate system is proposed to analytically include realistic ventricular shape and myofiber directions. With this anatomical model, electrophysiological simulations can be performed on a rectangular coordinate grid. We apply our method to study the effect of fiber rotation and electrical anisotropy of cardiac tissue (i.e., the ratio of the conductivity coefficients along and across the myocardial fibers) on wave propagation using the ten Tusscher–Panfilov (2006) ionic model for human ventricular cells. We show that fiber rotation increases the speed of cardiac activation and attenuates the effects of anisotropy. Our results show that the fiber rotation in the heart is an important factor underlying cardiac excitation. We also study scroll wave dynamics in our model and show the drift of a scroll wave filament whose velocity depend...
Effects of Mechanical Interaction Between Two Rabbit Cardiac Muscles Connected in Parallel
Abstract. The hypothesis that myocardium mechanical inhomogeneity produces a substantial effect o... more Abstract. The hypothesis that myocardium mechanical inhomogeneity produces a substantial effect on mechanical function was tested. Muscle inhomogeneity was studied in isolated papillary muscles or trabeculae excised from rabbit right ventricle and connected in a parallel duplex. Each muscle was placed in a separate perfusion bath. One end of each muscle was fastened to an individual force transducer and the other to the common lever of a servomotor. This arrangement allowed both muscles, being excited independently, to pull jointly a load applied to the lever. Separate electrodes for each perfusion bath allowed to stimulate muscles with a time delay. Tension developed in the individual muscles and their interaction were studied. Developed tension was critically dependent on the timing and sequence of excitation. Using mathematical modeling, patterns of tension distribution experimentally observed in parallel duplexes were simulated. These results suggest that changes both in Ca 2+ t...
Analysis of changes in the rat cardiovascular system under the action of lead intoxication and muscular exercise
Hygiene and sanitation
Introduction. One of the risk factors for cardiovascular diseases is the toxic metal pollution of... more Introduction. One of the risk factors for cardiovascular diseases is the toxic metal pollution of the industrial area and the environment. Lead is the most critical of toxic metals. In industrial conditions, the body’s exposure to harmful substances is often combined with muscular work of varying severity. It has not been studied enough how these combinations influence the development of pathological processes associated with harmful exposure. Materials and methods. The subchronic experiment was carried out on white outbred male rats for six weeks. Intoxication was simulated by repeated intraperitoneal injections of lead acetate three times a week. Running was chosen to model the muscle exercise at a 25 m/min speed for 10 minutes 5 days a week. We performed biochemical and electrocardiographic studies. Blood pressure parameters were recorded. Muscle contractility was studied on isolated multicellular preparations of the right ventricular myocardium in isometric and physiological con...
General Physiology and Biophysics, 2000
Earlier, we developed a mathematical model of myocardial contraction-relaxation cycle regulation.... more Earlier, we developed a mathematical model of myocardial contraction-relaxation cycle regulation. A great number of mechanical experiments was simulated in the model, the phenomenon of load dependent relaxation (LDR) included. In the present work we used the same model to analyze experimental data revealing that high temperature leads to reduction of LDR. We simulated three main factors arising due to high temperature, which a priori may cause LDR reduction: increasing the cross-bridges cycling rate, decreasing the duration of the Ca transient ascending limb, and increasing Ca pumping rate. Indeed, these factors together result in LDR reduction; i.e., the model correctly simulates the effect of high temperature on LDR in general. At the same time, the sensitivity of LDR to the third factor is much higher than to the first and the second ones; i.e., increasing the rate of Ca pumping is sufficient to induce the observed effect in the framework of the model. This seems to contrast with...
Original Contributions Cooperative Effects DuetoCalcium Binding byTroponin andTheirConsequences for Contraction andRelaxation ofCardiac MuscleUnderVarious Conditions ofMechanical Loading
A mathematical modelfortheregulation ofmechanical activity incardiac musclehasbeen developed base... more A mathematical modelfortheregulation ofmechanical activity incardiac musclehasbeen developed based on a three-element rheological modelofthis muscle. Thecontractile element hasbeenmodeled taking into account theresults ofextensive mechanical tests thatinvolved the recording oflength-force andforce-velocity relations andmuscle responses toshort-time deformations during various phases ofthecontraction-rela xation cycle. Thebestagreement between theexperimental andthemathematical modeling results was obtained whena postulate stating twotypes ofcooperativity toregulate thecalcium binding bytroponin was introduced into themodel. Cooperativity ofthefirst typeisduetothedependence oftheaffinity oftroponin C forCa2' on theconcentration ofmyosincrossbridges inthevicinity ofa given troponin C.Cooperativity ofthesecond typeassumes an increase intheaffinity ofa given troponin C forCa2' whenthelatter isboundbymolecules neighboring troponin. (Circulation Research 1991;69:1171-1184)
Uploads
Papers by Leonid Katsnelson