When ventricular myocardium activates in vivo, it generates force under near isometric conditions until the pressure in the chamber equals the pressure in the associated artery. Further increases in pressure open the valve leading out of the ventricle and eject blood into the circulation. This type of activation can be mimicked in vitro using an afterload protocol in which a muscle preparation is stimulated to contract isometrically until force reaches a pre-defined setpoint. Thereafter, the muscle shortens against the target load. A force-velocity curve for the muscle can then be generated by running subsequent tests with different target loads. Alternatively, a muscle can be activated, held isometric until peak force is developed, and then released to shorten against the same set of target loads. This technique also produces a hyperbolic force-velocity curve but experiments typically show this approach produces a higher shortening velocity for a given load. The power produced by the muscle thus depends on the experimental protocol and is higher when the preparation is released from near maximum force. This behavior is well-known experimentally but deviates from the predictions of conventional Huxley-type cross-bridge distribution models. The current work simulated the two experimental protocols using a open-source spatially explicit computer model of myofilaments called FiberSim. Importantly, the simulations reproduced the experimental result where afterloaded contractions generated less power. Analysis of the simulations showed that the reduced power resulted from decreased activation of the myofilaments. Specifically, during afterloaded contractions, sarcomeres started to shorten (and thus deactivated as myosin heads detached) before they had reached maximal activation. Muscles that were released from peak force shortened initially with more binding sites available on thin filaments and thus contracted more quickly.
Campbell et al. (Sun,) studied this question.