To relate the subcellular molecular events to organ level physiology in heart, we have developed a three-dimensional finite-element-based simulation program incorporating the cellular mechanisms of excitation-contraction coupling and its propagation, and simulated the fluid-structure interaction involved in the contraction and relaxation of the human left ventricle. The FitzHugh-Nagumo model and four-state model representing the cross-bridge kinetics were adopted for cellular model. Both ventricular wall and blood in the cavity were modeled by finite element mesh. An arbitrary Lagrangian Eulerian finite element method with automatic mesh updating has been formulated for large domain changes, and a strong coupling strategy has been taken. Using electrical analog of pulmonary circulation and left atrium as a preload and the windkessel model as an afterload, dynamics of ventricular filling as well as ejection was simulated. We successfully reproduced the biphasic filling flow consisting of early rapid filling and atrial contraction similar to that reported in clinical observation. Furthermore, fluid-structure analysis enabled us to analyze the wave propagation velocity of filling flow. This simulator can be a powerful tool for establishing a link between molecular abnormality and the clinical disorder at the macroscopic level.
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