Key result
Simulation studies demonstrated that while early-after-depolarizations in M cells fail to initiate reentry due to electrotonic coupling, M cell domains can act as wave blocks to generate reentrant excitations.
Computational simulations demonstrate that M cell domains can act as wave blocks for premature stimuli, facilitating reentrant arrhythmias in the setting of long QT syndrome.
In this numerical study, we investigate the role of intrinsic heterogeneities of cardiac tissue due to M cells in the generation and maintenance of reentrant excitations using the detailed Luo-Rudy dynamic model. This model has been extended to include a description of the long QT 3 syndrome, and is studied in both one dimension, corresponding to a cable traversing the ventricular wall, and two dimensions, representing a transmural slice. We focus on two possible mechanisms for the generation of reentrant events. We first investigate if early-after-depolarizations occurring in M cells can initiate reentry. We find that, even for large values of the long QT strength, the electrotonic coupling between neighboring cells prevents early-after-depolarizations from creating a reentry. We then study whether M cell domains, with their slow repolarization, can function as wave blocks for premature stimuli. We find that the inclusion of an M cell domain can result in some cases in reentrant excitations and we determine the lifetime of the reentry as a function of the size and geometry of the domain and of the strength of the long QT syndrome.
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A 2004 study studied Cardiac arrhythmias and long QT syndrome. Simulation of M cell domains and long QT 3 syndrome vs. Homogeneous tissue models was evaluated on Generation of reentrant excitations. Simulation studies demonstrated that while early-after-depolarizations in M cells fail to initiate reentry due to electrotonic coupling, M cell domains can act as wave blocks to generate reentrant excitations.
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