Circulation Research. 2004;94:1083-1090
Published online before print March 11, 2004, doi: 10.1161/01.RES.0000125629.72053.95
Published online before print March 11, 2004, doi: 10.1161/01.RES.0000125629.72053.95
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2004 American Heart Association, Inc.
Cellular Biology |
Role of Calcium Cycling Versus Restitution in the Mechanism of Repolarization Alternans
From the Heart and Vascular Research Center and the Department of Biomedical Engineering, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio.
Correspondence to Kenneth R. Laurita, PhD, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Dr, Rammelkamp, 6th Floor, Cleveland, OH 44109-1998. E-mail klaurita{at}metrohealth.org
T-wave alternans, a powerful marker of arrhythmic events, results from alternation in action potential duration (APD). The underlying cellular mechanism of APD alternans is unknown but has been attributed to either intracellular calcium (Ca2+) cycling or membrane ionic currents, manifested by a steep slope of cellular APD restitution. To address these mechanisms, high-resolution optical mapping techniques were used to measure action potentials and Ca2+ transients simultaneously from hundreds of epicardial sites in the guinea pig model of pacing-induced T-wave alternans (n=7). The pacing rates (ie, alternans threshold) at which T-wave (369±11 bpm), APD (369±21 bpm), and Ca2+ (371±29 bpm) alternans first appeared were comparable. Importantly, the site of origin of APD alternans and Ca2+ alternans consistently occurred together near the base of the left ventricle, not where APD restitution was steepest. In addition, APD and Ca2+ alternans were remarkably similar both spatially and temporally during discordant alternans. In conclusion, the mechanism underlying T-wave alternans in the intact heart is more closely associated with intracellular Ca2+ cycling rather than APD restitution.
Key Words: electrophysiology • T-wave alternans • repolarization • Ca2+ cycling • optical mapping
This article has been cited by other articles:
 |
|
 |
|
  J. A. Wasserstrom, R. Sharma, M. J. O'Toole, J. Zheng, J. E. Kelly, J. Shryock, L. Belardinelli, and G. L. Aistrup Ranolazine Antagonizes the Effects of Increased Late Sodium Current on Intracellular Calcium Cycling in Rat Isolated Intact Heart J. Pharmacol. Exp. Ther., November 1, 2009; 331(2): 382 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Morita, A. A. Sovari, Y. Xie, M. C. Fishbein, W. J. Mandel, A. Garfinkel, S.-F. Lin, P.-S. Chen, L.-H. Xie, F. Chen, et al. Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1594 - H1605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Ziv, E. Morales, Y.-k. Song, X. Peng, K. E. Odening, A. E. Buxton, A. Karma, G. Koren, and B.-R. Choi Origin of complex behaviour of spatially discordant alternans in a transgenic rabbit model of type 2 long QT syndrome J. Physiol., October 1, 2009; 587(19): 4661 - 4680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-H. Xie and J. N. Weiss Arrhythmogenic consequences of intracellular calcium waves Am J Physiol Heart Circ Physiol, September 1, 2009; 297(3): H997 - H1002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Gaeta, G. Bub, G. W. Abbott, and D. J. Christini Dynamical Mechanism for Subcellular Alternans in Cardiac Myocytes Circ. Res., August 14, 2009; 105(4): 335 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Wasserstrom, R. Sharma, S. Kapur, J. E. Kelly, A. H. Kadish, C. W. Balke, and G. L. Aistrup Multiple Defects in Intracellular Calcium Cycling in Whole Failing Rat Heart Circ Heart Fail, May 1, 2009; 2(3): 223 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Keldermann, K. H. W. J. ten Tusscher, M. P. Nash, C. P. Bradley, R. Hren, P. Taggart, and A. V. Panfilov A computational study of mother rotor VF in the human ventricles Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H370 - H379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tao, S. C. O'Neill, M. E. Diaz, Y. T. Li, D. A. Eisner, and H. Zhang Alternans of cardiac calcium cycling in a cluster of ryanodine receptors: a simulation study Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H598 - H609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Guo, L. Young, C. Patel, Z. Jiao, Y. Wu, T. Liu, P. R. Kowey, and G.-X. Yan Calcium-activated chloride current contributes to action potential alternations in left ventricular hypertrophy rabbit Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H97 - H104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Stambler and K. R. Laurita Atrial Fibrillation in Heart Failure: Steady Progress but Still a Long Way to Go Circ Arrhythm Electrophysiol, June 1, 2008; 1(2): 77 - 79. [Full Text] [PDF]
