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Ectopic Activity in Ventricular Cells Induced by Early Afterdepolarizations Developed in Purkinje Cells

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Abstract

The development of early afterdepolarizations (EADs) in Purkinje fibers and their propagation to ventricular muscle cells are studied by computer modeling. The Purkinje-ventricular system has been simulated by a two-dimensional model of a Purkinje fiber (PF) connected to a thin sheet of ventricular muscle tissue (VMT). EADs are induced in the PF by enhancing the fast second inward current, i Ca,f and blocking the delayed K+ current, i K while the VMT is kept under physiological conditions. Different phenomena are observed depending on the EAD conditions applied. For 70% i K blockade and i Ca,f enhancement greater than 60%, a single phase 3 EAD developed in the PF propagates to the VMT generating an ectopic beat. For 80% i K blockade and i Ca,f enhancement in the range from 0% to 70%, multiple ectopic beats appear in the VMT. However, for i K blockades over 80%, action potentials in PF cells do not repolarize and the ectopic activity in the VMT disappears. In our simulations, the ionic mechanism underlying phase 3 EAD development is the reactivation of the fast sodium current in the PF. Our results demonstrate that there exists a critical range of EAD conditions that favor the development of EADs in the PF and their propagation to the VMT as ectopic activity. This phenomenon could underlie the genesis of some triggered arrhythmias. © 2000 Biomedical Engineering Society.

PAC00: 8719Nn, 8716Uv, 8719Hh, 8719Ff, 8717Nn

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REFERENCES

  1. Balser, J. R., and D. M. Roden. Inhibitor effect of ventricular muscle on induction of early afterdepolarizations in canine false tendons. Clin. Res 35:260A, 1987.

    Google Scholar 

  2. Berenfeld, O., and J. Jalife. Purkinje-muscle reentry as a mechanism of polymorphic ventricular arrhythmias in a 3-dimensional model of the ventricles. Circ. Res. 82:1063-1077, 1998.

    Google Scholar 

  3. Cabo, C., and R. C. Barr. Unidirectional block in a computer model of partially coupled segments of cardiac Purkinje tissue. Ann. Biomed. Eng. 21:633-644, 1993.

    Google Scholar 

  4. Cartee, L. A., and R. Plonsey, Active response of a one-dimensional cardiac model with gap junctions to extracellular stimulation. Med. Biol. Eng. Comput. 30:389-398, 1992.

    Google Scholar 

  5. Coulombe, A., E. Coraboeuf, C. Malecot, and E. Deroubaix. Role of the Na window current and other ionic currents in triggering early after-depolarizations and resulting re-excitations in Purkinje fibers. In: Cardiac Electrophysiology and Arrhythmias, edited by D. P. Zipes, and J. Jalife. Orlando: Grune and Stratton, 1985, pp. 43-49.

    Google Scholar 

  6. Cranefield, P. F., and R. S. Aronson. Cardiac arrhythmias: the role of triggered activity and other mechanims. New York: Futura, 1988.

    Google Scholar 

  7. DiFrancesco, D., and D. Noble. A model of cardiac electrical activity incorporating ionic pumps and concentration changes. Philos. Trans. R. Soc. London, Ser. B 307:353-398, 1985.

    Google Scholar 

  8. El-Sherif, N. Early afterdepolarizations and arrhythmogenesis. Experimental and clinical aspects. Arch. Mal. Coeur Vaiss 84:227-234, 1991.

    Google Scholar 

  9. El-Sheriff, N., R. H. Zeiler, W. Craelius, W. B. Gough, and R. Henkin. QTU prolongation and polymorphic ventricular tachyarrhythmias due to bradycardia-dependent early afterdepolarizations. Afterdepolarizations and ventricular arrhythmias. Circ. Res. 63:286-305, 1988.

    Google Scholar 

  10. Gibb, W. J., M. B. Wagner, and M. D. Lesh. Effects of simulated potassium blockade on the dynamics of triggered cardiac activity. J. Theor. Biol. 168:245-257, 1994.

