Page 93 - Cardiac Electrophysiology | A Modeling and Imaging Approach
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               Conceptually, there is no difference between

        the regional increase of coupling discussed above,
        fiber branching, or tissue expansion; they all
        introduce an increase of electrical load and a source-
        sink mismatch. Propagation across an expansion

        (branching) site is shown in Figure 3.13. Clearly, the
        behavior is strikingly similar to that in Figure 3.11,
        where the load increase at the transition was due                A
        to increased gap junction coupling. In fact, as was

        shown theoretically and experimentally,     218,219,220
        reduced coupling can compensate for increased
        loading due to tissue expansion and restore
        successful propagation. It should also be noted that

        the concepts of source, sink, loading and source-sink
        mismatch are not limited to structural properties, but
        apply to functional asymmetries as well. For example,
        a rotating wave front in a reentry circuit assumes a             B

        large curvature around pivot points and provides
        depolarizing current to a large volume of tissue
        (“fanning-out” effect), a situation of small source to
        large sink mismatch. A similar situation arises at the

        tip region of a spiral wave. In concept, these situations
        are the same as the increased loading due to greater
        intercellular coupling or tissue expansion presented in
        Figures 3.11 and 3.13.
                                                                         C

               The reliance of propagation in inhomogeneous
        tissue on I    when long conduction delays are
                   Ca,L
        present, was demonstrated experimentally.  I
                                                        221
                                                           Ca,L
        suppression by nifedipine (an I      blocker) leads to
                                          Ca,L
        conduction block under such circumstances.
        Conversely, I    enhancement by BAY K 8644 or
                      Ca,L
        isoproterenol (I    agonists) facilitates conduction
                         Ca,L
        across structural inhomogeneities. An example of
        such experiment is shown in Figure 3.14 , where                Figure 3.13. Propagation across an expan-
                                                    221
                                                                       sion (branching) site. Top diagram: fiber
        nifedipine produces unidirectional block at a site of          expansion is introduced at cell 80. A. AP;
        tissue expansion.                                              numbers indicate selected cells. B. SF
                                                                       along the fiber (line); bars show Q  and
                                                                                                            Na
                                                                       Q  at specific locations. C. Peak values of
                                                                         Ca
                                                                       I  and I Ca,L  along the fiber. ER, expansion
                                                                        Na
                                                                       ratio. From Wang and Rudy [218] courtesy
                                                                       of The American Physiological Society.
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