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Focal Activity in Simulated LQT2 Models at Rapid Ventricular Pacing: Analysis of Cardiac Electrical Activity Using Grid-Based Computation

  • Chong Wang
  • Antje Krause
  • Chris Nugent
  • Werner Dubitzky
Part of the Lecture Notes in Computer Science book series (LNCS, volume 3745)

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.

Keywords

Cellular Automaton Premature Ventricular Contraction Endocardial Cell Rapid Ventricular Pace Basic Cycle Length 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 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
  2. 2.
    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)CrossRefGoogle Scholar
  3. 3.
    Viskin, S.: Long QT syndromes and torsade de pointes. Lancet 354(9190), 1625–1633 (1999)CrossRefGoogle Scholar
  4. 4.
    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)CrossRefGoogle Scholar
  5. 5.
    Antzelevitch, C., Shimizu, W.: Cellular mechanisms underlying the long QT syndrome. Curr.Opin. Cardiol 17(1), 43–51 (2002)CrossRefGoogle Scholar
  6. 6.
    Burashnikov, A., Antzelevitch, C.: Acceleration-induced action potential prolongation and early afterdepolarizations. J. Cardiovasc Electrophysiol 9(9), 934–948 (1998)CrossRefGoogle Scholar
  7. 7.
    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)CrossRefGoogle Scholar
  8. 8.
    Viskin, S.: Torsades de Pointes. Curr. Treat Options Cardiovasc Med. 1(2), 187–195 (1999)CrossRefGoogle Scholar
  9. 9.
    Keating, M.T., Sanguinetti, M.C.: Molecular and cellular mechanisms of cardiac arrhythmias. Cell 104(4), 569–580 (2001)CrossRefGoogle Scholar
  10. 10.
    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)CrossRefGoogle Scholar
  11. 11.
    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)CrossRefGoogle Scholar
  12. 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
  13. 13.
    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)zbMATHCrossRefGoogle Scholar
  14. 14.
    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)CrossRefGoogle Scholar
  15. 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
  16. 16.
    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)CrossRefGoogle Scholar
  17. 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
  18. 18.
    Wolfram, S.: Cellular automata as models of complexity. Nature 311, 419–424 (1984)CrossRefGoogle Scholar
  19. 19.
    Pormann, J. B., Henriquez, C.S., et al.: Computer Simulation of Cardiac Electrophysiology. In: Proc. SC 2000 (2000) Google Scholar
  20. 20.
    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)CrossRefGoogle Scholar
  21. 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
  22. 22.
    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)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • Chong Wang
    • 1
  • Antje Krause
    • 1
  • Chris Nugent
    • 2
  • Werner Dubitzky
    • 2
  1. 1.University of Applied Sciences WildauWildauGermany
  2. 2.University of UlsterUK

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