    Google Scholar 

  11. Gibb, W. J., M. B. Wagner, and M. D. Lesh. Modeling triggered cardiac activity: an analysis of the interactions between potassium blockade, rhythm pauses, and cellular coupling. Math. Biosci. 137:101-133, 1996.

    Google Scholar 

  12. Huelsing, D. J., K. W. Spitzer, J. M. Cordeiro, and A. E. Pollard. Modulation of repolarization in rabbit Purkinje and ventricular myocytes coupled by a variable resistance. Am. J. Physiol. 276:H572-H581, 1999.

    Google Scholar 

  13. January, C. T., and J. M. Riddle. Early afterdepolarizations: mechanisms of induction and block. A role for L-type Ca 21 current. Circ. Res. 64:977-990, 1989.

    Google Scholar 

  14. January, C. T., J. M. Riddle, and J. J. Salata. A model of early afterdepolarizations: induction with the Ca21 channel agonist Bay K 8644. Circ. Res. 62:563-571, 1988.

    Google Scholar 

  15. Joyner, R. W., E. D. Overholt, B. Ramza, and R. D. Veenstra. Propagation through electrically coupled cells: two in-homogeneously coupled cardiac tissue layers. Am. J. Physiol. 247:H596-H609, 1984.

    Google Scholar 

  16. Jurkiewicz, N. K., and M. C. Sanguinetti. Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent. Circ. Res. 72:75-83, 1993.

    Google Scholar 

  17. Kumar, R., and R. W. Joyner. An experimental model of the production of early after depolarizations by injury current from an ischemic region. Pflügers Arch. 428:425-432, 1994.

    Google Scholar 

  18. Kupersmith, J., Z.-Y. Li, and C. Maldonado. Marked action potential prolongation as a source of injury current leading to border zone arrhythmogenesis. Am. Heart J. 127:1543-1553, 1994.

    Google Scholar 

  19. Lee, K. S., and E. W. Lee. Membrane activity of class III antiarrhythmic compounds; a comparison between ibutilide, d-sotalol, E-4031, sematilide and dofetilide. Eur. J. Pharma-col. 234:43-53, 1993.

    Google Scholar 

  20. Li, Z.-Y., C. Maldonado, C. Zee-Cheng, S. Hiromasa, and J. Kupersmith, Purkinje fibre-papillary muscle interaction in the genesis of triggered activity in a guinea pig model. Cardiovasc. Res. 26:543-548, 1992.

    Google Scholar 

  21. Luo, C. H., and Y. A. Rudy. A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Circ. Res. 74:1071-1096, 1994.

    Google Scholar 

  22. Maldonado, C., Z.-Y. Li, W. B. Wead, T. Szabo, and J. Kupersmith. Mechanisms of triggered activity induction at the border zone of normal and abnormal cardiac tissue. J. Electrocardiol. 29:309-318, 1996.

    Google Scholar 

  23. Méndez, C., and M. Delmar. Triggered activity: its possible role in cardiac arrhythmias. In: Cardiac Electrophysiology and Arrhythmias, edited by D. P. Zipes and J. Jalife. Orlando: Grune and Stratton, 1985, pp. 311-313.

    Google Scholar 

  24. Mendez, C., W. J. Mueller, and X. Urguiaga. Propagation of impulses across the Purkinje fiber-muscle junctions in the dog heart. Circ. Res. 26:135-150, 1970.

    Google Scholar 

  25. Nordin, C. Computer model of electrophysiological instability in very small heterogeneous ventricular syncytia. Am. J. Physiol. 272:H1838-H1856, 1997.

    Google Scholar 

  26. Nordin, C. Computer modeling of interactions between normal and damaged myocytes: new approaches to the etiology of ventricular arrhythmias. Proceedings of the IFAC Sympo-sium, 1994, pp. 70-75.

  27. Oosthoek, P. W., S. Virágh, W. H. Lamers, and A. F. M. Moorman. Immunohistochemical delineation of the conduction system II: The atrioventricular node and Purkinje fibers. Circ. Res. 73:482-491, 1993.

