Incorporating histology into a 3D microscopic computer model of myocardium to study propagation at a cellular level.

We introduce a 3D model of cardiac tissue to study at a microscopic level the relationship between tissue morphology and propagation of depolarization. Unlike the classical bidomain approach, in which tissue properties are described by the apparent conductivity of the tissue, in this "microdomain" approach, we included histology by modeling the actual shape of the intracellular and extracellular spaces that contain spatially distributed gap-junctions and membranes. The histological model of the tissue was generated by a computer algorithm that can be tuned to model different histological changes. For healthy tissue, the model predicted a realistic conduction velocity of 0.42 m/s based solely on the parameters derived from histology. A comparison with a brick-shaped, simplified model showed that conduction depended to a moderate extent on the shape of myocytes; a comparison with a one-dimensional bidomain model with the same overall shape and structure showed that the apparent conductivity of the tissue can be used to create an equivalent bidomain model. In summary, the microdomain approach offers a means of directly incorporating structural and functional parameters into models of cardiac activation and propagation and thus provides a valuable bridge between the cellular and tissue domains in the myocardium.