Skip to main content

Study of Polymorphic Ventricular Tachycardia in a 2D Cardiac Transmural Tissue

  • Conference paper
  • First Online:
ICTMI 2017

Abstract

Beta-adrenergic agents are usually contraindicated in patients prone to acquired Torsade de Pointes (TdP). TdP is frequently accompanied by long QT syndrome 2 (LQTS2). Here, we try to simulate TdP in a 2D transmural grid in presence of the above two conditions. Modifications to the TP06 model are made to emulate the differences in action potential (AP) generated from the three types of transmural cells (endocardial, mid- and epicardial cells). The effect of drug-induced LQTS2 is evoked by completely blocking the rapid delayed rectifier potassium current (IKr) in each cell, and beta-adrenergic stimulation is introduced by raising the conductance of l-type calcium current (GCaL) to twice its normal value. This combined effect increases the inducibility of early afterdepolarizations (EADs). The mechanism of EAD generation at cellular level is studied by analysing the ionic currents and calcium dynamics. TdP like polymorphic ventricular arrhythmia is found to develop under slow pacing rates. Spontaneous release of calcium from the sarcoplasmic reticulum triggers an increase in the level of intracellular calcium and inward sodium current through the sodium-calcium exchanger current (INaCa). This prolongs the action potential duration (APD) providing enough time to reactivate ICaL creating an upstroke during the repolarization phase.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Adeniran I, McPate MJ, Witchel HJ, Hancox JC, Zhang H (2011) Increased vulnerability of human ventricle to re-entrant excitation in hERG-linked variant 1 short QT syndrome. PLoS Comput Biol 7(12):e1002313

    Article  Google Scholar 

  2. Antoons G, Johnson DM, Dries E, Santiago DJ, Ozdemir S, Lenaerts I, Beekman JD, Houtman MJ, Sipido KR, Vos MA (2015) Calcium release near l-type calcium channels promotes beat-to-beat variability in ventricular myocytes from the chronic AV block dog. J Mol Cellular Cardiol 89:326–334

    Article  Google Scholar 

  3. Antzelevitch C (2007) Ionic, molecular, and cellular bases of QT-interval prolongation and torsade de pointes. Europace 9(suppl 4):iv4–iv15

    Article  Google Scholar 

  4. Antzelevitch C (2010) M cells in the human heart. Circ Res 106(5):815–817

    Article  Google Scholar 

  5. Antzelevitch C, Sicouri S, Litovsky SH, Lukas A, Krishnan SC, Di Diego JM, Gintant GA, Liu DW (1991) Heterogeneity within the ventricular wall. Circ Res 69(6):1427–1449

    Article  Google Scholar 

  6. Boulaksil M, Jungschleger JG, Antoons G, Houtman MJ, de Boer TP, Wilders R, Beekman JD, Maessen JG, van der Hulst FF, van der Heyden MA, et al (2011) Drug-induced torsade de pointes arrhythmias in the chronic AV block dog are perpetuated by focal activity. Circulation: Arrhythmia Electrophysiol 4(4):566–576

    Google Scholar 

  7. Chang PC, Wo HT, Lee HL, Lin SF, Wen MS, Chu Y, Yeh SJ, Chou CC (2015) Role of sarcoplasmic reticulum calcium in development of secondary calcium rise and early afterdepolarizations in long QT syndrome rabbit model. PLoS ONE 10(4):e0123868

    Article  Google Scholar 

  8. Dunnink A, van Opstal JM, Oosterho P, Winckels SK, Beekman JD, van der Nagel R, Verduyn SC, Vos MA (2012) Ventricular remodelling is a pre-requisite for the induction of dofetilide-induced torsade de pointes arrhythmias in the anaesthetized, complete atrio-ventricular-block dog. Europace 14(3):431–436

