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(Circulation. 1996;94:2968-2974.)
© 1996 American Heart Association, Inc.
Articles |
Electrical Remodeling in Atrial Fibrillation
Time Course and Mechanisms
the Carlyle Fraser Heart Center and the Division of Cardiology, Emory University Hospital, Atlanta, Ga.
Background Atrial fibrillation is self-perpetuating, suggesting that the tachyarrhythmia causes electrophysiological changes that contribute to the progressive nature of the disease. In animal models, pacing-induced rapid atrial rates result in sustained atrial fibrillation. This is mediated by shortening of refractory periods termed electrical remodeling. The purpose of the present study was to characterize the time course of electrical remodeling and to define mechanisms of the phenomenon.
Methods and Results Closed-chest dogs were anesthetized, pretreated with atropine and propranolol, and subjected to 7 hours of atrial pacing at 800 bpm. The effective and absolute refractory periods (ARP and ERP) were measured during and after rapid pacing, and transvenous endocardial biopsy specimens were examined using electron microscopy. Despite autonomic blockade and the absence of change in right atrial pressure, persistent atrial tachycardia caused ARP and ERP to fall by >10%. Electrical remodeling developed quickly, with more than half of the phenomenon occurring during the first 30 minutes of high-rate pacing. Pretreatment with glibenclamide in doses sufficient to block the ATP-sensitive potassium current had no effect. Atrial electrical remodeling was blocked by verapamil and accentuated by hypercalcemia. Biopsy specimens from controls subjected to rapid pacing showed mitochondrial swelling consistent with calcium overload. Biopsies from verapamil-treated animals were normal.
Conclusions Atrial electrical remodeling develops quickly, is progressive, and may be persistent. Shifts in autonomic tone, atrial stretch, or depletion of high-energy phosphates do not contribute significantly to the phenomenon. Results of the study suggest that atrial electrical remodeling is mediated by rate-induced intracellular calcium overload.
Key Words: atrium • fibrillation • calcium • electrophysiology
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E. BERTAGLIA, D. D'ESTE, A. ZANOCCO, F. ZERBO, and P. PASCOTTO Effects of pretreatment with verapamil on early recurrences after electrical cardioversion of persistent atrial fibrillation: a randomised study Heart, May 1, 2001; 85(5): 578 - 580. [Full Text]
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M. Vitadello, J. Ausma, M. Borgers, A. Gambino, D. C. Casarotto, and L. Gorza Increased Myocardial GRP94 Amounts During Sustained Atrial Fibrillation : A Protective Response? Circulation, May 1, 2001; 103(17): 2201 - 2206. [Abstract] [Full Text] [PDF]
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R. H. Falk Atrial Fibrillation N. Engl. J. Med., April 5, 2001; 344(14): 1067 - 1078. [Full Text] [PDF]
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C Pandozi and M Santini Update on atrial remodelling owing to rate. Does atrial fibrillation always 'beget' atrial fibrillation? Eur. Heart J., April 1, 2001; 22(7): 541 - 553. [PDF]
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H. Ramanna, A. Elvan, F. H. M. Wittkampf, J. M. T. de Bakker, R. N. W. Hauer, and E. O. Robles de Medina Increased dispersion and shortened refractoriness caused by verapamil in chronic atrial fibrillation J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1403 - 1407. [Abstract] [Full Text] [PDF]
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A. Benardeau, S. Fareh, and S. Nattel Effects of verapamil on atrial fibrillation and its electrophysiological determinants in dogs Cardiovasc Res, April 1, 2001; 50(1): 85 - 96. [Abstract] [Full Text] [PDF]
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 N. R Grubb and S. Furniss Science, medicine, and the future: Radiofrequency ablation for atrial fibrillation BMJ, March 31, 2001; 322(7289): 777 - 780. [Full Text]
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J.-L. Lin, L.-P. Lai, Y.-Z. Tseng, W.-P. Lien, and S. K. S. Huang Global distribution of atrial ectopic foci triggering recurrence of atrial tachyarrhythmia after electrical cardioversion of long-standing atrial fibrillation: a bi-atrial basket mapping study J. Am. Coll. Cardiol., March 1, 2001; 37(3): 904 - 910. [Abstract] [Full Text] [PDF]
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B. J. J. M. Brundel, I. C. Van Gelder, R. H. Henning, A. E. Tuinenburg, M. Wietses, J. G. Grandjean, A. A. M. Wilde, W. H. Van Gilst, and H. J. G. M. Crijns Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels J. Am. Coll. Cardiol., March 1, 2001; 37(3): 926 - 932. [Abstract] [Full Text] [PDF]
