(Circulation. 1997;95:1945-1953.)
© 1997 American Heart Association, Inc.
Articles |
Verapamil Reduces Tachycardia-Induced Electrical Remodeling of the Atria
Presented in part at the 68th Scientific Sessions of the American Heart Association, Anaheim, Calif, November 13-16, 1995, and published in abstract form (Circulation. 1995;92[suppl I]:I-754.).
From the Department of Cardiology, Thoraxcenter, University Hospital Groningen; the Department of Clinical Pharmacology, University of Groningen; and the Department of Physiology, University of Limburg, Netherlands.
Correspondence to R.G. Tieleman, MD, Department of Cardiology, Thoraxcenter, University Hospital Groningen, PO Box 30001, 9700 RB Groningen, Netherlands.
Background Prolonged periods of atrial fibrillation or rapid atrial pacing induce shortening of the atrial effective refractory period (AERP), which is thought to be related to the lower success rates of various antifibrillatory treatments when the arrhythmia has lasted for a longer period of time.
Methods and Results To investigate whether an increase in intracellular calcium could be the stimulus for electrical remodeling, the effects of verapamil on shortening of the AERP in response to 24 hours of rapid atrial pacing (300 bpm) were studied in five chronically instrumented conscious goats during infusion of saline or verapamil. During rapid atrial pacing, the ventricular rate was kept constant by ventricular pacing (150 bpm). The AERP was measured by programmed electrical stimulation at basic cycle lengths of 430, 300, and 200 ms. Verapamil had no effects on the AERP before rapid atrial pacing. However, in the course of 24 hours of rapid atrial pacing, the AERP shortened significantly less (27% to 58%) in the presence of verapamil compared with control (at 430, 300, and 200 ms, P<.001, P<.01, and P<.01, respectively). Also, after cessation of pacing, complete recovery of the AERP during verapamil infusion occurred much sooner than in the control experiments. Despite a significant reduction in electrical remodeling, there was only a minimal reduction in inducibility of atrial fibrillation by verapamil (34% versus 39% in the control experiments, P=.03).
Conclusions Electrical remodeling of the atrium during rapid atrial pacing was significantly attenuated by verapamil. This suggests that electrical remodeling of the atrium is triggered by the high calcium influx during rapid atrial pacing rates.
Key Words: fibrillation • atrium • remodeling • calcium • electrophysiology
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S. Zhang, Z. Zhou, Q. Gong, J. C. Makielski, and C. T. January Mechanism of Block and Identification of the Verapamil Binding Domain to HERG Potassium Channels Circ. Res., May 14, 1999; 84(9): 989 - 998. [Abstract] [Full Text] [PDF]
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S. Nattel Atrial electrophysiological remodeling caused by rapid atrial activation: underlying mechanisms and clinical relevance to atrial fibrillation Cardiovasc Res, May 1, 1999; 42(2): 298 - 308. [Abstract] [Full Text] [PDF]
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M. Hara, A. Shvilkin, M. R Rosen, P. Danilo Jr., and P. A Boyden Steady-state and nonsteady-state action potentials in fibrillating canine atrium: abnormal rate adaptation and its possible mechanisms Cardiovasc Res, May 1, 1999; 42(2): 455 - 469. [Abstract] [Full Text] [PDF]
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W.-C. Yu, S.-H. Lee, C.-T. Tai, C.-F. Tsai, M.-H. Hsieh, C.-C. Chen, Y.-A. Ding, M.-S. Chang, and S.-A. Chen Reversal of atrial electrical remodeling following cardioversion of long-standing atrial fibrillation in man Cardiovasc Res, May 1, 1999; 42(2): 470 - 476. [Abstract] [Full Text] [PDF]
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M. Courtemanche, R. J Ramirez, and S. Nattel Ionic targets for drug therapy and atrial fibrillation-induced electrical remodeling: insights from a mathematical model Cardiovasc Res, May 1, 1999; 42(2): 477 - 489. [Abstract] [Full Text] [PDF]