    Article  Google Scholar 

  9. Gima K, Rudy Y (2002) Ionic current basis of electrocardiographic waveforms a model study. Circ Res 90(8):889–896

    Article  Google Scholar 

  10. Glukhov AV, Fedorov VV, Lou Q, Ravikumar VK, Kalish PW, Schuessler RB, Moazami N, Efimov IR (2010) Transmural dispersion of repolarization in failing and nonfailing human ventricle. Circ Res 106(5):981–991

    Article  Google Scholar 

  11. Kannankeril P, Roden DM, Darbar D (2010) Drug-induced long QT syndrome. Pharmacol Rev 62(4):760–781

    Article  Google Scholar 

  12. Nattel S, Antzelevitch C, Noble D (2011) Resolving the m-cell debate: why and how. Heart Rhythm: Official J Heart Rhythm Soc 8(8):1293

    Article  Google Scholar 

  13. Noda T, Shimizu W, Satomi K, Suyama K, Kurita T, Aihara N, Kamakura S (2004) Classification and mechanism of Torsade de Pointes initiation in patients with congenital long QT syndrome. Eur Heart J 25(23):2149–2154

    Article  Google Scholar 

  14. Priya PK, Reddy MR (2017) Study of factors affecting the progression and termination of drug induced torsade de pointes in two dimensional cardiac tissue. J Electrocardiol 50(3):332–341

    Article  Google Scholar 

  15. Rush S, Larsen H (1978) A practical algorithm for solving dynamic membrane equations. IEEE Trans Biomed Eng 25(4):389–392

    Article  Google Scholar 

  16. Shiferaw Y, Aistrup GL, Wasserstrom JA (2012) Intracellular Ca2+ waves, afterde-polarizations, and triggered arrhythmias. Cardiovasc Res 95(3):265–268

    Article  Google Scholar 

  17. Ten Tusscher KH, Panfilov AV (2006) Alternans and spiral breakup in a human ventricular tissue model. Am J Physiol-Heart Circulatory Physiol 291(3):H1088–H1100

    Article  Google Scholar 

  18. Vandersickel N, Boer TP, Vos MA, Panfilov AV (2016) Perpetuation of torsade de pointes in heterogeneous hearts: competing foci or re-entry? J Physiol 594(4):6865–6878

    Article  Google Scholar 

  19. Viswanathan PC, Rudy Y (1999) Pause induced early afterdepolarizations in the long QT syndrome: a simulation study. Cardiovasc Res 42(2):530–542

    Article  Google Scholar 

  20. Volders PG, Vos MA, Szabo B, Sipido KR, de Groot SM, Gorgels AP, Wellens HJ, Lazzara R (2000) Progress in the understanding of cardiac early afterdepolarizations and torsades de pointes: time to revise current concepts. Cardiovasc Res 46(3):376–392

    Article  Google Scholar 

  21. Weiss JN, Garfinkel A, Karagueuzian HS, Chen PS, Qu Z (2010) Early afterdepolarizations and cardiac arrhythmias. Heart Rhythm 7(12):1891–1899

    Article  Google Scholar 

  22. Zeng J, Rudy Y (1995) Early afterdepolarizations in cardiac myocytes: mechanism and rate dependence. Biophys J 68(3):949

    Article  Google Scholar 

  23. Zhu TG, Patel C, Martin S, Quan X, Wu Y, Burke JF, Chernick M, Kowey PR, Yan GX (2009) Ventricular transmural repolarization sequence: its relationship with ventricular relaxation and role in ventricular diastolic function. European Heart J 30(3):372–380

    Article  Google Scholar 

Download references

Acknowledgements

This work was funded by the Indian Institute of Technology Madras.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ponnuraj Kirthi Priya .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Kirthi Priya, P., Reddy, M.R. (2019). Study of Polymorphic Ventricular Tachycardia in a 2D Cardiac Transmural Tissue. In: Gulyás, B., Padmanabhan, P., Fred, A., Kumar, T., Kumar, S. (eds) ICTMI 2017. Springer, Singapore. https://doi.org/10.1007/978-981-13-1477-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-1477-3_6

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-1476-6

  • Online ISBN: 978-981-13-1477-3

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics