The role of M cells and the long QT syndrome in cardiac arrhythmias: simulation studies of reentrant excitations using a detailed electrophysiological model.
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.
Henry
Hervé
H
Department of Physics, Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, California 92093-0319, USA. hherve@physics.ucsd.edu
Rappel
Wouter-Jan
WJ
D000200:Action Potentials; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D003198:Computer Simulation; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D008133:Long QT Syndrome / Q000503:physiopathology*; D008564:Membrane Potentials; D008955:Models, Cardiovascular; D008959:Models, Neurological; D032383:Myocytes, Cardiac; D017711:Nonlinear Dynamics; D009435:Synaptic Transmission; D013611:Tachycardia, Atrioventricular Nodal Reentry / Q000503:physiopathology*