Hypertrophy in Rat Virtual Left Ventricular Cells and Tissue

  • S. Kharche
  • H. Zhang
  • R. C. Clayton
  • Arun V. Holden
Part of the Lecture Notes in Computer Science book series (LNCS, volume 3504)

Abstract

Left ventricular hypertrophy induces remodeling of various ion channels and prolongs depolarization of the ventricles. We modified a model of electrical activity of rat ventricular cell by incorporating available experimental data. Hypertrophy was modeled by incorporating experimental data of changes in sodium (INa), hyperpolarizing (If), outward transient potassium (Ito) and T-type calcium currents channel kinetics (ICaT), cell size and Ca2 +  handling. In 1D simulations, a continuous increase in action potential duration (APD) and corresponding decrease in conduction velocity (CV) with subsequent beats was observed, resulting in conduction block at low values of stimulus intervals (SI), for which the simulated action potential (AP) restitution of the cell models has negative slope.

Keywords

Action Potential Duration Conduction Block Stimulus Interval Ventricular Cell Transient Outward Current 
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.
    Panfilov, A.V., Zemlin, C.W.: Wave propagation in an excitable medium with a negatively sloped restitution curve. Chaos 12(3), 800–806 (2002)CrossRefGoogle Scholar
  2. 2.
    Pandit, S.V., Clark, R.B., Giles, W.Y., Demir, S.S.: A mathematical model of action potential heterogeneity in adult rat ventricular myocytes. Biophysical Journal 81, 3029–3051 (2001)CrossRefGoogle Scholar
  3. 3.
    Linz, K.W., Meyer, R.: Profile and kinetics of L-type calcium current during the cardiac ventricular action potential compared in guinea-pigs, rats and rabbits. Pflugers Arch. - Eur. J. Physiol. 439, 588–599 (2000)CrossRefGoogle Scholar
  4. 4.
    Li, Q., Keung, E.C.: Effects of myocardial hypertrophy on transient outward current. Am. J. Physiol. 266, H1738–H1745 (1994)Google Scholar
  5. 5.
    Alvarez, J.L., Aimond, F., Lorente, P., Vassort, G.: Late post-myocardial infraction induces a tetrodotoxin-resistant Na +  current in rat myocytes. J. Mol. Cell. Cardiol. 32(7), 1169–1179 (2000)CrossRefGoogle Scholar
  6. 6.
    Zhang, H., Holden, A.V., Kodama, I., Honjo, H., Lei, M.: Mathematical models of action potentials in the periphery of and centre of the rabbit sinoatrial node. Am. J. Physiol. 279, H397–H421 (2000)Google Scholar
  7. 7.
    Winslow, R.L., Rice, J., Jafri, S., Marban, E., O’Rourke, B.: Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure II. Model studies. Circ. Res. 84, 571–586 (1999)Google Scholar
  8. 8.
    Padmala, S., Demir, S.S.: Computational Model of the Ventricular Action Potential in Adult Spontaneously Hypertensive rats. Journal of Cardiovasc. Electrophysiol. 14(9), 990 (2003)CrossRefGoogle Scholar
  9. 9.
    Fernandez-Velasco, M., Goren, N., Benito, G., Blanco-Rivero, J., Bosca, L., Delgado, C.: Regional distribution of hyperpolarization-activated current (If) and hyperpolarization-activated cyclic nucleotide-gated channel mRNA expression in ventricular cells from control and hypertrophied rat hearts. J. Physiol. Lond. 553, 395–405 (2003)CrossRefGoogle Scholar
  10. 10.
    Gomez, A.M., Schwaller, B., Porzig, H., Vassort, G., Niggli, E., Eger, M.: Increased exchange current but normal Ca2 +  transport via INaCa exchange during cardiac hypertrophy after myocardial infraction. Circ. Res. 91, 323–330 (2002)CrossRefGoogle Scholar
  11. 11.
    Yokoshiki, H., Kohya, T., Tomita, F., Tohse, N., Nakaya, N., Kanno, M., Kitabatake, A.: Restoration of action potential duration and transient outward current by regression of left ventricular hypertrophy. J. Mol. Cell. Cardiol. 29, 1331–1339 (1997)CrossRefGoogle Scholar
  12. 12.
    Qin, D., Zhang, Z., Caref, E.B., Boutjdir, M., Jain, P., El-Sherif, N.: Cellular and Ionic Basis of Arrhythmias in Postinfarction Remodeled Ventricular Myocardium. Circ. Res. 79(3), 461–473 (1996)Google Scholar
  13. 13.
    Izumi, T., Kihara, Y., Sarai, N., Yoneda, T., Iwanaga, Y., Inagaki, K.: Reinduction of T-Type Calcium Channels by Endothelin-1 in Failing Hearts In Vivo and in Adult Rat Ventricular Cells. Circulation 108(20), 2530–2535 (2003)CrossRefGoogle Scholar
  14. 14.
    Dokos, S., Celler, B., Lovell, N.: Vagal Control of Sinoatrial Rhythm: a Mathematical Model. Journal of Theoretical Biology 182(1), 21–44 (1996)CrossRefGoogle Scholar
  15. 15.
    Arta, Y., Geshi, E., Nomizo, A., Aoki, S., Katagiri, T.: Alterations in sarcoplasmic reticulum and angiotensin II receptor type I gene expression in spontaneously hypertensive rat hearts. Jpn. Circ. J. 63, 367–372 (1999)CrossRefGoogle Scholar
  16. 16.
    Ward, C.A., Ma, Z., Lee, S.S., Giles, W.R.: Potassium currents in atrial and ventricular myocytes from a rat model of cirrhosis. Am. J. Physiol. 273, G537–G544 (1997)Google Scholar
  17. 17.
    Meiry, G., Reisner, Y., Feld, Y., Goldberg, S., Rosen, M., Ziv, N., Binah, O.: Evolution of action potential propagation and repolarisation in cultured neonatal rat ventricular myocytes. J. Cardiovasc. Electrophysiol. 12(11), 1269–1277 (2001)CrossRefGoogle Scholar
  18. 18.
    Nanasi, P.P., Pankucsi, C., Banyasz, T., Szigligeti, P., Papp, J.G., Varro, A.: Electrical restitution in rat ventricular muscle. Acta Physiol. Scand. 158(2), 143–153 (1996)CrossRefGoogle Scholar
  19. 19.
    Shimoni, Y., Firek, L., Severson, D., Giles, W.R.: Short-term diabetes alters K +  currents in rat ventricular myocytes. Circ. Res. 74, 620–628 (1994)Google Scholar
  20. 20.
    Cerbai, E., Barbieri, M., Li, Q., Mugeli, A.: Occurence and properties of the hyperpolarization activated current If in ventricular myocytes from normotensive and hypertensive rats during aging. Circulation 94, 1674–1681 (1996)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • S. Kharche
    • 1
  • H. Zhang
    • 2
  • R. C. Clayton
    • 3
  • Arun V. Holden
    • 1
  1. 1.Computational Biology Laboratory, School of Biomedical SciencesUniversity of LeedsLeedsUK
  2. 2.Department of PhysicsUMISTManchesterUK
  3. 3.Department of ComputingUniversity of SheffieldSheffieldUK

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