Cargando…

Frank-Starling mechanism, fluid responsiveness, and length-dependent activation: Unravelling the multiscale behaviors with an in silico analysis

The Frank-Starling mechanism is a fundamental regulatory property which underlies the cardiac output adaptation to venous filling. Length-dependent activation is generally assumed to be the cellular origin of this mechanism. At the heart scale, it is commonly admitted that an increase in preload (ve...

Descripción completa

Detalles Bibliográficos
Autores principales: Kosta, Sarah, Dauby, Pierre C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504729/
https://www.ncbi.nlm.nih.gov/pubmed/34634040
http://dx.doi.org/10.1371/journal.pcbi.1009469
_version_ 1784581377810759680
author Kosta, Sarah
Dauby, Pierre C.
author_facet Kosta, Sarah
Dauby, Pierre C.
author_sort Kosta, Sarah
collection PubMed
description The Frank-Starling mechanism is a fundamental regulatory property which underlies the cardiac output adaptation to venous filling. Length-dependent activation is generally assumed to be the cellular origin of this mechanism. At the heart scale, it is commonly admitted that an increase in preload (ventricular filling) leads to an increased cellular force and an increased volume of ejected blood. This explanation also forms the basis for vascular filling therapy. It is actually difficult to unravel the exact nature of the relationship between length-dependent activation and the Frank-Starling mechanism, as three different scales (cellular, ventricular and cardiovascular) are involved. Mathematical models are powerful tools to overcome these limitations. In this study, we use a multiscale model of the cardiovascular system to untangle the three concepts (length-dependent activation, Frank-Starling, and vascular filling). We first show that length-dependent activation is required to observe both the Frank-Starling mechanism and a positive response to high vascular fillings. Our results reveal a dynamical length dependent activation-driven response to changes in preload, which involves interactions between the cellular, ventricular and cardiovascular levels and thus highlights fundamentally multiscale behaviors. We show however that the cellular force increase is not enough to explain the cardiac response to rapid changes in preload. We also show that the absence of fluid responsiveness is not related to a saturating Frank-Starling effect. As it is challenging to study those multiscale phenomena experimentally, this computational approach contributes to a more comprehensive knowledge of the sophisticated length-dependent properties of cardiac muscle.
format Online
Article
Text
id pubmed-8504729
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-85047292021-10-12 Frank-Starling mechanism, fluid responsiveness, and length-dependent activation: Unravelling the multiscale behaviors with an in silico analysis Kosta, Sarah Dauby, Pierre C. PLoS Comput Biol Research Article The Frank-Starling mechanism is a fundamental regulatory property which underlies the cardiac output adaptation to venous filling. Length-dependent activation is generally assumed to be the cellular origin of this mechanism. At the heart scale, it is commonly admitted that an increase in preload (ventricular filling) leads to an increased cellular force and an increased volume of ejected blood. This explanation also forms the basis for vascular filling therapy. It is actually difficult to unravel the exact nature of the relationship between length-dependent activation and the Frank-Starling mechanism, as three different scales (cellular, ventricular and cardiovascular) are involved. Mathematical models are powerful tools to overcome these limitations. In this study, we use a multiscale model of the cardiovascular system to untangle the three concepts (length-dependent activation, Frank-Starling, and vascular filling). We first show that length-dependent activation is required to observe both the Frank-Starling mechanism and a positive response to high vascular fillings. Our results reveal a dynamical length dependent activation-driven response to changes in preload, which involves interactions between the cellular, ventricular and cardiovascular levels and thus highlights fundamentally multiscale behaviors. We show however that the cellular force increase is not enough to explain the cardiac response to rapid changes in preload. We also show that the absence of fluid responsiveness is not related to a saturating Frank-Starling effect. As it is challenging to study those multiscale phenomena experimentally, this computational approach contributes to a more comprehensive knowledge of the sophisticated length-dependent properties of cardiac muscle. Public Library of Science 2021-10-11 /pmc/articles/PMC8504729/ /pubmed/34634040 http://dx.doi.org/10.1371/journal.pcbi.1009469 Text en © 2021 Kosta, Dauby https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kosta, Sarah
Dauby, Pierre C.
Frank-Starling mechanism, fluid responsiveness, and length-dependent activation: Unravelling the multiscale behaviors with an in silico analysis
title Frank-Starling mechanism, fluid responsiveness, and length-dependent activation: Unravelling the multiscale behaviors with an in silico analysis
title_full Frank-Starling mechanism, fluid responsiveness, and length-dependent activation: Unravelling the multiscale behaviors with an in silico analysis
title_fullStr Frank-Starling mechanism, fluid responsiveness, and length-dependent activation: Unravelling the multiscale behaviors with an in silico analysis
title_full_unstemmed Frank-Starling mechanism, fluid responsiveness, and length-dependent activation: Unravelling the multiscale behaviors with an in silico analysis
title_short Frank-Starling mechanism, fluid responsiveness, and length-dependent activation: Unravelling the multiscale behaviors with an in silico analysis
title_sort frank-starling mechanism, fluid responsiveness, and length-dependent activation: unravelling the multiscale behaviors with an in silico analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504729/
https://www.ncbi.nlm.nih.gov/pubmed/34634040
http://dx.doi.org/10.1371/journal.pcbi.1009469
work_keys_str_mv AT kostasarah frankstarlingmechanismfluidresponsivenessandlengthdependentactivationunravellingthemultiscalebehaviorswithaninsilicoanalysis
AT daubypierrec frankstarlingmechanismfluidresponsivenessandlengthdependentactivationunravellingthemultiscalebehaviorswithaninsilicoanalysis