The Vulnerable Window for Unidirectional Block in Cardiac Tissue: Characterization and Dependence on Membrane Excitability and Intercellular Coupling

Vulnerable Window of Unidirectional Block. Introduction: 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. Methods and Results: 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, VW_time, and as a range of membrane potentials at the stimulus site, VW_pot VW_pot and VW_time, were quantified over a range of membrane excitability and gap junction resistances (intercellular coupling). With normal membrane excitability and intercellular coupling, VW_pot, and VW_time, were small (VW_Pot, = 0.44 mV, VW_time, = 0.39 msec). A uniform reduction (0.25 ×) in the degree of intercellular coupling increased VW_time, and VW_pot, by factors of 3.6 and 4.7, respectively, whereas a uniform decrease (0.25 ×) in membrane excitability (same resulting velocity) increased VW_time, by only a factor of 0.4 and decreased VW_pot, to negligible levels. When inhomogeneities in fiber properties were introduced (intercellular coupling and membrane excitability), VW_time, increased more due to inhomogeneity in membrane excitability (VW_time= 4.5 msec) than to inhomogeneity in intercellular coupling (VW_time, = 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 eiectrode length, to the intrinsic VW of the fiber. Conclusions: VW_pot, and VW_time, are both important parameters for quantifying vulnerability to unidirectional block. In an environment with uniform distribution of fiber and membrane properties, reduced intercellular coupling bas 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.