Repolarization abnormalities, arrhythmia and sudden death in canine tachycardia-induced cardiomyopathy

Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. peterpak@welchlink.welch.jhu.edu

OBJECTIVES: This study sought to determine whether the canine model of tachycardia-induced heart failure (HF) is an effective model for sudden cardiac death (SCD) in HF. BACKGROUND: Such a well established HF model that also exhibits arrhythmias and SCD, along with repolarization abnormalities that could trigger them, may facilitate the study of SCD in HF, which still eludes effective treatment. METHODS: Twenty-five dogs were VVI-paced at 250 beats/min for 3 to 5 weeks. Electrocardiograms were obtained, and left ventricular endocardial monophasic action potentials (MAPs) were recorded at six sites at baseline and after HF. Weekly Holter recordings were made with pacing suspended for 24 h. RESULTS: Six animals (24%) died suddenly, one with Holter-documented polymorphic ventricular tachycardia (VT). Holter recordings revealed an increased incidence of VT as HF progressed. Repolarization was significantly (p < 0.05) prolonged, as indexed by a corrected QT interval (mean [+/-SD] 311 +/- 25 to 338 +/- 25 ms) and MAP duration measured at 90% repolarization (MAPD90) (181 +/- 19 to 209 +/- 28 ms), and spatial MAPD90 dispersion rose by 40%. We further tested whether CsCl inhibition of repolarizing K+ currents, which are reportedly downregulated in HF, might preferentially prolong the MAPD90 in HF. With 1 mEq/kg body weight of CsCl, MAPD90 rose by 86 +/- 100 ms in dogs with HF versus only 28 +/- 16 ms in control animals (p = 0.002). Similar disparities in CsCl sensitivity were observed in myocytes isolated from normal and failing hearts. CONCLUSIONS: Tachycardia-induced HF exhibits malignant arrhythmia and SCD, along with prolonged, heterogeneous repolarization and heightened sensitivity to CsCl at chamber and cellular levels. Thus, it appears to be a useful model for studying mechanisms and therapy of SCD in HF.

This article has been cited by other articles:

				A. Maguy, S. Le Bouter, P. Comtois, D. Chartier, L. Villeneuve, R. Wakili, K. Nishida, and S. Nattel Ion Channel Subunit Expression Changes in Cardiac Purkinje Fibers: A Potential Role in Conduction Abnormalities Associated With Congestive Heart Failure Circ. Res., May 8, 2009; 104(9): 1113 - 1122. [Abstract] [Full Text] [PDF]

				H. L. Lujan, Y. Chen, and S. E. DiCarlo Paraplegia increased cardiac NGF content, sympathetic tonus, and the susceptibility to ischemia-induced ventricular tachycardia in conscious rats Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1364 - H1372. [Abstract] [Full Text] [PDF]

				T. Aiba, G. G. Hesketh, A. S. Barth, T. Liu, S. Daya, K. Chakir, V. L. Dimaano, T. P. Abraham, B. O'Rourke, F. G. Akar, et al. Electrophysiological Consequences of Dyssynchronous Heart Failure and Its Restoration by Resynchronization Therapy Circulation, March 10, 2009; 119(9): 1220 - 1230. [Abstract] [Full Text] [PDF]

				Z. Gao, A. S. Barth, D. DiSilvestre, F. G. Akar, Y. Tian, A. Tanskanen, D. A. Kass, R. L. Winslow, and G. F. Tomaselli Key pathways associated with heart failure development revealed by gene networks correlated with cardiac remodeling Physiol Genomics, November 12, 2008; 35(3): 222 - 230. [Abstract] [Full Text] [PDF]

				G. Laurent, G. Moe, X. Hu, H. Leong-Poi, K. A. Connelly, P. P.-S. So, A. Ramadeen, L. Doumanovskaia, A. Konig, J. Trogadis, et al. Experimental studies of atrial fibrillation: a comparison of two pacing models Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1206 - H1215. [Abstract] [Full Text] [PDF]

				A. A. Armoundas, J. Rose, R. Aggarwal, B. D. Stuyvers, B. O'Rourke, D. A. Kass, E. Marban, S. R. Shorofsky, G. F. Tomaselli, and C. William Balke Cellular and molecular determinants of altered Ca2+ handling in the failing rabbit heart: primary defects in SR Ca2+ uptake and release mechanisms Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1607 - H1618. [Abstract] [Full Text] [PDF]

