Effect of heterogeneities in the cellular microstructure on propagation of the cardiac action potential.

Cardiac arrhythmias are initiated in regions that undergo cellular remodeling as a result of disease. Using a sub-cellular model of myocardium, we studied the mechanism of block caused by tissue microstructure remodeling: cell geometry [quantified as length/width (L/W) cell ratio] and cell-to-cell coupling (G(j)). Heterogeneities in cell L/W ratio and G ( j ) lead to block when excitability is reduced and the corresponding space constant λ (in the direction of propagation) increases by >40 %. Tissue architectures with elongated cells (i.e. large cell L/W ratios) that are better coupled (i.e. large G(j)) are less prone to block at sites of regional heterogeneities in cell geometry and/or cell coupling than tissue architectures consisting of cells with smaller L/W ratios and/or poorer coupling. Whether an increase in tissue anisotropic ratio (ANR) is arrhythmogenic or not depends on the cellular mechanism of the increase: ANR leads to an increased risk of block when G(j) decreases, but to a decreased risk of block when cell L/W ratio increases. Our findings are useful to understand the mechanisms of block in cardiac pathologies that result in tissue architecture remodeling.