A mathematical model for active contraction in healthy and failing myocytes and left ventricles

Cai, L., Wang, Y., Gao, H. , Li, Y. and Luo, X. (2017) A mathematical model for active contraction in healthy and failing myocytes and left ventricles. PLoS ONE, 12(4), e0174834. (doi: 10.1371/journal.pone.0174834) (PMID:28406991) (PMCID:PMC5391010)

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Cardiovascular disease is one of the leading causes of death worldwide, in particular myocardial dysfunction, which may lead to heart failure eventually. Understanding the electro-mechanics of the heart will help in developing more effective clinical treatments. In this paper, we present a multi-scale electro-mechanics model of the left ventricle (LV). The Holzapfel-Ogden constitutive law was used to describe the passive myocardial response in tissue level, a modified Grandi-Pasqualini-Bers model was adopted to model calcium dynamics in individual myocytes, and the active tension was described using the Niederer-Hunter-Smith myofilament model. We first studied the electro-mechanics coupling in a single myocyte in the healthy and diseased left ventricle, and then the single cell model was embedded in a dynamic LV model to investigate the compensation mechanism of LV pump function due to myocardial dysfunction caused by abnormality in cellular calcium dynamics. The multi-scale LV model was solved using an in-house developed hybrid immersed boundary method with finite element extension. The predictions of the healthy LV model agreed well with the clinical measurements and other studies, and likewise, the results in the failing states were also consistent with clinical observations. In particular, we found that a low level of intracellular Ca2+ transient in myocytes can result in LV pump function failure even with increased myocardial contractility, decreased systolic blood pressure, and increased diastolic filling pressure, even though they will increase LV stroke volume. Our work suggested that treatments targeted at increased contractility and lowering the systolic blood pressure alone are not sufficient in preventing LV pump dysfunction, restoring a balanced physiological Ca2+ handling mechanism is necessary.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Luo, Professor Xiaoyu and Gao, Dr Hao and Cai, Dr Li
Authors: Cai, L., Wang, Y., Gao, H., Li, Y., and Luo, X.
College/School:College of Science and Engineering > School of Mathematics and Statistics > Mathematics
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2017 Cai et al
First Published:First published in PLoS One 12(4): e0174834
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
694461EPSRC Centre for Multiscale soft tissue mechanics with application to heart & cancerRaymond OgdenEngineering & Physical Sciences Research Council (EPSRC)EP/N014642/1M&S - MATHEMATICS
560111Finite element-immersed boundary method and its application to mitral valvesXiaoyu LuoEngineering & Physical Sciences Research Council (EPSRC)EP/I029990/1M&S - MATHEMATICS