A thermodynamic transient cross-bridge model for prediction of contractility and remodelling of the ventricle.
J Mech Behav Biomed Mater
; 113: 104074, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33189012
ABSTRACT
Cardiac hypertrophy is an adaption of the heart to a change in cardiovascular loading conditions. The current understanding is that progression may be stress or strain driven, but the multi-scale nature of the cellular remodelling processes have yet to be uncovered. In this study, we develop a model of the contractile left ventricle, with the active cell tension described by a thermodynamically motivated cross-bridge cycling model. Simulation of the transient recruitment of myosin results in correct patterns of ventricular pressure predicted over a cardiac cycle. We investigate how changes in tissue loading and associated deviations in transient force generation can drive restructuring of cellular myofibrils in the heart wall. Our thermodynamic framework predicts in-series sarcomere addition (eccentric remodelling) in response to volume overload, and sarcomere addition in parallel (concentric remodelling) in response to valve and signalling disfunction. This framework provides a significant advance in the current understanding of the fundamental sub-sarcomere level biomechanisms underlying cardiac remodelling. Simulations reveal that pathological tissue loading conditions can significantly alter actin-myosin cross-bridge cycling over the course of the cardiac cycle. The resultant variation in sarcomere stress pushes an imbalance between the internal free energy of the myofibril and that of unbound contractile proteins, initiating remodelling. The link between cross-bridge thermodynamics and myofibril remodelling proposed in this study may significantly advance current understanding of cardiac disease onset.
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1
Base de dados:
MEDLINE
Assunto principal:
Ventrículos do Coração
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Modelos Cardiovasculares
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Contração Muscular
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
J Mech Behav Biomed Mater
Assunto da revista:
ENGENHARIA BIOMEDICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Irlanda