The vulnerable window for unidirectional block in cardiac tissue: characterization and dependence on membrane excitability and intercellular coupling.

Abstract

Unidirectional block is a requisite event in the initiation of reentry in cardiac tissue, but its initiation and behavior in the presence of tissue pathologies remain poorly understood. Previous experimental and theoretical reports on vulnerability to unidirectional block under conditions of reduced cellular coupling and reduced membrane excitability have varied due to differences in experimental and simulation protocols. We have addressed the issue of vulnerability to unidirectional block using the recent Luo-Rudy membrane model and computer simulations of propagation in a one-dimensional cardiac fiber. The vulnerable window (VW) of unidirectional block from premature stimulation is expressed in units of time, VWtime, and as a range of membrane potentials at the stimulus site, VWpot. VWpot and VWtime were quantified over a range of membrane excitability and gap junction resistances (intercellular coupling). With normal membrane excitability and intercellular coupling, VWpot and VWtime were small (VWpot = 0.44 mV, VWtime = 0.39 msec). A uniform reduction (0.25x) in the degree of intercellular coupling increased VWtime and VWpot by factors of 3.6 and 4.7, respectively, whereas a uniform decrease (0.25x) in membrane excitability (same resulting velocity) increased VWtime by only a factor of 0.4 and decreased VWpot to negligible levels. When inhomogeneities in fiber properties were introduced (intercellular coupling and membrane excitability), VWtime increased more due to inhomogeneity in membrane excitability (VWtime = 4.5 msec) than to inhomogeneity in intercellular coupling (VWtime = 1.5 msec). The simulations also clarify the dependence of the VW on the dimensions of the stimulating electrode. The length of the stimulating electrode added a factor, equal to the propagation time across the electrode length, to the intrinsic VW of the fiber. VWpot and VWtime are both important parameters for quantifying vulnerability to unidirectional block. In an environment with uniform distribution of fiber and membrane properties, reduced intercellular coupling has a greater effect on the VW than reduced membrane excitability. Inhomogeneous reduction of membrane excitability can significantly enhance vulnerability to unidirectional block, much more so than inhomogeneous reduction of intercellular coupling. Theoretically, stimulation at a point should be used to define the VW. Finite electrode dimensions introduce a geometrical factor that affects the measurement of the VW.