Abstract
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.
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References
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)
Noda, T., Shimizu, W., et al.: Classification and mechanism of Torsade de Pointes initiation in patients with congenital long QT syndrome. Eur. Heart J. 25(23), 2149–2154 (2004)
Viskin, S.: Long QT syndromes and torsade de pointes. Lancet 354(9190), 1625–1633 (1999)
Viskin, S., Alla, S.R., et al.: Mode of onset of torsade de pointes in congenital long QT syndrome. J. Am. Coll. Cardiol 28(5), 1262–1268 (1996)
Antzelevitch, C., Shimizu, W.: Cellular mechanisms underlying the long QT syndrome. Curr.Opin. Cardiol 17(1), 43–51 (2002)
Burashnikov, A., Antzelevitch, C.: Acceleration-induced action potential prolongation and early afterdepolarizations. J. Cardiovasc Electrophysiol 9(9), 934–948 (1998)
Akar, F.G., Yan, G.X., et al.: Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome. Circulation 105(10), 1247–1253 (2002)
Viskin, S.: Torsades de Pointes. Curr. Treat Options Cardiovasc Med. 1(2), 187–195 (1999)
Keating, M.T., Sanguinetti, M.C.: Molecular and cellular mechanisms of cardiac arrhythmias. Cell 104(4), 569–580 (2001)
Antzelevitch, C.: Molecular biology and cellular mechanisms of Brugada and long QT syndromes in infants and young children. J. Electrocardiol. 34 (Suppl.), 177–181 (2001)
Henry, H., Rappel, W.J.: The role of M cells and the long QT syndrome in cardiac arrhythmias: simulation studies of reentrant excitations using a detailed electrophysiological model. Chaos 14(1), 172–182 (2004)
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)
Gropp, W., Lusk, E., et al.: A high-performance, portable implementation of the MPI Message-Passing Interface standard. Parallel Computing 22(6), 789–828 (1996)
Clayton, R.H., Holden, A.V.: Dispersion of cardiac action potential duration and the initiation of re-entry: A computational study. Biomed. Eng. Online 4(1), 11 (2005)
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)
Nerbonne, J.M., Guo, W.: Heterogeneous expression of voltage-gated potassium channels in the heart: roles in normal excitation and arrhythmias. J. Cardiovasc Electrophysiol. 13(4), 406–409 (2002)
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)
Wolfram, S.: Cellular automata as models of complexity. Nature 311, 419–424 (1984)
Pormann, J. B., Henriquez, C.S., et al.: Computer Simulation of Cardiac Electrophysiology. In: Proc. SC 2000 (2000)
Huffaker, R., Lamp, S.T., et al.: Intracellular calcium cycling, early afterdepolarizations, and reentry in simulated long QT syndrome. Heart Rhythm 1(4), 441–448 (2004)
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)
Sanguinetti, M.C., Curran, M.E., et al.: Spectrum of HERG K+-channel dysfunction in an inherited cardiac arrhythmia. PNAS 93(5), 2208–2212 (1996)
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Wang, C., Krause, A., Nugent, C., Dubitzky, W. (2005). Focal Activity in Simulated LQT2 Models at Rapid Ventricular Pacing: Analysis of Cardiac Electrical Activity Using Grid-Based Computation. In: Oliveira, J.L., Maojo, V., MartÃn-Sánchez, F., Pereira, A.S. (eds) Biological and Medical Data Analysis. ISBMDA 2005. Lecture Notes in Computer Science(), vol 3745. Springer, Berlin, Heidelberg. https://doi.org/10.1007/11573067_31
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DOI: https://doi.org/10.1007/11573067_31
Publisher Name: Springer, Berlin, Heidelberg
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