Focal Activity in Simulated LQT2 Models at Rapid Ventricular Pacing: Analysis of Cardiac Electrical Activity Using Grid-Based Computation
This study investigated the involvement of ventricular focal activity and dispersion of repolarization in LQT2 models at rapid rates. The Luo-Rudy dynamic model was used to simulate ventricular tissues. LQT2 syndrome due to genetic mutations was modeled by modifying the conductances of delayed rectifier potassium currents. Cellular automata was employed to generate virtual tissues coupled with midmyocardial (M) cell clusters. Simulations were conducted using grid-based computation. Under LQT2 conditions, early after-depolarizations (EADs) occurred first at the border of the M refractory zone in epicardium coupled with M clusters, but spiked off from endocardial cells in endocardium coupled with M clusters. The waveform of EADs was affected by the topological distribution of M clusters. Our results explain why subepicardial and subendocardial cells could exhibit surprisingly EADs when adjacent to M cells and suggest that phase 2 EADs are responsible for the onset of Torsade de Pointes at rapid ventricular pacing.
KeywordsCellular Automaton Premature Ventricular Contraction Endocardial Cell Rapid Ventricular Pace Basic Cycle Length
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- 1.Roden, D.M., Lazzara, R., et al.: Multiple Mechanisms in the Long-QT Syndrome: Current Knowledge, Gaps, and Future Directions. Circulation 94(8), 1996–2012 (1996)Google Scholar
- 12.Anyukhovsky, E.P., Sosunov, E.A., Rosen, M.R.: Regional Differences in Electrophysiological Properties of Epicardium, Midmyocardium, and Endocardium: In Vitro and In Vivo Correlations. Circulation 94(8), 1981–1988 (1996)Google Scholar
- 15.Luo, C.H., Rudy, Y.: A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Circ. Res. 74(6), 1071–1096 (1994)Google Scholar
- 17.Viswanathan, P.C., Shaw, R.M., Rudy, Y.: Effects of IKr and IKs heterogeneity on action potential duration and its rate dependence: a simulation study. Circulation 99(18), 2466–2474 (1999)Google Scholar
- 19.Pormann, J. B., Henriquez, C.S., et al.: Computer Simulation of Cardiac Electrophysiology. In: Proc. SC 2000 (2000) Google Scholar
- 21.Yan, G.X., Wu, Y., et al.: Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome: direct evidence from intracellular recordings in the intact left ventricular wall. Circulation 103(23), 2851–2856 (2001)Google Scholar