© 1997 American Heart Association, Inc.
Articles |
Ionic Remodeling Underlying Action Potential Changes in a Canine Model of Atrial Fibrillation
From the Department of Medicine, Montreal Heart Institute (J.F., R.G., G.-R.L., Z.W., S.N.) and University of Montreal (R.G., G.-R.L., Z.W., S.N.), and the Department of Pharmacology and Therapeutics, McGill University (L.Y., S.N.), Montreal, Quebec, Canada.
Correspondence to Stanley Nattel, MD, Research Center, Montreal Heart Institute, 5000 Bélanger St, Montreal, Quebec H1T 1C8, Canada.
Abstract Rapid electrical activation, as occurs during atrial fibrillation (AF), is known to cause reductions in atrial refractoriness and in adaptation to heart rate of the atrial refractory period, which promote the maintenance of AF, but the underlying ionic mechanisms are unknown. In order to determine the cellular and ionic changes caused by chronic atrial tachycardia, we studied right atrial myocytes from dogs subjected to 1, 7, or 42 days of atrial pacing at 400/min and compared them with myocytes from sham-operated dogs (pacemaker inserted but not activated). Rapid pacing led to progressive increases in the duration of AF induced by bursts of 10-Hz stimuli (from 3±2 seconds in sham-operated dogs to 3060±707 seconds in dogs after 42 days of pacing, P<.001) and reduced atrial refractoriness and adaptation to rate of the atrial refractory period. Voltage-clamp studies showed that chronic rapid pacing did not alter inward rectifier K+ current, rapid or slow components of the delayed rectifier current, the ultrarapid delayed rectifier current, T-type Ca2+ current, or Ca2+-dependent Cl- current. In contrast, the densities of transient outward current (Ito) and L-type Ca2+ current (ICa) were progressively reduced as the duration of rapid pacing increased, without concomitant changes in kinetics or voltage dependence. In keeping with in vivo changes in refractoriness, action potential duration (APD) and APD adaptation to rate were decreased by rapid pacing. The response of the action potential and ionic currents flowing during the action potential (as exposed by action-potential voltage clamp) to nifedipine in normal canine cells and in cells from rapidly paced dogs suggested that the APD changes in paced dogs were largely due to reductions in ICa. We conclude that sustained atrial tachycardia reduces Ito and ICa, that the reduced ICa decreases APD and APD adaptation to rate, and that these cellular changes likely account for the alterations in atrial refractoriness associated with enhanced ability to maintain AF in the model.
Key Words: Ca2+ channel • K+ channel • cardiac arrhythmia • cardiac ionic current • action potential
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A. J Workman, K. A Kane, and A. C Rankin Characterisation of the Na, K pump current in atrial cells from patients with and without chronic atrial fibrillation Cardiovasc Res, September 1, 2003; 59(3): 593 - 602. [Abstract] [Full Text] [PDF]
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Y. Miyauchi, S. Zhou, Y. Okuyama, M. Miyauchi, H. Hayashi, A. Hamabe, M. C. Fishbein, W. J. Mandel, L. S. Chen, P.-S. Chen, et al. Altered Atrial Electrical Restitution and Heterogeneous Sympathetic Hyperinnervation in Hearts With Chronic Left Ventricular Myocardial Infarction: Implications for Atrial Fibrillation Circulation, July 22, 2003; 108(3): 360 - 366. [Abstract] [Full Text] [PDF]
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G. Klein, F. Schroder, D. Vogler, A. Schaefer, A. Haverich, B. Schieffer, T. Korte, and H. Drexler Increased open probability of single cardiac L-type calcium channels in patients with chronic atrial fibrillation: Role of phosphatase 2A Cardiovasc Res, July 1, 2003; 59(1): 37 - 45. [Abstract] [Full Text] [PDF]
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C. Valenzuela Pharmacological electrical remodelling in human atria induced by chronic {beta}-blockade Cardiovasc Res, June 1, 2003; 58(3): 498 - 500. [Full Text] [PDF]
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W. Dun, T. Yagi, M. R Rosen, and P. A Boyden Calcium and potassium currents in cells from adult and aged canine right atria Cardiovasc Res, June 1, 2003; 58(3): 526 - 534. [Abstract] [Full Text] [PDF]
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S. Verheule, E. Wilson, T. Everett IV, S. Shanbhag, C. Golden, and J. Olgin Alterations in Atrial Electrophysiology and Tissue Structure in a Canine Model of Chronic Atrial Dilatation Due to Mitral Regurgitation Circulation, May 27, 2003; 107(20): 2615 - 2622. [Abstract] [Full Text] [PDF]
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J. G. Akar, T. H. Everett, R. Ho, J. Craft, D. E. Haines, A. P. Somlyo, and A. V. Somlyo Intracellular Chloride Accumulation and Subcellular Elemental Distribution During Atrial Fibrillation Circulation, April 8, 2003; 107(13): 1810 - 1815. [Abstract] [Full Text] [PDF]
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U. Schotten, M. Duytschaever, J. Ausma, S. Eijsbouts, H.-R. Neuberger, and M. Allessie Electrical and Contractile Remodeling During the First Days of Atrial Fibrillation Go Hand in Hand Circulation, March 18, 2003; 107(10): 1433 - 1439. [Abstract] [Full Text] [PDF]
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K. Shinagawa, A. Shiroshita-Takeshita, G. Schram, and S. Nattel Effects of Antiarrhythmic Drugs on Fibrillation in the Remodeled Atrium: Insights Into the Mechanism of the Superior Efficacy of Amiodarone Circulation, March 18, 2003; 107(10): 1440 - 1446. [Abstract] [Full Text] [PDF]