				Y. Tsuji, S. Zicha, X.-Y. Qi, I. Kodama, and S. Nattel Potassium Channel Subunit Remodeling in Rabbits Exposed to Long-Term Bradycardia or Tachycardia: Discrete Arrhythmogenic Consequences Related to Differential Delayed-Rectifier Changes Circulation, January 24, 2006; 113(3): 345 - 355. [Abstract] [Full Text] [PDF]

				V. S. Chauhan, E. Downar, K. Nanthakumar, J. D. Parker, H. J. Ross, W. Chan, and P. Picton Increased ventricular repolarization heterogeneity in patients with ventricular arrhythmia vulnerability and cardiomyopathy: a human in vivo study Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H79 - H86. [Abstract] [Full Text] [PDF]

				M. Shah, F. G. Akar, and G. F. Tomaselli Molecular Basis of Arrhythmias Circulation, October 18, 2005; 112(16): 2517 - 2529. [Abstract] [Full Text] [PDF]

				W. Xiong, Y. Tian, D. DiSilvestre, and G. F. Tomaselli Transmural Heterogeneity of Na+-Ca2+ Exchange: Evidence for Differential Expression in Normal and Failing Hearts Circ. Res., August 5, 2005; 97(3): 207 - 209. [Abstract] [Full Text] [PDF]

				F. G. Akar, R. C. Wu, G. J. Juang, Y. Tian, M. Burysek, D. DiSilvestre, W. Xiong, A. A. Armoundas, and G. F. Tomaselli Molecular mechanisms underlying K+ current downregulation in canine tachycardia-induced heart failure Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2887 - H2896. [Abstract] [Full Text] [PDF]

				J. Rose, A. A. Armoundas, Y. Tian, D. DiSilvestre, M. Burysek, V. Halperin, B. O'Rourke, D. A. Kass, E. Marban, and G. F. Tomaselli Molecular correlates of altered expression of potassium currents in failing rabbit myocardium Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2077 - H2087. [Abstract] [Full Text] [PDF]

				D. M. Harris, G. D. Mills, X. Chen, H. Kubo, R. M. Berretta, V. S. Votaw, L. F. Santana, and S. R. Houser Alterations in Early Action Potential Repolarization Causes Localized Failure of Sarcoplasmic Reticulum Ca2+ Release Circ. Res., March 18, 2005; 96(5): 543 - 550. [Abstract] [Full Text] [PDF]

				E. Vanoli, S. Bacchini, S. Panigada, F. Pentimalli, and P. B Adamson Experimental models of heart failure Eur. Heart J. Suppl., November 1, 2004; 6(suppl_F): F7 - F15. [Abstract] [Full Text] [PDF]

				P. Nerheim, S. Birger-Botkin, L. Piracha, and B. Olshansky Heart Failure and Sudden Death in Patients With Tachycardia-Induced Cardiomyopathy and Recurrent Tachycardia Circulation, July 20, 2004; 110(3): 247 - 252. [Abstract] [Full Text] [PDF]

				R. Cardinal, G. Rousseau, C. Bouchard, M. Vermeulen, J.-G. Latour, and P. L. Page Myocardial electrical alteration in canine preparations with combined chronic rapid pacing and progressive coronary artery occlusion Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1496 - H1506. [Abstract] [Full Text] [PDF]

				M. J Janse Electrophysiological changes in heart failure and their relationship to arrhythmogenesis Cardiovasc Res, February 1, 2004; 61(2): 208 - 217. [Abstract] [Full Text] [PDF]

				F. G. Akar and D. S. Rosenbaum Transmural Electrophysiological Heterogeneities Underlying Arrhythmogenesis in Heart Failure Circ. Res., October 3, 2003; 93(7): 638 - 645. [Abstract] [Full Text] [PDF]

				N. Paolocci, T. Katori, H. C. Champion, M. E. St. John, K. M. Miranda, J. M. Fukuto, D. A. Wink, and D. A. Kass From the Cover: Positive inotropic and lusitropic effects of HNO/NO- in failing hearts: Independence from beta -adrenergic signaling PNAS, April 29, 2003; 100(9): 5537 - 5542. [Abstract] [Full Text] [PDF]