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L. Yue, P. Melnyk, R. Gaspo, Z. Wang, and S. Nattel Molecular Mechanisms Underlying Ionic Remodeling in a Dog Model of Atrial Fibrillation Circ. Res., April 16, 1999; 84(7): 776 - 784. [Abstract] [Full Text] [PDF]
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L.-P. Lai, M.-J. Su, J.-L. Lin, F.-Y. Lin, C.-H. Tsai, Y.-S. Chen, S. K. S. Huang, Y.-Z. Tseng, and W.-P. Lien Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca2+-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban: An insight into the mechanism of atrial electrical remodeling J. Am. Coll. Cardiol., April 1, 1999; 33(5): 1231 - 1237. [Abstract] [Full Text] [PDF]
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S.-H. Lee, F.-Y. Lin, W.-C. Yu, J.-J. Cheng, P. Kuan, C.-R. Hung, M.-S. Chang, and S.-A. Chen Regional Differences in the Recovery Course of Tachycardia-Induced Changes of Atrial Electrophysiological Properties Circulation, March 9, 1999; 99(9): 1255 - 1264. [Abstract] [Full Text] [PDF]
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S. G. Priori, J. Barhanin, R. N. W. Hauer, W. Haverkamp, H. J. Jongsma, A. G. Kleber, W. J. McKenna, D. M. Roden, Y. Rudy, K. Schwartz, et al. Genetic and Molecular Basis of Cardiac Arrhythmias: Impact on Clinical Management Parts I and II Circulation, February 2, 1999; 99(4): 518 - 528. [Abstract] [Full Text] [PDF]
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S.G. Priori, J. Barhanin, R.N.W. Hauer, W. Haverkamp, H.J. Jongsma, A.G. Kleber, W.J. McKenna, D.M. Roden, Y. Rudy, K. Schwartz, et al. Genetic and molecular basis of cardiac arrhythmias: Impact on clinical management Eur. Heart J., February 1, 1999; 20(3): 174 - 195. [PDF]
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C.J. Meurling, M.P. Ingemansson, A. Roijer, J. Carlson, C.J. Lindholm, B. Smideberg, L. Sorno, M. Stridh, and S.B. Olsson Attenuation of electrical remodelling in chronic atrial fibrillation following oral treatment with verapamil Europace, January 1, 1999; 1(4): 234 - 241. [Abstract] [PDF]
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C. Pandozi, L. Bianconi, M. Villani, G. Gentilucci, A. Castro, G. Altamura, A. P. Jesi, F. Lamberti, F. Ammirati, and M. Santini Electrophysiological Characteristics of the Human Atria After Cardioversion of Persistent Atrial Fibrillation Circulation, December 22, 1998; 98(25): 2860 - 2865. [Abstract] [Full Text] [PDF]
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M P Ingemansson, M Holm, and S B Olsson Autonomic modulation of the atrial cycle length by the head up tilt test: non-invasive evaluation in patients with chronic atrial fibrillation Heart, July 1, 1998; 80(1): 71 - 76. [Abstract] [Full Text]
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W.-C. Yu, S.-A. Chen, S.-H. Lee, C.-T. Tai, A.-N. Feng, B. I.-T. Kuo, Y.-A. Ding, and M.-S. Chang Tachycardia-Induced Change of Atrial Refractory Period in Humans : Rate Dependency and Effects of Antiarrhythmic Drugs Circulation, June 16, 1998; 97(23): 2331 - 2337. [Abstract] [Full Text] [PDF]
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S. Nattel, L. Liu, and D. St-Georges Effects of the novel antiarrhythmic agent azimilide on experimental atrial fibrillation and atrial electrophysiologic properties Cardiovasc Res, March 1, 1998; 37(3): 627 - 635. [Abstract] [Full Text] [PDF]
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R. Gaspo, R. F. Bosch, E. Bou-Abboud, and S. Nattel Tachycardia-Induced Changes in Na+ Current in a Chronic Dog Model of Atrial Fibrillation Circ. Res., December 19, 1997; 81(6): 1045 - 1052. [Abstract] [Full Text]
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M. C. E. F. Wijffels, C. J. H. J. Kirchhof, R. Dorland, J. Power, and M. A. Allessie Electrical Remodeling due to Atrial Fibrillation in Chronically Instrumented Conscious Goats : Roles of Neurohumoral Changes, Ischemia, Atrial Stretch, and High Rate of Electrical Activation Circulation, November 18, 1997; 96(10): 3710 - 3720. [Abstract] [Full Text]
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D. P. Zipes Electrophysiological Remodeling of the Heart Owing to Rate Circulation, April 1, 1997; 95(7): 1745 - 1748. [Full Text]
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