    Google Scholar 

  28. Patterson, E., B. J. Scherlag, and R. Lazzara. Early afterdepolarizations produced by d, l-Sotalol and Clofilium. J. Cardiovasc. Electrophysiol. 8:667-678, 1997.

    Google Scholar 

  29. Pollard, A. E., and R. C. Barr. Computer simulations of activation in an anatomically based model of the human ventricular conduction system. IEEE Trans. Biomed. Eng. 38:982-996, 1991.

    Google Scholar 

  30. Priori, S. G., and P. B. Corr. Mechanisms underlying early and delayed afterdepolarizations induced by catecholamines. Am. J. Physiol. 258:H1796-1805, 1990.

    Google Scholar 

  31. Rawling, D. A., and R. W. Joyner. Characteristics of junctional regions between purkinje and ventricular muscle cells of canine ventricular subendocardium. Circ. Res. 60:580-585, 1987.

    Google Scholar 

  32. Saiz, J., J. M. Ferrero, Jr., M. Monserrat, J. M. Ferrero, and N. V. Thakor. Influence of electrical coupling on early afterdepolarizations in ventricular myocytes. IEEE Trans. Biomed. Eng. 46:138-147, 1999.

    Google Scholar 

  33. Shaw, R. M., and Y. Rudy. Electrophysiologic effects of acute myocardial ischemia. A mechanistic investigation of Action Potential conduction and conduction failure. Circ. Res. 80:124-138, 1997.

    Google Scholar 

  34. Shaw, R. M., and Y. Rudy. Ionic mechanisms of propagation in cardiac tissue. Roles of the sodium and L-type calcium currents during reduced excitability and decreased gap junction coupling. Circ. Res. 81:727-741, 1997.

    Google Scholar 

  35. Szabo, B., T. Kovacs, and R. Lazzara. Role of calcium loading in early afterdepolarizations generated by Cs 1 in canine and guinea pig Purkinje fibers. J. Cardiovasc. Electrophysiol. 6:796-812, 1995.

    Google Scholar 

  36. Szabo, B., R. Sweidan, C. V. Rajagopalan, and R. Lazzara. Role of Na+:Ca2+ exchange current in Cs+-induced early afterdepolarizations in Purkinje fibers. J. Cardiovasc. Elec-trophysiol. 5:933-944, 1994.

    Google Scholar 

  37. Tranum-Jensen, J., A. A. M. Wilde, J. T. Vermeulen, and M. J. Janse. Morphology of electrophysiologically identified junctions between purkinje fibers and ventricular muscle in rabbit and pig hearts. Circ. Res. 69:429-437, 1991.

    Google Scholar 

  38. Veenstra, R. D., R. W. Joyner, and D. A. Rawling. Purkinje and ventricular activation sequences of canine papillary muscle. Effects of quinidine and calcium on the Purkinje-ventricular conduction delay. Circ. Res. 54:500-515, 1984.

    Google Scholar 

  39. Wagner, M. B., W. J. Gibb, and M. D. Lesh. A model study of propagation of early afterdepolarizations. IEEE Trans. Biomed. Eng. 42:991-997, 1995.

    Google Scholar 

  40. Zeng, J., K. R. Laurita, D. S. Rosenbaum, and Y. Rudy. Two components of the delayed rectifier K1 current in ventricular myocytes of the guinea pig type. Theoretical formulation and their role in repolarization. Circ. Res. 77:140-152, 1995.

    Google Scholar 

  41. Zeng, J., and Y. Rudy. Early afterdepolarizations in cardiac myocytes: mechanism and rate dependence. Biophys. J. 68:949-964, 1995.

    Google Scholar 

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Monserrat, M., Saiz, J., Ferrero, J.M. et al. Ectopic Activity in Ventricular Cells Induced by Early Afterdepolarizations Developed in Purkinje Cells. Annals of Biomedical Engineering 28, 1343–1351 (2000). https://doi.org/10.1114/1.1326032

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