Explaining load dependence of ventricular contractile properties with a model of excitation-contraction coupling

A theory is present which accounts for a very broad range of ventricular properties that have been noted in recent experiments. The theory is based upon a four-state biochemical scheme that accounts for the dynamic interaction between calcium, actin and myosin which includes a calcium-free force generating complex between actin and myosin. This original scheme was supplemented by incorporating two additional basic properties of cardiac muscle: length dependence of calcium binding affinity and load dependence of force generation. The biochemical scheme was used to provide the force-length-time properties of cardiac muscle which were used to construct a ventricle via a spherical geometry. In addition to being able to accurately interrelate previously measured calcium and muscle force transients, this theory was able to account for many fundamental aspects of ventricular performance including: a realistic contractility dependent curvilinearity of the end-systolic pressure-volume relationship: enhancement of contractile strength on ejecting compared to isovolumic beats; improved contractile efficiency on ejecting as compared to isovolumic beats; appropriate load-dependent changes in time to peak pressure, time constant of relaxation and duration of contraction on isovolumic and ejecting beats; realistic estimated time course of tension-dependent heat generation. The explanation for these phenomena were explored within the context of the theory and presented in detail.