The cross-bridge dynamics during ventricular contraction predicted by coupling the cardiac cell model with a circulation model

Abstract

The force-velocity (F-V) relationship of filament sliding is traditionally used to define the inotropic condition of striated muscles. A simple circulation model combined with the Laplace heart was developed to get a deeper insight into the relationship between the F-V characteristics and the cardiac ventricular inotropy. The circulation model consists of a preload and an afterload compartments. The linear F-V relationship for filament sliding in the NL model (Negroni and Lascano 1996) was replaced by the exponential F-V relation observed by Piazzesi et al. (2002). We also modified the NL model to a hybrid model to benefit from the Ca2+ cooperativity described by the Robinson model (Robinson et al. 2002). The model was validated by determining the diastolic ventricular pressure-volume relationship of the Laplace heart and the F-V relation of the new hybrid model. The computed parameters of the cardiac cycle agreed well with the physiological data. Computational results showed that the cross-bridge elongation (h in the NL model) temporally undershot the equilibrium hc during the ejection period and overshot it during the rapid refilling phase. Thereby the time course of ejection and refilling was retarded. In a simulation where the velocity of the mobile myosin head (dX/dt) was varied, the systolic peak pressure of the ventricle varied from a minimum value at dX/dt = 0 to a saturating value obtained with a constant hc, providing in silico evidence for a functional impact of the cross-bridge sliding rate on the ventricular inotropy.