title: An analysis of deformation-dependent electromechanical coupling in the mouse heart.
abstract: To investigate the effects of the coupling between excitation and contraction on whole-organ function, we have developed a novel biophysically based multiscale electromechanical model of the murine heart. Through comparison with a comprehensive in vivo experimental data set, we show good agreement with pressure and volume measurements at both physiological temperatures and physiological pacing frequencies. This whole-organ model was used to investigate the effects of material and haemodynamic properties introduced at the tissue level, as well as emergent function of our novel cell contraction model. Through a comprehensive sensitivity analysis at both the cellular and whole organ level, we demonstrate the sensitivity of the model's results to its parameters and the constraining effect of experimental data. These results demonstrate the fundamental importance of length- and velocity-dependent feedback to the cellular scale for whole-organ function, and we show that a strong velocity dependence of tension is essential for explaining the differences between measured single cell tension and whole-organ pressure transients.
authors.affiliation: Department of Computer Science, University of Oxford, Oxford, UK.
authors.forename: Sander
authors.initials: S
authors.lastname: Land
authors.forename: Steven A
authors.initials: SA
authors.lastname: Niederer
authors.forename: Jan Magnus
authors.initials: JM
authors.lastname: Aronsen
authors.forename: Emil K S
authors.initials: EK
authors.lastname: Espe
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: William E
authors.initials: WE
authors.lastname: Louch
authors.forename: Ivar
authors.initials: I
authors.lastname: Sjaastad
authors.forename: Ole M
authors.initials: OM
authors.lastname: Sejersted
authors.forename: Nicolas P
authors.initials: NP
authors.lastname: Smith
mesh_terms: D000818:Animals; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics; D051379:Mice; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*