				S. Kaab, M. Hinterseer, M. Nabauer, and G. Steinbeck Sotalol testing unmasks altered repolarization in patients with suspected acquired long-QT-syndrome--a case-control pilot study using i.v. sotalol Eur. Heart J., April 1, 2003; 24(7): 649 - 657. [Abstract] [Full Text] [PDF]

				G.-R. Li, C.-P. Lau, A. Ducharme, J.-C. Tardif, and S. Nattel Transmural action potential and ionic current remodeling in ventricles of failing canine hearts Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1031 - H1041. [Abstract] [Full Text] [PDF]

				Y. Matsumoto, H. Aihara, R. Yamauchi-Kohno, Y. Reien, T. Ogura, H. Yabana, Y. Masuda, T. Sato, I. Komuro, and H. Nakaya Long-Term Endothelin A Receptor Blockade Inhibits Electrical Remodeling in Cardiomyopathic Hamsters Circulation, July 30, 2002; 106(5): 613 - 619. [Abstract] [Full Text] [PDF]

				G. J. Rozanski and Z. Xu Glutathione and K+ channel remodeling in postinfarction rat heart Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2346 - H2355. [Abstract] [Full Text] [PDF]

				D. Lacroix, P. Gluais, C. Marquie, C. D'Hoinne, M. Adamantidis, and M. Bastide Repolarization abnormalities and their arrhythmogenic consequences in porcine tachycardia-induced cardiomyopathy Cardiovasc Res, April 1, 2002; 54(1): 42 - 50. [Abstract] [Full Text] [PDF]

				L.-M. Zhang, Z. Wang, and S. Nattel Effects of sustained beta -adrenergic stimulation on ionic currents of cultured adult guinea pig cardiomyocytes Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H880 - H889. [Abstract] [Full Text] [PDF]

				K. R Sipido, P. G.A Volders, M. A Vos, and F. Verdonck Altered Na/Ca exchange activity in cardiac hypertrophy and heart failure: a new target for therapy? Cardiovasc Res, March 1, 2002; 53(4): 782 - 805. [Abstract] [Full Text] [PDF]

				T. Watanabe, M. Yamaki, S. Yamauchi, O. Minamihaba, T. Miyashita, I. Kubota, and H. Tomoike Regional prolongation of ARI and altered restitution properties cause ventricular arrhythmia in heart failure Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H212 - H218. [Abstract] [Full Text] [PDF]

				W. Han, D. Chartier, D. Li, and S. Nattel Ionic Remodeling of Cardiac Purkinje Cells by Congestive Heart Failure Circulation, October 23, 2001; 104(17): 2095 - 2100. [Abstract] [Full Text] [PDF]

				R. N. Ghanem, J. E. Burnes, A. L. Waldo, and Y. Rudy Imaging Dispersion of Myocardial Repolarization, II: Noninvasive Reconstruction of Epicardial Measures Circulation, September 11, 2001; 104(11): 1306 - 1312. [Abstract] [Full Text] [PDF]

				S. Kaab and M. Nabauer Diversity of ion channel expression in health and disease Eur. Heart J. Suppl., September 1, 2001; 3(suppl_K): K31 - K40. [Abstract] [PDF]

				C. A. Ufret-Vincenty, D. J. Baro, and L. F. Santana Differential contribution of sialic acid to the function of repolarizing K+ currents in ventricular myocytes Am J Physiol Cell Physiol, August 1, 2001; 281(2): C464 - C474. [Abstract] [Full Text] [PDF]

				J.M van Opstal, S.C Verduyn, H.D.M Leunissen, S.H.M de Groot, H.J.J Wellens, and M.A Vos Electrophysiological parameters indicative of sudden cardiac death in the dog with chronic complete AV-block Cardiovasc Res, May 1, 2001; 50(2): 354 - 361. [Abstract] [Full Text] [PDF]

				P.-S. Chen, L. S Chen, J.-M. Cao, B. Sharifi, H. S Karagueuzian, and M. C Fishbein Sympathetic nerve sprouting, electrical remodeling and the mechanisms of sudden cardiac death Cardiovasc Res, May 1, 2001; 50(2): 409 - 416. [Abstract] [Full Text] [PDF]

