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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: 18-01-00059 ; The 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.

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-A18-118020590031-8 ; Russian Foundation for Basic Research, RFBR: 18-01-00059 ; Russian Science Foundation, RSF: 18-74-10059 ; Funding. 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).

Rotating spiral waves of electrical excitation underlie many dangerous cardiac arrhythmias. The heterogeneity of myocardium is one of the factors that affects the dynamics of such waves. In this paper, we present results of our simulations for scroll wave dynamics in a heterogeneous model of the human left ventricle with analytical anatomically based representation of the geometry and anisotropy. We used a set of 18 coupled differential equations developed by ten Tusscher and Panfilov (TP06 model) which describes human ventricular cells based on their measured biophysical properties. We found that apicobasal heterogeneity dramatically changes the scroll wave dynamics. In the homogeneous model, the scroll wave annihilates at the base, but the moderate heterogeneity causes the wave to move to the apex and then continuously rotates around it. The rotation speed increased with the degree of the heterogeneity. However, for large heterogeneity, we observed formation of additional wavebreaks and the onset of complex spatio-temporal patterns. Transmural heterogeneity did not change the dynamics and decreased the lifetime of the scroll wave with an increase in heterogeneity. Results of our numerical experiments show that the apex may be a preferable location of the scroll wave, which may be important for development of clinical interventions. © 2020 by the authors. ; AAAA-A18-118020590031-8 ; Russian Foundation for Basic Research, RFBR: 18-29-13008 ; Russian Science Foundation, RSF: 14-35-00005 ; Ural Federal University, UrFU ; P.K., S.P., O.S., and A.V.P. were funded by the Russian Science Foundation (project 14-35-00005). A.V.P., P.K., and O.S. were funded by the Russian Foundation for Basic Research (#18-29-13008). A.V.P. and O.S. were funded by RF Government Act #211 of 16 March 2013 (agreement 02. A03.21.0006). P.K. and O.S. work was carried out within the framework of the IIF UrB RAS theme No. AAAA-A18-118020590031-8. A.V.P. and H.D. were partially funded by BOF Ghent University. Simulations were performed at the supercomputer Uran of Institute of Mathematics and Mechanics (Ekaterinburg, Russia) and at the supercomputer of Ural Federal University (Ekaterinburg, Russia).

This paper reviews the development and application of paired muscle preparations, called duplex, for the investigation of mechanisms and consequences of intra-myocardial electro-mechanical heterogeneity. We illustrate the utility of the underlying combined experimental and computational approach for conceptual development and integration of basic science insight with clinically relevant settings, using previously published and new data. Directions for further study are identified. © 2014 The Authors. ; The authors gratefully acknowledge the kind help of Mrs. Katherine Fletcher with careful revision of the text, and research support from the Ural Branch of the RAS ( 12-M-14-2009 , 12-П-4-1067 ), Programme #1 of Basic Research of the Presidium of RAS, Ural Federal University (No.211 Decree of the Government of RF of 16th March 2013), and the Russian Foundation for Basic Research ( 14-01-31134 , 14-01-00885 ). PK is a Senior Research Fellow of the British Heart Foundation and supported by a European Research Council Advanced Grant (CardioNect). Appendix A