AHEART April 47/4

Wang, Yan, and Yoram Rudy. Action potential propagation in inhomogeneous cardiac tissue: safety factor considerations and ionic mechanism. Am J Physiol Heart Circ Physiol 278: H1019–H1029, 2000.—Heterogeneity of myocardial structure and membrane excitability is accentuated by pathology and remodeling. In this study, a detailed model of the ventricular myocyte in a multicellular fiber was used to compute a location-dependent quantitative measure of conduction (safety factor, SF) and to determine the kinetics and contribution of sodium current (INa) and L-type calcium current [ICa(L)] during conduction. We obtained the following results. 1) SF decreases sharply for propagation into regions of increased electrical load (tissue expansion, increased gap junction coupling, reduced excitability, hyperkalemia); it can be ,1 locally (a value indicating conduction failure) and can recover beyond the transition region to resume propagation. 2) SF and propagation across inhomogeneities involve major contribution from ICa(L). 3) Modulating INa or ICa(L) (by blocking agents or calcium overload) can cause unidirectional block in the inhomogeneous region. 4) Structural inhomogeneity causes local augmentation of ICa(L) and suppression of INa in a feedback fashion. 5) Propagation across regions of suppressed INa is achieved via a ICa(L)-dependent mechanism. 6) Reduced intercellular coupling can effectively compensate for reduced SF caused by tissue expansion but not by reduced membrane excitability.