Suchergebnisse

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.

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: 18‑01‑00059 ; The 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.

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