(Circulation. 1997;96:4027-4035.)
© 1997 American Heart Association, Inc.
Articles |
Functional Mechanisms Underlying Tachycardia-Induced Sustained Atrial Fibrillation in a Chronic Dog Model
From the Department of Medicine and Research Center, Montreal (Quebec) Heart Institute and University of Montreal (R.G., R.F.B., M.T., S.N.), and the Department of Pharmacology and Therapeutics (S.N.), McGill University, Montreal, Quebec, Canada.
Correspondence to Stanley Nattel, MD, Research Center, Montreal Heart Institute, 5000 Bélanger St E, Montreal, Quebec H1T 1C8, Canada. E-mail nattel{at}icm.umontreal.ca.
Background Rapid atrial activation causes electrical remodeling that promotes atrial fibrillation (AF), but underlying mechanisms are incompletely understood. We applied epicardial mapping to evaluate atrial electrophysiology and AF duration in dogs subjected to rapid atrial pacing (400/min).
Methods and Results Dogs paced for 1 (P1, n=7), 7 (P7, n=13), or 42 (P42, n=7) days were compared with sham dogs (P0, n=13). Atrial pacing progressively increased AF duration. Atrial effective refractory period (ERP) and ERP accommodation to rate were significantly decreased by pacing, with near-maximal changes within 7 days. Atrial conduction velocity decreased more slowly, with maximum changes at 42 days, contributing to increases in AF duration after ERP stabilized. Stepwise multilinear regression indicated that both wavelength (P=.02) and duration of pacing (P=.0001) were independent determinants of changes in AF duration. Mean atrial fibrillation cycle length (AFCL) at 112 recording sites decreased with increased duration of rapid pacing (P<.001), and the SD of AFCL increased progressively (P<.0001), together accounting for 72% of the variance in AF duration. Increases in AFCL variability were due to regionally determined differences in AFCL changes caused by rapid pacing. The number of zones of reactivation per cycle of AF increased as AF became more sustained, consistent with multiple-wavelet reentry.
Conclusions Rapid atrial activation causes time-dependent decreases in ERP, conduction velocity, and wavelength, which, along with increased regional heterogeneity, provide a substrate for AF. The conduction abnormalities and increased regional heterogeneity previously noted in patients with AF may be a consequence, as well as a cause, of the tachyarrhythmia.
Key Words: atrial fibrillation • pacing • conduction • electrocardiography • arrhythmia
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J. V. Jayachandran, H. J. Sih, W. Winkle, D. P. Zipes, G. D. Hutchins, and J. E. Olgin Atrial Fibrillation Produced by Prolonged Rapid Atrial Pacing Is Associated With Heterogeneous Changes in Atrial Sympathetic Innervation Circulation, March 14, 2000; 101(10): 1185 - 1191. [Abstract] [Full Text] [PDF]
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H. Ramanna, R. N. W. Hauer, F. H. M. Wittkampf, J. M. T. de Bakker, E. F. D. Wever, A. Elvan, and E. O. Robles de Medina Identification of the Substrate of Atrial Vulnerability in Patients With Idiopathic Atrial Fibrillation Circulation, March 7, 2000; 101(9): 995 - 1001. [Abstract] [Full Text] [PDF]
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S. Fareh, A. Benardeau, B. Thibault, and S. Nattel The T-Type Ca2+ Channel Blocker Mibefradil Prevents the Development of a Substrate for Atrial Fibrillation by Tachycardia-Induced Atrial Remodeling in Dogs Circulation, November 23, 1999; 100(21): 2191 - 2197. [Abstract] [Full Text] [PDF]
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R. F. Bosch, X. Zeng, J. B. Grammer, K. Popovic, C. Mewis, and V. Kuhlkamp Ionic mechanisms of electrical remodeling in human atrial fibrillation Cardiovasc Res, October 1, 1999; 44(1): 121 - 131. [Abstract] [Full Text] [PDF]
