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 ge t insight into the experimentally observed constancy and variability o f cardiac contractile efficiency in generating total mechanical energy under various inotropic and pathological conditions. The simulation c onsisted of a Ca transient, Ca association and dissociation rate const ants of troponin C, and CB on and off rate constants. We evaluated sar comere isometric twitch contractions at a constant muscle length. We a ssumed that each CB cycle hydrolyzes one ATP and that the force-length area (FLA) quantifies the total mechanical energy generated by CB cyc les in a twitch contraction. FLA is a Linear version of pressure-volum e 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 t he contractile efficiency varies with changes in the Ca transient and Ca and CB kinetics except when they simultaneously speed up or slow do wn proportionally. These results point to possible mechanisms underlyi ng the constancy and variability of cardiac contractile efficiency.