Constancy and variability of contractile efficiency as a function of calcium and cross-bridge kinetics: simulation

We simulated myocardial Ca2+ (Ca) and cross-bridge (CB) kinetics to get insight into the experimentally observed constancy and variability of cardiac contractile efficiency in generating total mechanical energy under various inotropic and pathological conditions. The simulation consisted of a Ca transient, Ca association and dissociation rate constants of troponin C, and CB on and off rate constants. We evaluated sarcomere isometric twitch contractions at a constant muscle length. We assumed that each CB cycle hydrolyzes one ATP and that the force-length area (FLA) quantifies the total mechanical energy generated by CB cycles in a twitch contraction. FLA is a linear version of pressure-volume area, which quantifies the total mechanical energy of cardiac twitch contraction and correlates linearly with cardiac oxygen consumption (H. Suga, Physiol. Rev. 70: 247-277, 1990). The simulation shows that the contractile efficiency varies with changes in the Ca transient and Ca and CB kinetics except when they simultaneously speed up or slow down proportionally. These results point to possible mechanisms underlying the constancy and variability of cardiac contractile efficiency.