(Circulation. 1998;98:1928-1936.)
© 1998 American Heart Association, Inc.
Basic Science Reports |
Cellular Basis for the Normal T Wave and the Electrocardiographic Manifestations of the Long-QT Syndrome
From the Masonic Medical Research Laboratory, Utica, NY.
Correspondence to Dr Charles Antzelevitch, Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501. E-mail ca{at}mmrl.edu
Background—This study probes the cellular basis for the T wave under baseline and long-QT (LQT) conditions using an arterially perfused canine left ventricular (LV) wedge preparation, which permits direct temporal correlation of cellular transmembrane and ECG events.
Methods and Results—Floating microelectrodes were used to record transmembrane action potentials (APs) simultaneously from epicardial, M-region, and endocardial sites or subendocardial Purkinje fibers. A transmural ECG was recorded concurrently. Under baseline and LQT conditions, repolarization of the epicardial action potential, the earliest to repolarize, coincided with the peak of the T wave; repolarization of the M cells, the last to repolarize, coincided with the end of the T wave. Thus, the action potential duration (APD) of the longest M cells determine the QT interval and the Tpeak–Tend interval serves as an index of transmural dispersion of repolarization. Repolarization of Purkinje fibers outlasted that of the M cell but failed to register on the ECG. The morphology of the T wave appeared to be due to currents flowing down voltage gradients on either side of the M region during phase 2 and phase 3 of the ventricular action potential. The interplay between these opposing forces determined the height of the T wave as well as the degree to which the ascending or descending limb of the T wave was interrupted, giving rise to bifurcated T waves and "apparent T-U complexes" under LQT conditions. Spontaneous and stimulation-induced polymorphic ventricular tachycardia with characteristics of torsade de pointes (TdP) developed in the presence of dl-sotalol.
Conclusions—Our results provide the first direct evidence that opposing voltage gradients between epicardium and the M region and endocardium and the M region contribute prominently to the inscription of the ECG T wave under normal conditions and to the widened or bifurcated T wave and long-QT interval observed under LQT conditions. Our data suggest that the "pathophysiological U" wave observed in acquired or congenital LQTS is more likely to be a second component of an interrupted T wave, and argue for use of the term T2 in place of U to describe this event.
Key Words: cells • electrophysiology • waves • action potentials • electrocardiography • long-QT syndrome
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K. Takenaka, T. Ai, W. Shimizu, A. Kobori, T. Ninomiya, H. Otani, T. Kubota, H. Takaki, S. Kamakura, and M. Horie Exercise Stress Test Amplifies Genotype-Phenotype Correlation in the LQT1 and LQT2 Forms of the Long-QT Syndrome Circulation, February 18, 2003; 107(6): 838 - 844. [Abstract] [Full Text] [PDF]
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V. A. Medina-Ravell, R. S. Lankipalli, G.-X. Yan, C. Antzelevitch, N. A. Medina-Malpica, O. A. Medina-Malpica, C. Droogan, and P. R. Kowey Effect of Epicardial or Biventricular Pacing to Prolong QT Interval and Increase Transmural Dispersion of Repolarization: Does Resynchronization Therapy Pose a Risk for Patients Predisposed to Long QT or Torsade de Pointes? Circulation, February 11, 2003; 107(5): 740 - 746. [Abstract] [Full Text] [PDF]
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 J. Nemec, J. B. Hejlik, W.-K. Shen, and M. J. Ackerman Catecholamine-Induced T-Wave Lability in Congenital Long QT Syndrome: A Novel Phenomenon Associated With Syncope and Cardiac Arrest Mayo Clin. Proc., January 1, 2003; 78(1): 40 - 50. [Abstract] [PDF]
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M. Viitasalo, L. Oikarinen, H. Swan, H. Vaananen, K. Glatter, P. J. Laitinen, K. Kontula, H. V. Barron, L. Toivonen, and M. M. Scheinman Ambulatory Electrocardiographic Evidence of Transmural Dispersion of Repolarization in Patients With Long-QT Syndrome Type 1 and 2 Circulation, November 5, 2002; 106(19): 2473 - 2478. [Abstract] [Full Text] [PDF]
