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 the filament sliding is traditionally used to define the inotropic condition of striated muscles. To get a deeper insight into the relationship between the F-V characteristics and the cardiac ventricular inotropy, a simple circulation model combined with the Laplace heart was developed, and coupled with the circulation model consisting 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 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 h_c during the ejection period and overshot 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 h_c, providing in silico evidence for a functional impact of the cross-bridge sliding rate on the ventricular inotropy.