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H. Sun, D. Chartier, N. Leblanc, and S. Nattel Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes Cardiovasc Res, March 1, 2001; 49(4): 751 - 761. [Abstract] [Full Text] [PDF]
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S. Fareh, A. Benardeau, and S. Nattel Differential efficacy of L- and T-type calcium channel blockers in preventing tachycardia-induced atrial remodeling in dogs Cardiovasc Res, March 1, 2001; 49(4): 762 - 770. [Abstract] [Full Text] [PDF]
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B. J. J. M. Brundel, I. C. Van Gelder, R. H. Henning, R. G. Tieleman, A. E. Tuinenburg, M. Wietses, J. G. Grandjean, W. H. Van Gilst, and H. J. G. M. Crijns Ion Channel Remodeling Is Related to Intraoperative Atrial Effective Refractory Periods in Patients With Paroxysmal and Persistent Atrial Fibrillation Circulation, February 6, 2001; 103(5): 684 - 690. [Abstract] [Full Text] [PDF]
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G. T. Altemose, D. P. Zipes, J. Weksler, J. M. Miller, and J. E. Olgin Inhibition of the Na+/H+ Exchanger Delays the Development of Rapid Pacing-Induced Atrial Contractile Dysfunction Circulation, February 6, 2001; 103(5): 762 - 768. [Abstract] [Full Text] [PDF]
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C. J. Meurling, J. E. P. Waktare, F. Holmqvist, A. Hedman, A. J. Camm, S. B. Olsson, and M. Malik Diurnal variations of the dominant cycle length of chronic atrial fibrillation Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H401 - H406. [Abstract] [Full Text] [PDF]
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C. Pandozi, L. Bianconi, L. Calo, A. Castro, F. Lamberti, M. C. Scianaro, G. Gentilucci, and M. Santini Postcardioversion atrial electrophysiologic changes induced by oral verapamil in patients with persistent atrial fibrillation J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2234 - 2241. [Abstract] [Full Text] [PDF]
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C. Sticherling, H. Oral, J. Horrocks, S. P. Chough, R. L. Baker, M. H. Kim, K. Wasmer, F. Pelosi, B. P. Knight, G. F. Michaud, et al. Effects of Digoxin on Acute, Atrial Fibrillation-Induced Changes in Atrial Refractoriness Circulation, November 14, 2000; 102(20): 2503 - 2508. [Abstract] [Full Text] [PDF]
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H. S. Friedman, M. Win, A. Hussain, and A. Sinha Effects of Cardiac Glycosides on Atrial Contractile Dysfunction After Short-term Atrial Fibrillation Chest, October 1, 2000; 118(4): 1116 - 1126. [Abstract] [Full Text] [PDF]
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R. J. Ramirez, S. Nattel, and M. Courtemanche Mathematical analysis of canine atrial action potentials: rate, regional factors, and electrical remodeling Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1767 - H1785. [Abstract] [Full Text] [PDF]
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T. H. Everett IV, H. Li, J. M. Mangrum, I. D. McRury, M. A. Mitchell, J. A. Redick, and D. E. Haines Electrical, Morphological, and Ultrastructural Remodeling and Reverse Remodeling in a Canine Model of Chronic Atrial Fibrillation Circulation, September 19, 2000; 102(12): 1454 - 1460. [Abstract] [Full Text] [PDF]
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S. Nattel and D. Li Ionic Remodeling in the Heart : Pathophysiological Significance and New Therapeutic Opportunities for Atrial Fibrillation Circ. Res., September 15, 2000; 87(6): 440 - 447. [Abstract] [Full Text] [PDF]
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H. J. Sih, D. P. Zipes, E. J. Berbari, D. E. Adams, and J. E. Olgin Differences in organization between acute and chronic atrial fibrillation in dogs J. Am. Coll. Cardiol., September 1, 2000; 36(3): 924 - 931. [Abstract] [Full Text] [PDF]
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 C.J. Garratt and S.P. Fynn Atrial electrical remodelling and atrial fibrillation QJM, September 1, 2000; 93(9): 563 - 565. [Full Text] [PDF]
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E. G. Manios, E. M. Kanoupakis, G. I. Chlouverakis, M. D. Kaleboubas, H. E. Mavrakis, and P. E. Vardas Changes in atrial electrical properties following cardioversion of chronic atrial fibrillation: relation with recurrence Cardiovasc Res, August 1, 2000; 47(2): 244 - 253. [Abstract] [Full Text] [PDF]
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D. Li, A. Benardeau, and S. Nattel Contrasting Efficacy of Dofetilide in Differing Experimental Models of Atrial Fibrillation Circulation, July 4, 2000; 102(1): 104 - 112. [Abstract] [Full Text] [PDF]
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