(Circulation. 1995;91:1588-1595.)
© 1995 American Heart Association, Inc.
Articles |
Chronic Rapid Atrial Pacing
Structural, Functional, and Electrophysiological Characteristics of a New Model of Sustained Atrial Fibrillation
From the Departments of Medicine (C.A.M., G.J.K., D.L.J.), Physiology (D.L.J.), and Pathology (C.M.G.), University of Western Ontario, and the Heart and Circulation Group, The John P. Robarts Research Institute (C.A.M., G.J.K., D.L.J), London, Ontario, Canada.
Correspondence to Carlos A. Morillo, MD, Cardiovascular Physiology, Rm 3C-124, McGuire VA Medical Center, 1201 Broad Rock Blvd, Richmond, VA 23249.
Background Despite the clinical importance of atrial fibrillation (AF), the development of chronic nonvalvular AF models has been difficult. Animal models of sustained AF have been developed primarily in the short-term setting. Recently, models of chronic ventricular myopathy and fibrillation have been developed after several weeks of continuous rapid ventricular pacing. We hypothesized that chronic rapid atrial pacing would lead to atrial myopathy, yielding a reproducible model of sustained AF.
Methods and Results Twenty-two halothane-anesthetized
mongrel dogs underwent insertion of a transvenous lead at the right
atrial appendage that was continuously paced at 400 beats per minute
for 6 weeks. Two-dimensional echocardiography was performed in 11 dogs
to assess the effects of rapid atrial pacing on atrial size. Atrial
vulnerability was defined as the ability to induce sustained repetitive
atrial responses during programmed electrical stimulation and was
assessed by extrastimulus and burst-pacing techniques. Effective
refractory period (ERP) was measured at two endocardial sites in the
right atrium. Sustained AF was defined as AF 
15 minutes. In animals
with sustained AF, 10 quadripolar epicardial electrodes were surgically
attached to the right and left atria. The local atrial fibrillatory
cycle length (AFCL) was measured in a 20-second window, and the mean
AFCL was measured at each site. Marked biatrial enlargement was
documented; after 6 weeks of continuous rapid atrial pacing, the left
atrium was 7.8±1 cm2 at baseline versus 11.3±1
cm2 after pacing, and the right atrium was 4.3±0.7
cm2 at baseline versus 7.2±1.3 cm2 after
pacing. An increase in atrial area of at least 40% was necessary to
induce sustained AF and was strongly correlated with the inducibility
of AF (r=.87). Electron microscopy of atrial tissue
demonstrated structural changes that were characterized by an increase
in mitochondrial size and number and by disruption of the sarcoplasmic
reticulum. After 6 weeks of continuous rapid atrial pacing, sustained
AF was induced in 18 dogs (82%) and nonsustained AF was induced in 2
dogs (9%). AF occurred spontaneously in 4 dogs (18%). Right atrial
ERP, measured at cycle lengths of 400 and 300 milliseconds at baseline,
was significantly shortened after pacing, from 150±8 to 127±10
milliseconds and from 147±11 to 123±12 milliseconds,
respectively (P<.001). This finding was highly predictive
of inducibility of AF (90%). Increased atrial area (40%) and ERP
shortening were highly predictive for the induction of sustained AF
(88%). Local epicardial ERP correlated well with local AFCL
(R2=.93). Mean AFCL was significantly shorter in
the left atrium (81±8 milliseconds) compared with the right atrium
94±9 milliseconds (P<.05). An area in the posterior left
atrium was consistently found to have a shorter AFCL (74±5
milliseconds). Cryoablation of this area was attempted in 11 dogs. In 9
dogs (82%; mean, 9.0±4.0; range, 5 to 14), AF was terminated and no
longer induced after serial cryoablation.
Conclusions Sustained AF was readily inducible in most dogs (82%) after rapid atrial pacing. This model was consistently associated with biatrial myopathy and marked changes in atrial vulnerability. An area in the posterior left atrium was uniformly shown to have the shortest AFCL. The results of restoration of sinus rhythm and prevention of inducibility of AF after cryoablation of this area of the left atrium suggest that this area may be critical in the maintenance of AF in this model.