				S. S. Chugh, J. L. Blackshear, W.-K. Shen, S. C. Hammill, and B. J. Gersh Epidemiology and natural history of atrial fibrillation: clinical implications J. Am. Coll. Cardiol., February 1, 2001; 37(2): 371 - 378. [Abstract] [Full Text] [PDF]

				K. Kataoka, R. Nohara, R. Hosokawa, T. Hirai, K. Okuda, C. Li-Guang, Y. Fujibayashi, M. Fujita, J. Konishi, and S. Sasayama Myocardial Lipid Metabolism in Compensated and Advanced Stages of Heart Failure: Evaluation by Canine Pacing Model with BMIPP J. Nucl. Med., January 1, 2001; 42(1): 124 - 129. [Abstract] [Full Text] [PDF]

				S. S. Chugh, S. B. Johnson, and D. L. Packer Altered response to ibutilide in a heart failure model Cardiovasc Res, January 1, 2001; 49(1): 94 - 102. [Abstract] [Full Text] [PDF]

				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]

				S. Nattel Acquired delayed rectifier channelopathies: how heart disease and antiarrhythmic drugs mimic potentially-lethal congenital cardiac disorders Cardiovasc Res, November 1, 2000; 48(2): 188 - 190. [Full Text] [PDF]

				Y. Tsuji, T. Opthof, K. Kamiya, K. Yasui, W. Liu, Z. Lu, and I. Kodama Pacing-induced heart failure causes a reduction of delayed rectifier potassium currents along with decreases in calcium and transient outward currents in rabbit ventricle Cardiovasc Res, November 1, 2000; 48(2): 300 - 309. [Abstract] [Full Text] [PDF]

				S. H. M. de Groot, M. Schoenmakers, M. M. C. Molenschot, J. D. M. Leunissen, H. J. J. Wellens, and M. A. Vos Contractile Adaptations Preserving Cardiac Output Predispose the Hypertrophied Canine Heart to Delayed Afterdepolarization-Dependent Ventricular Arrhythmias Circulation, October 24, 2000; 102(17): 2145 - 2151. [Abstract] [Full Text] [PDF]

				W. Han, Z. Wang, and S. Nattel A comparison of transient outward currents in canine cardiac Purkinje cells and ventricular myocytes Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H466 - H474. [Abstract] [Full Text] [PDF]

				J.-M. Cao, L. S. Chen, B. H. KenKnight, T. Ohara, M.-H. Lee, J. Tsai, W. W. Lai, H. S. Karagueuzian, P. L. Wolf, M. C. Fishbein, et al. Nerve Sprouting and Sudden Cardiac Death Circ. Res., April 14, 2000; 86(7): 816 - 821. [Abstract] [Full Text] [PDF]

				H. B. Nuss, S. Kaab, D. A. Kass, G. F. Tomaselli, and E. Marban Cellular basis of ventricular arrhythmias and abnormal automaticity in heart failure Am J Physiol Heart Circ Physiol, July 1, 1999; 277(1): H80 - H91. [Abstract] [Full Text] [PDF]

				G. F. Tomaselli and E. Marban Electrophysiological remodeling in hypertrophy and heart failure Cardiovasc Res, May 1, 1999; 42(2): 270 - 283. [Full Text] [PDF]

				G. Hasenfuss Animal models of human cardiovascular disease, heart failure and hypertrophy Cardiovasc Res, July 1, 1998; 39(1): 60 - 76. [Abstract] [Full Text] [PDF]

				M. Nabauer and S. Kaab Potassium channel down-regulation in heart failure Cardiovasc Res, February 1, 1998; 37(2): 324 - 334. [Abstract] [Full Text] [PDF]

				C. A. Ufret-Vincenty, D. J. Baro, W. J. Lederer, H. A. Rockman, L. E. Quinones, and L. F. Santana Role of Sodium Channel Deglycosylation in the Genesis of Cardiac Arrhythmias in Heart Failure J. Biol. Chem., July 20, 2001; 276(30): 28197 - 28203. [Abstract] [Full Text] [PDF]

				G. J. Rozanski and Z. Xu Glutathione and K+ channel remodeling in postinfarction rat heart Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2346 - H2355. [Abstract] [Full Text] [PDF]