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R. F. Bosch, C. R. Scherer, N. Rub, S. Wohrl, K. Steinmeyer, H. Haase, A. E. Busch, L. Seipel, and V. Kuhlkamp Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces ICa,L and Ito in rapid atrial pacing in rabbits J. Am. Coll. Cardiol., March 5, 2003; 41(5): 858 - 869. [Abstract] [Full Text] [PDF]
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 S. Nattel Atrial Electrophysiology and Mechanisms of Atrial Fibrillation Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2003; 8(1_suppl): S5 - S11. [Abstract] [PDF]
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 P. Khairy and S. Nattel New insights into the mechanisms and management of atrial fibrillation Can. Med. Assoc. J., October 29, 2002; 167(9): 1012 - 1020. [Abstract] [Full Text] [PDF]
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S. M. Narayan, F. Bode, P. L. Karasik, and M. R. Franz Alternans of Atrial Action Potentials During Atrial Flutter as a Precursor to Atrial Fibrillation Circulation, October 8, 2002; 106(15): 1968 - 1973. [Abstract] [Full Text] [PDF]
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P. Sanders, J. B. Morton, J. G. Morgan, N. C. Davidson, S. J. Spence, J. K. Vohra, J. M. Kalman, and P. B. Sparks Reversal of Atrial Mechanical Stunning After Cardioversion of Atrial Arrhythmias: Implications for the Mechanisms of Tachycardia-Mediated Atrial Cardiomyopathy Circulation, October 1, 2002; 106(14): 1806 - 1813. [Abstract] [Full Text] [PDF]
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T. Ohara, Z. Qu, M.-H. Lee, K. Ohara, C. Omichi, W. J. Mandel, P.-S. Chen, and H. S. Karagueuzian Increased vulnerability to inducible atrial fibrillation caused by partial cellular uncoupling with heptanol Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1116 - H1122. [Abstract] [Full Text] [PDF]
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S. Verheule, E. E Wilson, R. Arora, S. K Engle, L. R Scott, and J. E Olgin Tissue structure and connexin expression of canine pulmonary veins Cardiovasc Res, September 1, 2002; 55(4): 727 - 738. [Abstract] [Full Text] [PDF]
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A. Goette, M. Arndt, C. Rocken, T. Staack, R. Bechtloff, D. Reinhold, C. Huth, S. Ansorge, H. U. Klein, and U. Lendeckel Calpains and cytokines in fibrillating human atria Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H264 - H272. [Abstract] [Full Text] [PDF]
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J. Ausma and M. Borgers Dedifferentiation of atrial cardiomyocytes: from in vivo to in vitro Cardiovasc Res, July 1, 2002; 55(1): 9 - 12. [Full Text] [PDF]
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G. Schram, M. Pourrier, P. Melnyk, and S. Nattel Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function Circ. Res., May 17, 2002; 90(9): 939 - 950. [Abstract] [Full Text] [PDF]
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J. Kneller, R. Zou, E. J. Vigmond, Z. Wang, L. J. Leon, and S. Nattel Cholinergic Atrial Fibrillation in a Computer Model of a Two-Dimensional Sheet of Canine Atrial Cells With Realistic Ionic Properties Circ. Res., May 17, 2002; 90 (9): e73 - e87. [Abstract] [Full Text] [PDF]
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J. Jalife, O. Berenfeld, and M. Mansour Mother rotors and fibrillatory conduction: a mechanism of atrial fibrillation Cardiovasc Res, May 1, 2002; 54(2): 204 - 216. [Abstract] [Full Text] [PDF]
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M. Allessie, J. Ausma, and U. Schotten Electrical, contractile and structural remodeling during atrial fibrillation Cardiovasc Res, May 1, 2002; 54(2): 230 - 246. [Abstract] [Full Text] [PDF]
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R. F Bosch and S. Nattel Cellular electrophysiology of atrial fibrillation Cardiovasc Res, May 1, 2002; 54(2): 259 - 269. [Full Text] [PDF]
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B. J.J.M. Brundel, R. H. Henning, H. H. Kampinga, I. C. Van Gelder, and H. J.G.M. Crijns Molecular mechanisms of remodeling in human atrial fibrillation Cardiovasc Res, May 1, 2002; 54(2): 315 - 324. [Abstract] [Full Text] [PDF]
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S. Nattel Therapeutic implications of atrial fibrillation mechanisms: can mechanistic insights be used to improve AF management? Cardiovasc Res, May 1, 2002; 54(2): 347 - 360. [Abstract] [Full Text] [PDF]
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T. Yagi, J. Pu, P. Chandra, M. Hara, P. Danilo Jr., M. R Rosen, and P. A Boyden Density and function of inward currents in right atrial cells from chronically fibrillating canine atria Cardiovasc Res, May 1, 2002; 54(2): 405 - 415. [Abstract] [Full Text] [PDF]
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J. Kneller, H. Sun, N. Leblanc, and S. Nattel Remodeling of Ca2+-handling by atrial tachycardia: evidence for a role in loss of rate-adaptation Cardiovasc Res, May 1, 2002; 54(2): 416 - 426. [Abstract] [Full Text] [PDF]
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K. Shinagawa, H. Mitamura, S. Ogawa, and S. Nattel Effects of inhibiting Na+/H+-exchange or angiotensin converting enzyme on atrial tachycardia-induced remodeling Cardiovasc Res, May 1, 2002; 54(2): 438 - 446. [Abstract] [Full Text] [PDF]
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