Abstract
We have developed a multi-scale biophysical electromechanics model of the rat left ventricle at room temperature. This model has been used to investigate the role of length dependent regulators of tension in the transduction of cellular work into whole organ pump function. Specifically the role of the length dependent Ca2+ sensitivity of tension (Ca50), filament overlap tension dependence, velocity dependence of tension and tension dependent binding of Ca2+ to Troponin C on metrics of effective transduction of work were predicted by performing simulations in the absence of each of these feedback mechanisms. The length dependent Ca50 and the filament overlap, which make up the Frank-Starling effect, were found to be the two dominant regulators of effective transduction of work. Analyzing the fiber velocity field in the absence of the Frank-Starling mechanisms showed that transduction of work from the cell to the whole organ in the absence of filament overlap effects was caused by increased post systolic shortening, whereas the decrease in efficiency observed in the absence of length dependent Ca50 was caused by an inversion in the regional distribution of strain.
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