Key Words: fibrillation • electrophysiology
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H. J.J. Wellens Cardiac arrhythmias: The quest for a cure: A historical perspective J. Am. Coll. Cardiol., September 15, 2004; 44(6): 1155 - 1163. [Abstract] [Full Text] [PDF]
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T. Taneja, G. Horvath, D. K. Racker, D. Johnson, J. Goldberger, and A. Kadish Is there a correlation between ventricular fibrillation cycle length and electrophysiological and anatomic properties of the canine left ventricle? Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H823 - H832. [Abstract] [Full Text] [PDF]
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S. Verheule, E. Wilson, S. Banthia, T. H. Everett IV, S. Shanbhag, H. J. Sih, and J. Olgin Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H634 - H644. [Abstract] [Full Text] [PDF]
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M. Haissaguerre, P. Sanders, M. Hocini, L.-F. Hsu, D. C. Shah, C. Scavee, Y. Takahashi, M. Rotter, J.-L. Pasquie, S. Garrigue, et al. Changes in Atrial Fibrillation Cycle Length and Inducibility During Catheter Ablation and Their Relation to Outcome Circulation, June 22, 2004; 109(24): 3007 - 3013. [Abstract] [Full Text] [PDF]
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G. G. de Lima, R. A. K. Kalil, T. L. L. Leiria, D. M. Hatem, C. L. Kruse, R. Abrahao, J. R. M. Sant'anna, P. R. Prates, and I. A. Nesralla Randomized study of surgery for patients with permanent atrial fibrillation as a result of mitral valve disease Ann. Thorac. Surg., June 1, 2004; 77(6): 2089 - 2094. [Abstract] [Full Text] [PDF]
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A. M. Park, C.-C. Chou, P. C. Drury, Y. Okuyama, A. Peter, A. Hamabe, Y. Miyauchi, R. M. Kass, H. S. Karagueuzian, M. C. Fishbein, et al. Thoracic vein ablation terminates chronic atrial fibrillation in dogs Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2072 - H2077. [Abstract] [Full Text] [PDF]
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T. H. Everett IV, S. Verheule, E. E. Wilson, S. Foreman, and J. E. Olgin Left atrial dilatation resulting from chronic mitral regurgitation decreases spatiotemporal organization of atrial fibrillation in left atrium Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2452 - H2460. [Abstract] [Full Text] [PDF]
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D. M. Todd, S. P. Fynn, A. P. Walden, W. J. Hobbs, S. Arya, and C. J. Garratt Repetitive 4-Week Periods of Atrial Electrical Remodeling Promote Stability of Atrial Fibrillation: Time Course of a Second Factor Involved in the Self-Perpetuation of Atrial Fibrillation Circulation, March 23, 2004; 109(11): 1434 - 1439. [Abstract] [Full Text] [PDF]
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Y. Nakano, S. Niida, K. Dote, S. Takenaka, H. Hirao, F. Miura, M. Ishida, T. Shingu, T. Sueda, M. Yoshizumi, et al. Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation J. Am. Coll. Cardiol., March 3, 2004; 43(5): 818 - 825. [Abstract] [Full Text] [PDF]
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P. Spurrell, K. Kamalvand, M. Higson, and N. Sulke Temporal changes in atrial refractoriness following DC cardioversion of persistent atrial fibrillation in man Europace, January 1, 2004; 6(3): 229 - 235. [Abstract] [Full Text] [PDF]
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D. M. Todd, A. C. Skanes, G. Guiraudon, C. Guiraudon, A. D. Krahn, R. Yee, and G. J. Klein Role of the Posterior Left Atrium and Pulmonary Veins in Human Lone Atrial Fibrillation: Electrophysiological and Pathological Data From Patients Undergoing Atrial Fibrillation Surgery Circulation, December 23, 2003; 108(25): 3108 - 3114. [Abstract] [Full Text] [PDF]
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P. Chandra, T. S Rosen, B. Herweg, P. Danilo Jr., and M. R Rosen Left atrial pacing induces memory and is associated with atrial tachyarrhythmias Cardiovasc Res, November 1, 2003; 60(2): 307 - 314. [Abstract] [Full Text] [PDF]
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H.-M. Lo, F.-Y. Lin, and Y. Z. Tseng Atrial compartment operation for atrial fibrillation: to isolate the left atrium or not? Ann. Thorac. Surg., October 1, 2003; 76(4): 1259 - 1263. [Abstract] [Full Text] [PDF]
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W. Dun, P. Chandra, P. Danilo Jr., M. R. Rosen, and P. A. Boyden Chronic atrial fibrillation does not further decrease outward currents. It increases them. Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1378 - H1384. [Abstract] [Full Text] [PDF]
