Abstract:
To determine the mechanical and energetic properties of the heart, experiments are commonly performed on both the whole organ and cardiac trabeculae. In both of these models, the sarcomere is the fundamental contractile unit of muscle, and is activated by calcium. Although the role of calcium in muscle contraction has been well characterised, there are currently no experimental data or computational models which describe its behavior during a work-loop. In this study, the ter Keurs calcium model was successfully paired with the Rice-Tran cross-bridge model. This allowed me to explore the behavior of the free cytosolic calcium concentration during the contractile cycle as well as to study more accurately the mechano-energetic behavior of sarcomere dynamics. The results made clear that as the force developed by the sarcomere waned during the relaxation phase of the twitch (in response to the decline of the calcium transient), Troponin-C released a portion of its bound Ca2+, thus producing a second surge in free cytosolic calcium. Such behaviour has been repeatedly observed in isometric, but not work-loop, contractions. Given the successful performance of the integrated cellular model, I implemented it within an existing model of the left ventricle. Simulations qualitatively reproduced general trends seen experimentally. Most importantly, pressure-volume loops produced by the 3-D, whole-heart model matched experimental data.