|
|
|
|
|
|
R. H. Keldermann, K. H. W. J. ten Tusscher, M. P. Nash, R. Hren, P. Taggart, and A. V. Panfilov Effect of heterogeneous APD restitution on VF organization in a model of the human ventricles Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H764 - H774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. T. Clusin Mechanisms of calcium transient and action potential alternans in cardiac cells and tissues Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H1 - H10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Kjolbye, M. Dikshteyn, B. C. Eloff, I. Deschenes, and D. S. Rosenbaum Maintenance of intercellular coupling by the antiarrhythmic peptide rotigaptide suppresses arrhythmogenic discordant alternans Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H41 - H49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. de Diego, F. Chen, L.-H. Xie, A. S. Dave, M. Thu, C. Rongey, J. N. Weiss, and M. Valderrabano Cardiac alternans in embryonic mouse ventricles Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H433 - H440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Narayan, M. R. Franz, G. Lalani, J. Kim, and A. Sastry T-Wave Alternans, Restitution of Human Action Potential Duration, and Outcome J. Am. Coll. Cardiol., December 18, 2007; 50(25): 2385 - 2392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Wilson and D. S. Rosenbaum Mechanisms of arrythmogenic cardiac alternans Europace, November 1, 2007; 9(suppl_6): vi77 - vi82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Pruvot, F. Jousset, P. Ruchat, J.-M. Vesin, Y. Prudat, T. Zerm, and M. Fromer Propagation velocity kinetics and repolarization alternans in a free-behaving sheep model of pacing-induced atrial fibrillation Europace, November 1, 2007; 9(suppl_6): vi83 - vi88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. N. Jordan and D. J. Christini Characterizing the contribution of voltage- and calcium-dependent coupling to action potential stability: implications for repolarization alternans Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2109 - H2118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Iravanian and D. J. Christini Optical mapping system with real-time control capability Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2605 - H2611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Y. Kim, S.-J. Woo, S.-m. Hwang, J. H. Hong, and K. J. Lee Cardiac beat-to-beat alternations driven by unusual spiral waves PNAS, July 10, 2007; 104(28): 11639 - 11642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Livshitz and Y. Rudy Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2854 - H2866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Huffaker, J. N. Weiss, and B. Kogan Effects of early afterdepolarizations on reentry in cardiac tissue: a simulation study Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3089 - H3102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-C. Chou, S. Zhou, H. Hayashi, M. Nihei, Y.-B. Liu, M.-S. Wen, S.-J. Yeh, M. C. Fishbein, J. N. Weiss, S.-F. Lin, et al. Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts J. Physiol., May 1, 2007; 580(3): 895 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Katra, T. Oya, G. S. Hoeker, and K. R. Laurita Ryanodine receptor dysfunction and triggered activity in the heart Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2144 - H2151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. D. J. ter Keurs and P. A. Boyden Calcium and Arrhythmogenesis Physiol Rev, April 1, 2007; 87(2): 457 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Pitruzzello, W. Krassowska, and S. F. Idriss Spatial heterogeneity of the restitution portrait in rabbit epicardium Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1568 - H1578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Ng, K. E. Brack, V. H. Patel, and J. H. Coote Autonomic modulation of electrical restitution, alternans and ventricular fibrillation initiation in the isolated heart Cardiovasc Res, March 1, 2007; 73(4): 750 - 760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Selvaraj, P. Picton, K. Nanthakumar, S. Mak, and V. S. Chauhan Endocardial and Epicardial Repolarization Alternans in Human Cardiomyopathy: Evidence for Spatiotemporal Heterogeneity and Correlation With Body Surface T-Wave Alternans J. Am. Coll. Cardiol., January 23, 2007; 49(3): 338 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Thomas, M. J. Killeen, I. S. Gurung, P. Hakim, R. Balasubramaniam, C. A. Goddard, A. A. Grace, and C. L.-H. Huang Mechanisms of ventricular arrhythmogenesis in mice following targeted disruption of KCNE1 modelling long QT syndrome 5 J. Physiol., January 1, 2007; 578(1): 99 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ono, H. Hayashi, A. Kawase, S.-F. Lin, H. Li, J. N. Weiss, P.-S. Chen, and H. S. Karagueuzian Spontaneous atrial fibrillation initiated by triggered activity near the pulmonary veins in aged rats subjected to glycolytic inhibition Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H639 - H648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Coutu, D. Chartier, and S. Nattel Comparison of Ca2+-handling properties of canine pulmonary vein and left atrial cardiomyocytes Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2290 - H2300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Aistrup, J. E. Kelly, S. Kapur, M. Kowalczyk, I. Sysman-Wolpin, A. H. Kadish, and J. A. Wasserstrom Pacing-induced Heterogeneities in Intracellular Ca2+ Signaling, Cardiac Alternans, and Ventricular Arrhythmias in Intact Rat Heart Circ. Res., September 29, 2006; 99(7): E65 - E73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sato, Y. Shiferaw, A. Garfinkel, J. N. Weiss, Z. Qu, and A. Karma Spatially Discordant Alternans in Cardiac Tissue: Role of Calcium Cycling Circ. Res., September 1, 2006; 99(5): 520 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. H. W. J. ten Tusscher and A. V. Panfilov Alternans and spiral breakup in a human ventricular tissue model Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1088 - H1100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Weiss, A. Karma, Y. Shiferaw, P.-S. Chen, A. Garfinkel, and Z. Qu From Pulsus to Pulseless: The Saga of Cardiac Alternans Circ. Res., May 26, 2006; 98(10): 1244 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Iribe, P. Kohl, and D. Noble Modulatory effect of calmodulin-dependent kinase II (CaMKII) on sarcoplasmic reticulum Ca2+ handling and interval-force relations: a modelling study Phil Trans R Soc A, May 15, 2006; 364(1842): 1107 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Bian and L. Tung Structure-Related Initiation of Reentry by Rapid Pacing in Monolayers of Cardiac Cells Circ. Res., March 3, 2006; 98(4): e29 - e38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Fossa, T. Wisialowski, and K. Crimin QT Prolongation Modifies Dynamic Restitution and Hysteresis of the Beat-to-Beat QT-TQ Interval Relationship during Normal Sinus Rhythm under Varying States of Repolarization J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 498 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Narayan T-Wave Alternans and the Susceptibility to Ventricular Arrhythmias J. Am. Coll. Cardiol., January 17, 2006; 47(2): 269 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-m. Hwang, T. Y. Kim, and K. J. Lee From The Cover: Complex-periodic spiral waves in confluent cardiac cell cultures induced by localized inhomogeneities PNAS, July 19, 2005; 102(29): 10363 - 10368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Boyden and H. E.D.J. ter Keurs An Intimate Relationship: Ca2+ and Cardiac Ion Channels Circ. Res., March 4, 2005; 96(4): 393 - 394. [Full Text] [PDF]
|
|
|
|
|
|
J. I. Goldhaber, L.-H. Xie, T. Duong, C. Motter, K. Khuu, and J. N. Weiss Action Potential Duration Restitution and Alternans in Rabbit Ventricular Myocytes: The Key Role of Intracellular Calcium Cycling Circ. Res., March 4, 2005; 96(4): 459 - 466. [Abstract] [Full Text] [PDF]
|
|