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.