Journal
JOURNAL OF PHYSIOLOGY-LONDON
Volume 590, Issue 18, Pages 4553-4569Publisher
WILEY-BLACKWELL
DOI: 10.1113/jphysiol.2012.231928
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Funding
- MRC (Medical Research Council) [G0800980]
- EPSRC (Engineering and Physical Sciences Research Council) [EP/F043929/1, EP/G007527/2]
- Research Council of Norway
- South-Eastern Norway Regional Health Authority
- Norwegian Health Association
- Oslo University Hospital Ulleval, University of Oslo
- European Union [FP7-HEALTH-2010.2.4.2-4]
- Engineering and Physical Sciences Research Council [EP/F043929/1] Funding Source: researchfish
- Medical Research Council [G0800980] Funding Source: researchfish
- EPSRC [EP/F043929/1] Funding Source: UKRI
- MRC [G0800980] Funding Source: UKRI
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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.
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