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(Circulation. 1997;95:988-996.)
© 1997 American Heart Association, Inc.
Articles |
Disturbed Connexin43 Gap Junction Distribution Correlates With the Location of Reentrant Circuits in the Epicardial Border Zone of Healing Canine Infarcts That Cause Ventricular Tachycardia
the Department of Cardiology, St Mary's Hospital (N.S.P.) and Imperial College School of Medicine (N.S.P., N.J.S.), London, UK; and Departments of Pharmacology (N.S.P., A.L.W.) and Medicine (J.C.), College of Physicians and Surgeons, Columbia University, New York, NY.
Correspondence to Dr Nicholas S. Peters, Academic Cardiology, St Mary's Hospital, Praed St, London W2 1NY, UK. E-mail n.peters@ic.ac.uk.
Background Slow, nonuniform conduction caused by abnormal gap-junctional coupling of infarct-related myocardium is thought to be a component of the arrhythmogenic substrate. The hypothesis that changes in gap-junctional distribution in the epicardial border zone (EBZ) of healing canine infarcts define the locations of reentrant ventricular tachycardia (VT) circuits was tested by correlating activation maps of the surviving subepicardial myocardial layer with immunolocalization of the principal gap-junctional protein, connexin43 (Cx43).
Methods and Results The EBZ overlying 4-day-old anterior infarcts in three dogs with inducible VT and three noninducible dogs was mapped with a high-resolution electrode array and systematically examined by standard histology and confocal immunolocalization of Cx43. The thickness of the EBZ was significantly less in the hearts with (538±257 µm) than without (840±132 µm; P<.05) VT. At the interface with the underlying necrotic cells, the EBZ myocardium showed a marked disruption of gap-junctional distribution, with Cx43 labeling abnormally arrayed longitudinally along the lateral surfaces of the cells. In the EBZ of all hearts, the disrupted Cx43 labeling extended part of the way to the epicardial surface, with the most superficial epicardial myocytes having the normal transversely orientated pattern. Only in the hearts with inducible VT did the disorganization extend through the full thickness of the surviving layer at sites correlating with the location of the central common pathways of the figure-of-8 reentrant VT circuits.
Conclusions Altered gap-junctional distribution is part of the early remodeling of myocardium after infarction, and by defining the location of the common central pathway of the reentrant VT circuits, it may be a determinant of VT susceptibility.
Key Words: connexin • immunohistochemistry • anisotropy • conduction • mapping
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F. G. Akar, B. J. Roth, and D. S. Rosenbaum Optical measurement of cell-to-cell coupling in intact heart using subthreshold electrical stimulation Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H533 - H542. [Abstract] [Full Text] [PDF]
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T. A.B. van Veen, H. V.M. van Rijen, and T. Opthof Cardiac gap junction channels: modulation of expression and channel properties Cardiovasc Res, August 1, 2001; 51(2): 217 - 229. [Abstract] [Full Text] [PDF]
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E. J. Ciaccio, A. C. Tosti, and M. M. Scheinman Relationship Between Sinus Rhythm Activation and the Reentrant Ventricular Tachycardia Isthmus Circulation, July 31, 2001; 104(5): 613 - 619. [Abstract] [Full Text] [PDF]
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M. Ruiz-Meana, D. Garcia-Dorado, S. Lane, P. Pina, J. Inserte, M. Mirabet, and J. Soler-Soler Persistence of gap junction communication during myocardial ischemia Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2563 - H2571. [Abstract] [Full Text] [PDF]
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J. R de Groot, F. J.G Wilms-Schopman, T. Opthof, C. A Remme, and R. Coronel Late ventricular arrhythmias during acute regional ischemia in the isolated blood perfused pig heart Role of electrical cellular coupling Cardiovasc Res, May 1, 2001; 50(2): 362 - 372. [Abstract] [Full Text] [PDF]
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M. S. Spach Mechanisms of the Dynamics of Reentry in a Fibrillating Myocardium : Developing a Genes-to-Rotors Paradigm Circ. Res., April 27, 2001; 88(8): 753 - 755. [Full Text] [PDF]