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S. Nattel Ionic Determinants of Atrial Fibrillation and Ca2+ Channel Abnormalities : Cause, Consequence, or Innocent Bystander? Circ. Res., September 3, 1999; 85(5): 473 - 476. [Full Text] [PDF]
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D. Li, S. Fareh, T. K. Leung, and S. Nattel Promotion of Atrial Fibrillation by Heart Failure in Dogs : Atrial Remodeling of a Different Sort Circulation, July 6, 1999; 100(1): 87 - 95. [Abstract] [Full Text] [PDF]
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A. M. Gillis, D. G. Wyse, S. J. Connolly, M. Dubuc, F. Philippon, R. Yee, P. Lacombe, M. S. Rose, and C. D. Kerr Atrial Pacing Periablation for Prevention of Paroxysmal Atrial Fibrillation Circulation, May 18, 1999; 99(19): 2553 - 2558. [Abstract] [Full Text] [PDF]
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S. Nattel Atrial electrophysiological remodeling caused by rapid atrial activation: underlying mechanisms and clinical relevance to atrial fibrillation Cardiovasc Res, May 1, 1999; 42(2): 298 - 308. [Abstract] [Full Text] [PDF]
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R. Gaspo, H. Sun, S. Fareh, M. Levi, L. Yue, B. G. Allen, T. E. Hebert, and S. Nattel Dihydropyridine and beta adrenergic receptor binding in dogs with tachycardia-induced atrial fibrillation Cardiovasc Res, May 1, 1999; 42(2): 434 - 442. [Abstract] [Full Text] [PDF]
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W.-C. Yu, S.-H. Lee, C.-T. Tai, C.-F. Tsai, M.-H. Hsieh, C.-C. Chen, Y.-A. Ding, M.-S. Chang, and S.-A. Chen Reversal of atrial electrical remodeling following cardioversion of long-standing atrial fibrillation in man Cardiovasc Res, May 1, 1999; 42(2): 470 - 476. [Abstract] [Full Text] [PDF]
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M. Courtemanche, R. J Ramirez, and S. Nattel Ionic targets for drug therapy and atrial fibrillation-induced electrical remodeling: insights from a mathematical model Cardiovasc Res, May 1, 1999; 42(2): 477 - 489. [Abstract] [Full Text] [PDF]
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L. Yue, P. Melnyk, R. Gaspo, Z. Wang, and S. Nattel Molecular Mechanisms Underlying Ionic Remodeling in a Dog Model of Atrial Fibrillation Circ. Res., April 16, 1999; 84(7): 776 - 784. [Abstract] [Full Text] [PDF]
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L.-P. Lai, M.-J. Su, J.-L. Lin, F.-Y. Lin, C.-H. Tsai, Y.-S. Chen, S. K. S. Huang, Y.-Z. Tseng, and W.-P. Lien Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca2+-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban: An insight into the mechanism of atrial electrical remodeling J. Am. Coll. Cardiol., April 1, 1999; 33(5): 1231 - 1237. [Abstract] [Full Text] [PDF]
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S.-H. Lee, F.-Y. Lin, W.-C. Yu, J.-J. Cheng, P. Kuan, C.-R. Hung, M.-S. Chang, and S.-A. Chen Regional Differences in the Recovery Course of Tachycardia-Induced Changes of Atrial Electrophysiological Properties Circulation, March 9, 1999; 99(9): 1255 - 1264. [Abstract] [Full Text] [PDF]
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S. Fareh, C. Villemaire, and S. Nattel Importance of Refractoriness Heterogeneity in the Enhanced Vulnerability to Atrial Fibrillation Induction Caused by Tachycardia-Induced Atrial Electrical Remodeling Circulation, November 17, 1998; 98(20): 2202 - 2209. [Abstract] [Full Text] [PDF]
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J. Feng, L. Yue, Z. Wang, and S. Nattel Ionic Mechanisms of Regional Action Potential Heterogeneity in the Canine Right Atrium Circ. Res., September 7, 1998; 83(5): 541 - 551. [Abstract] [Full Text] [PDF]
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R. Gaspo, R. F. Bosch, E. Bou-Abboud, and S. Nattel Tachycardia-Induced Changes in Na+ Current in a Chronic Dog Model of Atrial Fibrillation Circ. Res., December 19, 1997; 81(6): 1045 - 1052. [Abstract] [Full Text]
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