© 1996 American Heart Association, Inc.
Articles |
The Electrophysiological Mechanism of Ventricular Arrhythmias in the Long QT Syndrome
Tridimensional Mapping of Activation and Recovery Patterns
the Cardiology Division, Department of Medicine, State University of New York Health Science Center and Veterans Affairs Medical Center, Brooklyn.
We have previously developed a canine in vivo model of the long QT syndrome (LQTS) using the neurotoxin anthopleurin A (AP-A), which acts by slowing sodium channel inactivation. The recent discovery of a genetic mutation in the cardiac sodium channel in some patients with the congenital LQTS, resulting in abnormal gating behavior similar to sodium channels exposed to AP-A, provides a strong endorsement of this animal model as a valid surrogate to the clinical syndrome of LQTS. In the present study, we conducted high-resolution tridimensional isochronal mapping of both activation and repolarization patterns in puppies exposed to AP-A that developed LQTS and polymorphic ventricular tachyarrhythmias (VTs). To map repolarization, we measured activation-recovery intervals (ARIs) using multiple unipolar extracellular electrograms. We demonstrated, for the first time in vivo, the existence of spatial dispersion of repolarization in the ventricular wall and differences in regional recovery in response to cycle-length changes that were markedly exaggerated after AP-A administration. Analysis of tridimensional activation patterns showed that the initial beat of polymorphic VT consistently arose as focal activity from a subendocardial site, whereas subsequent beats were due to successive subendocardial focal activity, reentrant excitation, or a combination of both mechanisms. Reentrant excitation was due to infringement of a focal activity on the spatial dispersion of repolarization, resulting in functional conduction block and circulating wave fronts. The polymorphic QRS configuration of VT in the LQTS was due to either changing the site of origin of focal activity, resulting in varying activation patterns, or varying orientations of circulating wave fronts.
Key Words: arrhythmia • ventricular tachycardia • mapping • reentry • early afterdepolarization
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D. Lacroix, F. Extramiana, P. Delfaut, M. Adamantidis, D. Grandmougin, D. Klug, S. Kacet, and B. Dupuis Factors affecting epicardial dispersion of repolarization: a mapping study in the isolated porcine heart Cardiovasc Res, March 1, 1999; 41(3): 563 - 574. [Abstract] [Full Text] [PDF]
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E. Robert, A. G. M. Aya, J. E. de la Coussaye, P. Peray, J.-M. Juan, J. Brugada, J.-M. Davy, and J.-J. Eledjam Dispersion-based reentry: mechanism of initiation of ventricular tachycardia in isolated rabbit hearts Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H413 - H423. [Abstract] [Full Text] [PDF]
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S. M. Pogwizd, J. P. McKenzie, and M. E. Cain Mechanisms Underlying Spontaneous and Induced Ventricular Arrhythmias in Patients With Idiopathic Dilated Cardiomyopathy Circulation, December 1, 1998; 98(22): 2404 - 2414. [Abstract] [Full Text] [PDF]
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W. Shimizu and C. Antzelevitch Cellular Basis for the ECG Features of the LQT1 Form of the Long-QT Syndrome : Effects of ß-Adrenergic Agonists and Antagonists and Sodium Channel Blockers on Transmural Dispersion of Repolarization and Torsade de Pointes Circulation, November 24, 1998; 98(21): 2314 - 2322. [Abstract] [Full Text] [PDF]
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G.-X. Yan, W. Shimizu, and C. Antzelevitch Characteristics and Distribution of M Cells in Arterially Perfused Canine Left Ventricular Wedge Preparations Circulation, November 3, 1998; 98(18): 1921 - 1927. [Abstract] [Full Text] [PDF]
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G.-X. Yan and C. Antzelevitch Cellular Basis for the Normal T Wave and the Electrocardiographic Manifestations of the Long-QT Syndrome Circulation, November 3, 1998; 98(18): 1928 - 1936. [Abstract] [Full Text] [PDF]
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E. Drouin, G. Lande, and F. Charpentier Amiodarone reduces transmural heterogeneity of repolarization in the human heart J. Am. Coll. Cardiol., October 1, 1998; 32(4): 1063 - 1067. [Abstract] [Full Text] [PDF]
