Hierarchical modeling of force generation in cardiac muscle

Performing physiologically relevant simulations of the beating heart in clinical context requires to develop detailed models of the microscale force generation process. These models, however, may reveal difficult to implement in practice due to their high computational costs and complex calibration. We propose a hierarchy of three interconnected muscle contraction models-from the more refined to the more simplified-that are rigorously and systematically related to each other, offering a way to select, for a specific application, the model that yields a good trade-off between physiological fidelity, computational cost and calibration complexity. The three model families are compared to the same set of experimental data to systematically assess what physiological indicators can be reproduced or not and how these indicators constrain the model parameters. Finally, we discuss the applicability of these models for heart simulation.