Abstract
The electrophysiological basis underlying the genesis of the U wave remains uncertain. Previous U wave modeling studies have generally been restricted to 1-D or 2-D geometries, and it is not clear whether the U waves generated by these models would match clinically observed U wave body surface potential distributions (BSPDs). We investigated the role of M cells and transmural dispersion of repolarization (TDR) in a 2-D, fully ionic heart tissue slice model and a realistic 3-D heart/torso model. In the 2-D model, while a U wave was present in the ECG with dynamic gap junction conductivity, the ECG with static gap junctions did not exhibit a U wave. In the 3-D model, TDR was necessary to account for the clinically observed potential minimum in the right shoulder area during the U wave peak. Peak T wave simulations were also run. Consistent with at least some clinical findings, the U wave body surface maximum was shifted to the right compared to the T wave maximum. We conclude that TDR can account for the clinically observed U wave BSPD, and that dynamic gap junction conductivity can result in realistic U waves generated by M cells.
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Antzelevitch, C. Modulation of transmural repolarization. Ann. N. Y. Acad. Sci. 1047:314–323, 2005.
Antzelevitch, C., and S. Sicouri. Clinical relevance of cardiac arrhythmias generated by after depolarizations. Role of M cells in the generation of U waves, triggered activity and torsade de pointes. J. Am. Coll. Cardiol. 23(1):259–277, 1994.
Ashikaga, H., B. A. Coppola, B. Hopenfeld, E. S. Leifer, E. R. McVeigh, and J. H. Omens. Transmural dispersion of myofiber mechanics: implications for electrical heterogeneity in vivo. J. Am. Coll. Cardiol. 49(8):909–916, 2007.
Campbell, S. G., S. N. Flaim, C. H. Leem, and A. D. McCulloch. Mechanisms of transmurally varying myocyte electromechanics in an integrated computational model. Philos. Trans. 366(1879):3361–3380, 2008.
Depolli, M., V. Avbelj, and R. Trobec. Computer-simulated alternative modes of U-wave genesis. J. Cardiovasc. Electrophysiol. 19(1):84–89, 2008.
di Bernardo, D., and A. Murray. Computer model for study of cardiac repolarization. J. Cardiovasc. Electrophysiol. 11(8):895–899, 2000.
di Bernardo, D., and A. Murray. Origin on the electrocardiogram of U-waves and abnormal U-wave inversion. Cardiovasc. Res. 53(1):202–208, 2002.
Drouin, E., F. Charpentier, C. Gauthier, K. Laurent, and H. Le Marec. Electrophysiologic characteristics of cells spanning the left ventricular wall of human heart: evidence for presence of M cells. J. Am. Coll. Cardiol. 26(1):185–192, 1995.
Einthoven, W. Le elecardiogramme. Arch. Int. Physiol. 4:132–164, 1906.
Goernig, M., J. Haueisen, M. Liehr, M. Schlosser, H. R. Figulla, and U. Leder. Detection of U wave activity in healthy volunteers by high-resolution magnetocardiography. J. Electrocardiol. 43(1):43–47, 2010.
Hoffman, J. D. The finite element method. In: Numerical Methods for Engineers and Scientists, 2nd ed, edited by J. D. Hoffman. New York: Marcel Dekker, 2001, pp. 711–774.
Hoffman, B. F., and P. F. Cranefield. Electrophysiology of the Heart. New York: McGraw-Hill, 1960.
Hopenfeld, B. ST segment depression: the possible role of global repolarization dynamics. Biomed. Eng. Online 6:6, 2007.
Lepeschkin, E. Physiological basis of the U wave. In: Advances in Electrocardiography, edited by R. C. Schlant, and J. W. Hurst. New York: Grune and Stratton, 1972, pp. 431–447.
Lin, X., J. Gemel, E. C. Beyer, and R. D. Veenstra. Dynamic model for ventricular junctional conductance during the cardiac action potential. Am. J. Physiol. Heart Circ. Physiol. 288(3):H1113–H1123, 2005.
Miller, W. T., and D. B. Geselowitz. Simulation studies of the electrocardiogram. I. The normal heart. Circ. Res. 43(2):301–315, 1978.