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W. Zareba, A. J. Moss, P. J. Schwartz, G. M. Vincent, J. L. Robinson, S. G. Priori, J. Benhorin, E. H. Locati, J. A. Towbin, M. T. Keating, et al. Influence of the Genotype on the Clinical Course of the Long-QT Syndrome N. Engl. J. Med., October 1, 1998; 339(14): 960 - 965. [Abstract] [Full Text] [PDF]
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M. Chinushi, M. Restivo, E. B. Caref, and N. El-Sherif Electrophysiological Basis of Arrhythmogenicity of QT/T Alternans in the Long-QT Syndrome : Tridimensional Analysis of the Kinetics of Cardiac Repolarization Circ. Res., September 21, 1998; 83(6): 614 - 628. [Abstract] [Full Text] [PDF]
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M. A. Vos, S. H. M. de Groot, S. C. Verduyn, J. van der Zande, H. D. M. Leunissen, J. P. M. Cleutjens, M. van Bilsen, M. J. A. P. Daemen, J. J. Schreuder, M. A. Allessie, et al. Enhanced Susceptibility for Acquired Torsade de Pointes Arrhythmias in the Dog With Chronic, Complete AV Block Is Related to Cardiac Hypertrophy and Electrical Remodeling Circulation, September 15, 1998; 98(11): 1125 - 1135. [Abstract] [Full Text] [PDF]
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L. Eckardt, W. Haverkamp, M. Borggrefe, and G. Breithardt Experimental models of torsade de pointes Cardiovasc Res, July 1, 1998; 39(1): 178 - 193. [Abstract] [Full Text] [PDF]
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M. Zabel, T. Klingenheben, M. R. Franz, and S. H. Hohnloser Assessment of QT Dispersion for Prediction of Mortality or Arrhythmic Events After Myocardial Infarction : Results of a Prospective, Long-term Follow-up Study Circulation, June 30, 1998; 97(25): 2543 - 2550. [Abstract] [Full Text] [PDF]
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O. Berenfeld and J. Jalife Purkinje-Muscle Reentry as a Mechanism of Polymorphic Ventricular Arrhythmias in a 3-Dimensional Model of the Ventricles Circ. Res., June 1, 1998; 82(10): 1063 - 1077. [Abstract] [Full Text] [PDF]
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K. Derakhchan, R. Cardinal, S. Brunet, D. Klug, C. Pharand, T. Kus, and B. I. Sasyniuk Polymorphic ventricular tachycardias induced by D-sotalol and phenylephrine in canine preparations of atrioventricular block: initiation in the conduction system followed by spatially unstable re-entry Cardiovasc Res, June 1, 1998; 38(3): 617 - 630. [Abstract] [Full Text] [PDF]
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W. Shimizu, T. Kurita, K. Matsuo, K. Suyama, N. Aihara, S. Kamakura, J. A. Towbin, and K. Shimomura Improvement of Repolarization Abnormalities by a K+ Channel Opener in the LQT1 Form of Congenital Long-QT Syndrome Circulation, April 28, 1998; 97(16): 1581 - 1588. [Abstract] [Full Text] [PDF]
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H. S. Oster, B. Taccardi, R. L. Lux, P. R. Ershler, and Y. Rudy Electrocardiographic Imaging : Noninvasive Characterization of Intramural Myocardial Activation From Inverse-Reconstructed Epicardial Potentials and Electrograms Circulation, April 21, 1998; 97(15): 1496 - 1507. [Abstract] [Full Text] [PDF]
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J. F. Spear and E. N. Moore Modulation of quinidine-induced arrhythmias by temperature in perfused rabbit heart Am J Physiol Heart Circ Physiol, March 1, 1998; 274(3): H817 - H828. [Abstract] [Full Text] [PDF]
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S. Nattel Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs Cardiovasc Res, March 1, 1998; 37(3): 567 - 577. [Abstract] [Full Text] [PDF]
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N. El-Sherif, M. Chinushi, E. B. Caref, and M. Restivo Electrophysiological Mechanism of the Characteristic Electrocardiographic Morphology of Torsade de Pointes Tachyarrhythmias in the Long-QT Syndrome : Detailed Analysis of Ventricular Tridimensional Activation Patterns Circulation, December 16, 1997; 96(12): 4392 - 4399. [Abstract] [Full Text]
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E. P. Anyukhovsky, E. A. Sosunov, S. J. Feinmark, and M. R. Rosen Effects of Quinidine on Repolarization in Canine Epicardium, Midmyocardium, and Endocardium : II. In Vivo Study Circulation, December 2, 1997; 96(11): 4019 - 4026. [Abstract] [Full Text]
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V. A. Maltsev and A. I. Undrovinas Cytoskeleton modulates coupling between availability and activation of cardiac sodium channel Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H1832 - H1840. [Abstract] [Full Text] [PDF]
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