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 J. M. Burt, A. M. Fletcher, T. D. Steele, Y. Wu, G. T. Cottrell, and D. T. Kurjiaka Alteration of Cx43:Cx40 expression ratio in A7r5 cells Am J Physiol Cell Physiol, March 1, 2001; 280(3): C500 - C508. [Abstract] [Full Text] [PDF]
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D. J. Huelsing, A. E. Pollard, and K. W. Spitzer Transient outward current modulates discontinuous conduction in rabbit ventricular cell pairs Cardiovasc Res, March 1, 2001; 49(4): 779 - 789. [Abstract] [Full Text] [PDF]
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M. S. Hanna, J. Coromilas, M. E. Josephson, A. L. Wit, and N. S. Peters Mechanisms of Resetting Reentrant Circuits in Canine Ventricular Tachycardia Circulation, February 27, 2001; 103(8): 1148 - 1156. [Abstract] [Full Text] [PDF]
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D. E. Gutstein, G. E. Morley, H. Tamaddon, D. Vaidya, M. D. Schneider, J. Chen, K. R. Chien, H. Stuhlmann, and G. I. Fishman Conduction Slowing and Sudden Arrhythmic Death in Mice With Cardiac-Restricted Inactivation of Connexin43 Circ. Res., February 16, 2001; 88(3): 333 - 339. [Abstract] [Full Text] [PDF]
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J. M. Pastore and D. S. Rosenbaum Role of Structural Barriers in the Mechanism of Alternans-Induced Reentry Circ. Res., December 8, 2000; 87(12): 1157 - 1163. [Abstract] [Full Text] [PDF]
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M. J. Schalij, L. Boersma, M. Huijberts, and M. A. Allessie Anisotropic Reentry in a Perfused 2-Dimensional Layer of Rabbit Ventricular Myocardium Circulation, November 21, 2000; 102(21): 2650 - 2658. [Abstract] [Full Text] [PDF]
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C. Cabo, H. Schmitt, and A. L. Wit New Mechanism of Antiarrhythmic Drug Action : Increasing L-Type Calcium Current Prevents Reentrant Ventricular Tachycardia in the Infarcted Canine Heart Circulation, November 7, 2000; 102(19): 2417 - 2425. [Abstract] [Full Text] [PDF]
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M. A. Beardslee, D. L. Lerner, P. N. Tadros, J. G. Laing, E. C. Beyer, K. A. Yamada, A. G. Kleber, R. B. Schuessler, and J. E. Saffitz Dephosphorylation and Intracellular Redistribution of Ventricular Connexin43 During Electrical Uncoupling Induced by Ischemia Circ. Res., October 13, 2000; 87(8): 656 - 662. [Abstract] [Full Text] [PDF]
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G. Taimor Cardiac gap junctions: good or bad? Cardiovasc Res, October 1, 2000; 48(1): 8 - 10. [Full Text] [PDF]
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S. P. Thomas, L. Bircher-Lehmann, S. A. Thomas, J. Zhuang, J. E. Saffitz, and A. G. Kleber Synthetic Strands of Neonatal Mouse Cardiac Myocytes : Structural and Electrophysiological Properties Circ. Res., September 15, 2000; 87(6): 467 - 473. [Abstract] [Full Text] [PDF]
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H. J. Jongsma and R. Wilders Gap Junctions in Cardiovascular Disease Circ. Res., June 23, 2000; 86(12): 1193 - 1197. [Abstract] [Full Text] [PDF]
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D. S. He and J. M. Burt Mechanism and Selectivity of the Effects of Halothane on Gap Junction Channel Function Circ. Res., June 9, 2000; 86 (11): e104 - e109. [Abstract] [Full Text] [PDF]
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M. Yashima, T. Ohara, J.-M. Cao, Y.-H. Kim, M. C. Fishbein, W. J. Mandel, P.-S. Chen, and H. S. Karagueuzian Nicotine increases ventricular vulnerability to fibrillation in hearts with healed myocardial infarction Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H2124 - H2133. [Abstract] [Full Text] [PDF]
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H. M.W. van der Velden, J. Ausma, M. B. Rook, A. J.C.G.M. Hellemons, T. A.A.B. van Veen, M. A. Allessie, and H. J. Jongsma Gap junctional remodeling in relation to stabilization of atrial fibrillation in the goat Cardiovasc Res, June 1, 2000; 46(3): 476 - 486. [Abstract] [Full Text] [PDF]
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J. E. Saffitz, K. G. Green, W. J. Kraft, K. B. Schechtman, and K. A. Yamada Effects of diminished expression of connexin43 on gap junction number and size in ventricular myocardium Am J Physiol Heart Circ Physiol, May 1, 2000; 278(5): H1662 - H1670. [Abstract] [Full Text] [PDF]
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