Variable cross-bridge cycling-ATP coupling accounts for cardiac mechanoenergetics

Cardiac twitch contractions were simulated by Huxley's sliding filament cross-bridge muscle model coupled with parallel and series elastic components. The energetics of the contraction were based on the ATP hydrolysis for the cross-bridge cycling. Force-length area (FLA), as a measure of the total mechanical energy, was computed for both isometric and isotonic contractions in a manner similar to the pressure-volume area (PVA) (Suga, H. Physiol. Rev. 70: 247-277, 1990). PVA correlates linearly with cardiac oxygen consumption, and since FLA is analogous to PVA, FLA should correlate with the ATP expended. Simulations comparing FLA with the cross-bridge cycling ATP usage showed that at lower muscle fiber activation levels (shorter initial fiber lengths and lower preload levels) FLA decreased more rapidly than the number of muscle fiber cross-bridge cycles in both isometric and isotonic contraction cases. This suggests that one ATP can cause more than one cross-bridge cycle at lower activation levels as was proposed by Yanagida, Arata, and Oosawa (Nature 316: 366-369, 1985). If the number of cross-bridge cycles to ATP ratio is allowed to increase at lower activation levels as suggested by Yanagida et al., Huxley's model is compatible with the experimental findings on FLA and PVA.