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.
Department of Physics, Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, California 92093-0319, USA. hherve@physics.ucsd.edu
Hervé
H
Henry
Wouter-Jan
WJ
Rappel
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*