THE VULNERABLE WINDOW FOR UNIDIRECTIONAL BLOCK IN CARDIAC TISSUE - CHARACTERIZATION AND DEPENDENCE ON MEMBRANE EXCITABILITY AND INTERCELLULAR COUPLING

Introduction: Unidirectional block is a requisite event in the initiat ion of reentry in cardiac tissue, but its initiation and behavior in t he presence of tissue pathologies remain poorly understood. Previous e xperimental and theoretical reports on vulnerability to unidirectional block under conditions of reduced cellular coupling and reduced membr ane excitability have varied due to differences in experimental and si mulation protocols. Methods and Results: We have addressed the issue o f vulnerability to unidirectional block using the recent Luo-Rudy memb rane model and computer simulations of propagation in a one-dimensiona l cardiac fiber. The vulnerable window (VW) of unidirectional block fr om 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 ex citability and intercellular coupling, VWpot and VWtime were small (VW pot = 0.44 mV, VWtime = 0.39 msec). A uniform reduction (0.25X) in the degree of intercellular coupling increased VWtime and VWpot by factor s of 3.6 and 4.7, respectively, whereas a uniform decrease (0.25X) in membrane excitability (same resulting velocity) increased VWtime by on ly a factor of 0.4 and decreased VWpot to negligible levels. When inho mogeneities in fiber properties were introduced (intercellular couplin g and membrane excitability), VWtime increased more due to inhomogenei ty in membrane excitability (VWtime = 4.5 msec) than to inhomogeneity in intercellular coupling (VWtime = 1.5 msec). The simulations also cl arify the dependence bf the VW on the dimensions of the stimulating el ectrode. 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. Conclusions: VWpot and VWtime are both important par ameters for quantifying vulnerability to unidirectional block. In an e nvironment with uniform distribution of fiber and membrane properties, reduced intercellular coupling has a greater effect on the VW than re duced membrane excitability. Inhomogeneous reduction of membrane excit ability can significantly enhance vulnerability to unidirectional bloc k, much more so than inhomogeneous reduction of intercellular coupling . Theoretically, stimulation at a point should be used to define the V W. Finite electrode dimensions introduce a geometrical factor that aff ects the measurement of the VW.