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M. C. Sanguinetti and P. B. Bennett Antiarrhythmic Drug Target Choices and Screening Circ. Res., September 19, 2003; 93(6): 491 - 499. [Abstract] [Full Text] [PDF]
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 J. R Ehrlich, T.-J. Cha, L. Zhang, D. Chartier, P. Melnyk, S. H Hohnloser, and S. Nattel Cellular electrophysiology of canine pulmonary vein cardiomyocytes: action potential and ionic current properties J. Physiol., September 15, 2003; 551(3): 801 - 813. [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. Ausma, H. M.W. van der Velden, M.-H. Lenders, E. P. van Ankeren, H. J. Jongsma, F. C.S. Ramaekers, M. Borgers, and M. A. Allessie Reverse Structural and Gap-Junctional Remodeling After Prolonged Atrial Fibrillation in the Goat Circulation, April 22, 2003; 107(15): 2051 - 2058. [Abstract] [Full Text] [PDF]
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L.-P. Lai, C.-C. Tsai, M.-J. Su, J.-L. Lin, Y.-S. Chen, Y.-Z. Tseng, and S. K. S. Huang Atrial Fibrillation Is Associated With Accumulation of Aging-Related Common Type Mitochondrial DNA Deletion Mutation in Human Atrial Tissue Chest, February 1, 2003; 123(2): 539 - 544. [Abstract] [Full Text] [PDF]
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 N. Colangelo, S. Benussi, S. Nascimbene, S. Calvi, A. Caldarola, G. Piazza, A. Castiglioni, J. Q. Melo, and O. Alfieri Cardiopulmonary bypass strategy during concomitant surgical treatment of mitral valve disease and atrial fibrillation Perfusion, January 1, 2003; 18(1): 19 - 24. [Abstract] [PDF]
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N. Sulke, P. Spurrell, K. Kamalvand, A. Mitchell, M. Higson, J. Gill, and V. Paul The effect of endocardial defibrillator shocks on basic atrial electrophysiology in man: Is post cardioversion atrial electrical 'remodelling' artefact? Europace, January 1, 2003; 5(1): 33 - 37. [Abstract] [PDF]
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R. Mantovan, M. A. Gatzoulis, A. Pedrocco, P. Ius, C. Cavallini, A. De Leo, R. Zecchel, V. Calzolari, C. Valfre, and P. Stritoni Supraventricular arrhythmia before and after surgical closure of atrial septal defects: spectrum, prognosis and management Europace, January 1, 2003; 5(2): 133 - 138. [Abstract] [PDF]
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T. H. Everett IV, J. G. Akar, L.-C. Kok, J. R. Moorman, and D. E. Haines Use of global atrial fibrillation organization to optimize the success of burst pace termination J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1831 - 1840. [Abstract] [Full Text] [PDF]
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E. Bertaglia, D. D'Este, F. Zerbo, F. Zoppo, P. Delise, and P. Pascotto Success of serial external electrical cardioversion of persistent atrial fibrillation in maintaining sinus rhythm. A randomized study Eur. Heart J., October 1, 2002; 23(19): 1522 - 1528. [Abstract] [Full Text] [PDF]
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S. Zhou, C.-M. Chang, T.-J. Wu, Y. Miyauchi, Y. Okuyama, A. M. Park, A. Hamabe, C. Omichi, H. Hayashi, L. A. Brodsky, et al. Nonreentrant focal activations in pulmonary veins in canine model of sustained atrial fibrillation Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1244 - H1252. [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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O. Berenfeld, A. V. Zaitsev, S. F. Mironov, A. M. Pertsov, and J. Jalife Frequency-Dependent Breakdown of Wave Propagation Into Fibrillatory Conduction Across the Pectinate Muscle Network in the Isolated Sheep Right Atrium Circ. Res., June 14, 2002; 90(11): 1173 - 1180. [Abstract] [Full Text] [PDF]
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K. Fan, K. L. Lee, W.-H. Chow, E. Chau, and C.-P. Lau Internal Cardioversion of Chronic Atrial Fibrillation During Percutaneous Mitral Commissurotomy: Insight Into Reversal of Chronic Stretch-Induced Atrial Remodeling Circulation, June 11, 2002; 105(23): 2746 - 2752. [Abstract] [Full Text] [PDF]
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K. Oahara, Y. Miyauchi, T. Ohara, M. C. Fishbein, S. Zhou, M.-H. Lee, W. J. Mandel, P.-S. Chen, and H. S. Karagueuzian Downregulation of Immunodetectable Atrial Connexin4O in a Canine Model of Chronic Left Ventricular Myocardial Infarction: Implications to Atrial Fibrillation Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2002; 7(2): 89 - 94. [Abstract] [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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