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J. M. Di Diego, J. M. Cordeiro, R. J. Goodrow, J. M. Fish, A. C. Zygmunt, G. J. Perez, F. S. Scornik, and C. Antzelevitch Ionic and Cellular Basis for the Predominance of the Brugada Syndrome Phenotype in Males Circulation, October 8, 2002; 106(15): 2004 - 2011. [Abstract] [Full Text] [PDF]
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E. Pietila, H. Fodstad, E. Niskasaari, P.a. J. Laitinen, H. Swan, M. Savolainen, Y. A. Kesaniemi, K. Kontula, and H. V. Huikuri association between HERG K897T polymorphism and QT interval in middle-aged finnish women J. Am. Coll. Cardiol., August 7, 2002; 40(3): 511 - 514. [Abstract] [Full Text] [PDF]
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C. Antzelevitch Sympathetic modulation of the long QT syndrome Eur. Heart J., August 2, 2002; 23(16): 1246 - 1252. [PDF]
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W. Shimizu, Y. Tanabe, T. Aiba, M. Inagaki, T. Kurita, K. Suyama, N. Nagaya, A. Taguchi, N. Aihara, K. Sunagawa, et al. Differential effects of beta-blockade on dispersion of repolarization in the absence and presence of sympathetic stimulation between the lqt1 and lqt2 forms of congenital long qt syndrome J. Am. Coll. Cardiol., June 19, 2002; 39(12): 1984 - 1991. [Abstract] [Full Text] [PDF]
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K. Gima and Y. Rudy Ionic Current Basis of Electrocardiographic Waveforms: A Model Study Circ. Res., May 3, 2002; 90(8): 889 - 896. [Abstract] [Full Text] [PDF]
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 D. Noble Modeling the Heart--from Genes to Cells to the Whole Organ Science, March 1, 2002; 295(5560): 1678 - 1682. [Abstract] [Full Text] [PDF]
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J. Wu, J. Wu, and D. P. Zipes Early Afterdepolarizations, U Waves, and Torsades de Pointes Circulation, February 12, 2002; 105(6): 675 - 676. [Full Text] [PDF]
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G.-X. Yan, S. J. Rials, Y. Wu, T. Liu, X. Xu, R. A. Marinchak, and P. R. Kowey Ventricular hypertrophy amplifies transmural repolarization dispersion and induces early afterdepolarization Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1968 - H1975. [Abstract] [Full Text] [PDF]
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D. di Bernardo, A. Murray, A. A.M. Wilde, and D. M. Roden T-Wave Shape in Clinical Research Response Circulation, October 9, 2001; 104 (15): e80 - e80. [Full Text] [PDF]
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J. E. Burnes, R. N. Ghanem, A. L. Waldo, and Y. Rudy Imaging Dispersion of Myocardial Repolarization, I: Comparison of Body-Surface and Epicardial Measures Circulation, September 11, 2001; 104(11): 1299 - 1305. [Abstract] [Full Text] [PDF]
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M. Johansson and L. Carlsson Female Gender Does Not Influence the Magnitude of Ibutilide-Induced Repolarization Delay and Incidence of Torsades de Pointes in an In Vivo Rabbit Model of the Acquired Long QT Syndrome Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2001; 6(3): 247 - 254. [Abstract] [PDF]
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 C. Antzelevitch Heterogeneity of cellular repolarization in LQTS: the role of M cells Eur. Heart J. Suppl., September 1, 2001; 3(suppl_K): K2 - K16. [Abstract] [PDF]
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A. C. Zygmunt, G. T. Eddlestone, G. P. Thomas, V. V. Nesterenko, and C. Antzelevitch Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H689 - H697. [Abstract] [Full Text] [PDF]
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G.-X. Yan, Y. Wu, T. Liu, J. Wang, R. A. Marinchak, and P. R. Kowey 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, June 12, 2001; 103(23): 2851 - 2856. [Abstract] [Full Text] [PDF]
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C. Antzelevitch Transmural dispersion of repolarization and the T wave Cardiovasc Res, June 1, 2001; 50(3): 426 - 431. [Full Text] [PDF]
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 B. Rosati, Z. Pan, S. Lypen, H.-S. Wang, I. Cohen, J. E Dixon, and D. McKinnon Regulation of KChIP2 potassium channel {beta} subunit gene expression underlies the gradient of transient outward current in canine and human ventricle J. Physiol., May 15, 2001; 533(1): 119 - 125. [Abstract] [Full Text] [PDF]
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