(Circulation. 1997;96:3157-3163.)
© 1997 American Heart Association, Inc.
Articles |
Structural Changes of Atrial Myocardium due to Sustained Atrial Fibrillation in the Goat
From the Department of Molecular Cell Biology and Genetics (J.A., M.B.) and Department of Physiology (M.W., M.A.), Cardiovascular Research Institute Maastricht, Maastricht University, Netherlands, and Janssen Research Foundation (F.T., L.W., M.B.), Beerse, Belgium.
Correspondence to Prof Dr M. Borgers, Department of Molecular Cell Biology and Genetics, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. E-mail secrmcb{at}molcelb.unimaas.nl
Background After cardioversion of sustained atrial fibrillation (AF), the electrical and contractile functions of the atria are impaired, and recurrences of AF frequently occur. Whether remodeling of the structure of atrial myocardium is the basis for this problem is not known.
Methods and Results Sustained AF was induced by electrical pacing in 13 goats instrumented long-term. The goats were killed after 9 to 23 weeks, and the atrial myocardium was examined by light and electron microscopy. The changes were quantified in left and right atrial free walls, appendages, trabeculae, the interatrial septum, and the bundle of Bachmann. A substantial proportion of the atrial myocytes (up to 92%) revealed marked changes in their cellular substructures, such as loss of myofibrils, accumulation of glycogen, changes in mitochondrial shape and size, fragmentation of sarcoplasmic reticulum, and dispersion of nuclear chromatin. These changes were accompanied by an increase in size of the myocytes (up to 195%). There were virtually no signs of cellular degeneration, and the interstitial space remained unaltered. The duration of sustained AF did not significantly affect the degree of myolytic cell changes.
Conclusions Sustained AF in goats leads to predominantly structural changes in the atrial myocytes similar to those seen in ventricular myocytes from chronic hibernating myocardium. These structural changes may explain the depressed contractile function of atrial myocardium after cardioversion. This goat model of AF offers a new approach to study the cascade of events leading to sustained AF and its maintenance.
Key Words: atrium • fibrillation • myocytes • structure • stunning, myocardial
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 F. Marin, V. Roldan, V. Climent, A. Garcia, P. Marco, and G. Y.H. Lip Is Thrombogenesis in Atrial Fibrillation Related to Matrix Metalloproteinase-1 and Its Inhibitor, TIMP-1? Stroke, May 1, 2003; 34(5): 1181 - 1186. [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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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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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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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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C. Dimmer, T. Szili-Torok, R. Tavernier, T. Verstraten, and L. J. Jordaens Initiating mechanisms of paroxysmal atrial fibrillation Europace, January 1, 2003; 5(1): 1 - 9. [Abstract] [PDF]
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S. A. Thomas, J. A. Fallavollita, G. Suzuki, M. Borgers, and J. M. Canty Jr Dissociation of Regional Adaptations to Ischemia and Global Myolysis in an Accelerated Swine Model of Chronic Hibernating Myocardium Circ. Res., November 15, 2002; 91(10): 970 - 977. [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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A. E. Schafler, K. Kirmanoglou, P. Pecher, A. Hannekum, and B. Schumacher Overexpression of heat shock protein 60/10 in myocardium of patients with chronic atrial fibrillation Ann. Thorac. Surg., September 1, 2002; 74(3): 767 - 770. [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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C. Rucker-Martin, F. Pecker, D. Godreau, and S. N Hatem Dedifferentiation of atrial myocytes during atrial fibrillation: role of fibroblast proliferation in vitro Cardiovasc Res, July 1, 2002; 55(1): 38 - 52. [Abstract] [Full Text] [PDF]
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 M. P. van den Berg, G. Tjeerdsma, P. J. de Kam, F. Boomsma, H. J.G.M. Crijns, and D. J. van Veldhuisen Longstanding atrial fibrillation causes depletion of atrial natriuretic peptide in patients with advanced congestive heart failure Eur J Heart Fail, June 1, 2002; 4(3): 255 - 262. [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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A. Goette, U. Lendeckel, and H. U Klein Signal transduction systems and atrial fibrillation Cardiovasc Res, May 1, 2002; 54(2): 247 - 258. [Abstract] [Full Text] [PDF]
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H. M.W van der Velden and H. J Jongsma Cardiac gap junctions and connexins: their role in atrial fibrillation and potential as therapeutic targets Cardiovasc Res, May 1, 2002; 54(2): 270 - 279. [Abstract] [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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S. Kostin, G. Klein, Z. Szalay, S. Hein, E. P Bauer, and J. Schaper Structural correlate of atrial fibrillation in human patients Cardiovasc Res, May 1, 2002; 54(2): 361 - 379. [Abstract] [Full Text] [PDF]
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B. J.J.M Brundel, J. Ausma, I. C van Gelder, J. J.L Van Der Want, W. H van Gilst, H. J.G.M Crijns, and R. H Henning Activation of proteolysis by calpains and structural changes in human paroxysmal and persistent atrial fibrillation Cardiovasc Res, May 1, 2002; 54(2): 380 - 389. [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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V. L.J.L Thijssen, H. M.W van der Velden, E. P van Ankeren, J. Ausma, M. A Allessie, M. Borgers, G. J.J.M van Eys, and H. J Jongsma Analysis of altered gene expression during sustained atrial fibrillation in the goat Cardiovasc Res, May 1, 2002; 54(2): 427 - 437. [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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