Muzikant, A. L., E. W. Hsu, P. D. Wolf, and C. S. Henriquez. Region specific modeling of cardiac muscle: comparison of simulated and experimental potentials. Ann. Biomed. Eng. 30(7):867–883, 2002.
Nesterenko, V. V., and C. Antzelevitch. Simulation of the electrocardiographic U wave in heterogeneous myocardium: effect of local junctional resistance. Proceedings of the Computers in Cardiology. Los Alamitos, CA: IEEE Computer Society Press, pp. 43–46, 1992.
Nielsen, P. M., I. J. Le Grice, B. H. Smaill, and P. J. Hunter. Mathematical model of geometry and fibrous structure of the heart. Am. J. Physiol. 260(4 Pt 2):H1365–H1378, 1991.
Noma, A., and N. Tsuboi. Dependence of junctional conductance on proton, calcium and magnesium ions in cardiac paired cells of guinea pig. J. Physiol. 382:193–211, 1987.
Oka, C., H. Matsuda, N. Sarai, and A. Noma. Modeling the calcium gate of cardiac gap junction channel. J. Physiol. Sci. 56(1):79–85, 2006.
Opthof, T., R. Coronel, and M. J. Janse. Is there a significant transmural gradient in repolarization time in the intact heart? Repolarization gradients in the intact heart. Circ. Arrhythm. Electrophysiol. 2:89–96, 2009.
Ritsema van Eck, H. J., J. A. Kors, and G. van Herpen. The U wave in the electrocardiogram: a solution for a 100-year-old riddle. Cardiovasc. Res. 67(2):256–262, 2005.
Rush, S., and H. Larsen. A practical algorithm for solving dynamic membrane equations. IEEE Trans. Biomed. Eng. 25(4):389–392, 1978.
Schimpf, R., C. Antzelevitch, D. Haghi, C. Giustetto, A. Pizzuti, F. Gaita, C. Veltmann, C. Wolpert, and M. Borggrefe. Electromechanical coupling in patients with the short QT syndrome: further insights into the mechanoelectrical hypothesis of the U wave. Heart Rhythm 5(2):241–245, 2008.
Spach, M. S., and R. C. Barr. Ventricular intramural and epicardial potential distributions during ventricular activation and repolarization in the intact dog. Circ. Res. 37(2):243–257, 1975.
Spach, M. S., R. C. Barr, R. B. Warren, D. W. Benson, A. Walston, and S. B. Edwards. Isopotential body surface mapping in subjects of all ages: emphasis on low-level potentials with analysis of the method. Circulation 59(4):805–821, 1979.
Stinstra, J. G., B. Hopenfeld, and R. S. Macleod. On the passive cardiac conductivity. Ann. Biomed. Eng. 3(12):1743–1751, 2005.
Surawicz, B. U wave: facts, hypotheses, misconceptions, and misnomers. J. Cardiovasc. Electrophysiol. 9(10):1117–1128, 1998.
Taggart, P., P. Sutton, T. Opthof, R. Coronel, and P. Kallis. Electrotonic cancellation of transmural electrical gradients in the left ventricle in man. Prog. Biophys. Mol. Biol. 82(1–3):243–254, 2003.
ten Tusscher, K. H., D. Noble, P. J. Noble, and A. V. Panfilov. A model for human ventricular tissue. Am. J. Physiol. Heart Circ. Physiol. 286(4):H1573–H1589, 2004.
Yan, G. X., and C. Antzelevitch. Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-QT syndrome. Circulation 98(18):1928–1936, 1998.
Acknowledgments
The authors wish to thank Elliot McVeigh, PhD, for financial and spiritual support for this study. This study was supported by grants from the NHLBI (Z01-HL004609 to Elliot R. McVeigh, PhD). This study was made possible in part by the facilities of the NIH/NCRR Center for Integrative Biomedical Computing (P41-RR12553).
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Associate Editor Berj L. Bardakjian oversaw the review of this article.
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Hopenfeld, B., Ashikaga, H. Origin of the Electrocardiographic U Wave: Effects of M Cells and Dynamic Gap Junction Coupling. Ann Biomed Eng 38, 1060–1070 (2010). https://doi.org/10.1007/s10439-010-9941-5
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DOI: https://doi.org/10.1007/s10439-010-9941-5