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An analysis of deformation‐dependent electromechanical coupling in the mouse heart
Author(s) -
Land Sander,
Niederer Steven A.,
Aronsen Jan Magnus,
Espe Emil K. S.,
Zhang Lili,
Louch William E.,
Sjaastad Ivar,
Sejersted Ole M.,
Smith Nicolas P.
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.231928
Subject(s) - biological system , coupling (piping) , contraction (grammar) , biomedical engineering , heart rate , heart cells , experimental data , biophysics , in vivo , computational model , cardiovascular physiology , chemistry , materials science , computer science , myocyte , blood pressure , biology , simulation , cardiology , mathematics , medicine , microbiology and biotechnology , statistics , metallurgy
Key points• The amount of force generated by heart cells is strongly influenced by feedback from the deformation of cardiac tissue, both from the changes in cell length and the rate at which cells are stretched. • We analysed the effect these cellular mechanisms have on whole heart function by making a computational model of mouse heart cells, and embedding this cellular model into a representation of the heart. • Unlike previous murine models, this model represents the heart at both body temperature and the high heart rates seen in these animals, allowing us to directly compare results from our computational model with experimental measurements. • Results show that effects from the rate of stretch are especially important for explaining the large differences observed between force generated by isolated cells and pressure measured experimentally. • The model also provides an important framework for future research focused on interpreting results from genetic manipulation experiments in mice.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.