In a computational model of the rat left ventricle, length-dependent Ca2+ sensitivity and filament overlap (the Frank-Starling Law) were identified as the dominant regulators of efficient cellular work transduction.
Computational modeling of the rat left ventricle demonstrates that length-dependent calcium sensitivity and filament overlap are the dominant regulators of efficient work transduction.
We have developed a multi-scale biophysical electromechanics model of the rat left ventricle at room temperature. This model has been applied to investigate the relative roles of cellular scale length dependent regulators of tension generation on the transduction of work from the cell to whole organ pump function. Specifically, the role of the length dependent Ca(2+) sensitivity of tension (Ca(50)), filament overlap tension dependence, velocity dependence of tension, and tension dependent binding of Ca(2+) to Troponin C on metrics of efficient transduction of work and stress and strain homogeneity were predicted by performing simulations in the absence of each of these feedback mechanisms. The length dependent Ca(50) and the filament overlap, which make up the Frank-Starling Law, were found to be the two dominant regulators of the efficient transduction of work. Analyzing the fiber velocity field in the absence of the Frank-Starling mechanisms showed that the decreased efficiency in the transduction of work in the absence of filament overlap effects was caused by increased post systolic shortening, whereas the decreased efficiency in the absence of length dependent Ca(50) was caused by an inversion in the regional distribution of strain.
Niederer et al. (Thu,) reported a other. Computational simulation (absence of tension and deformation feedback mechanisms) vs. Normal model (all mechanisms present) was evaluated on Efficient transduction of work (ratio of positive work to total work). In a computational model of the rat left ventricle, length-dependent Ca2+ sensitivity and filament overlap (the Frank-Starling Law) were identified as the dominant regulators of efficient cellular work transduction.