This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gómez, A.M. Articles by Lederer, W.J. Search for Related Content PubMed PubMed Citation Articles by Gómez, A.M. Articles by Lederer, W.J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL OUABAIN TETRODOTOXIN Medline Plus Health Information Heart Attack Heart Failure Related Collections Animal models of human disease Calcium cycling/excitation-contraction coupling Heart failure - basic studies

(Circulation. 2001;104:688.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Heart Failure After Myocardial Infarction

Altered Excitation-Contraction Coupling

A.M. Gómez, PhD; S. Guatimosim, PhD; K.W. Dilly, PhD; G. Vassort, PhD; W.J. Lederer, MD, PhD

From INSERM-U.390, IFR-3, Montpellier, France (A.M.G., G.V.), and Medical Biotechnology Center and School of Medicine, University of Maryland Biotechnology Institute, Baltimore (A.M.G., S.G., K.W.D., W.J.L.).

Correspondence to A.M. 8Gómez, INSERM-U.390, CHU Arnaud de Villeneuve, 34295 Montpellier, France. E-mail agomez{at}montp.inserm.fr

Background—— Heart failure (HF) frequently follows the occurrence of myocardial infarction (MI). Questions about how HF develops and what cellular defects contribute to this dysfunction led to this study.

Methods and Results—— MI was induced in rats by coronary artery ligation. Clinical examination of the post-MI (PMI) surviving animals indicated that they were in overt HF by all measures. Cellular examination of the cardiomyocytes by patch-clamp and confocal [Ca²⁺]_i imaging methods indicated that cellular function was significantly compromised. At the single-cell level, [Ca²⁺]_i transient amplitudes were reduced and contractions were decreased and slowed, although Ca²⁺ current (I_Ca) remained unchanged. The excitation-contraction coupling (ECC) gain function measured as [Ca²⁺]_i/I_Ca was significantly decreased. Ouabain, a cardiotonic steroid that blocks the Na⁺,K⁺-ATPase and activates Ca²⁺ entry via cardiac Na⁺ channels, largely alleviated this defect.

Conclusions—— After MI, I_Ca becomes less able to trigger release of Ca²⁺ from the sarcoplasmic reticulum. This failure of ECC is a major factor contributing to the development of contractile dysfunction and HF in PMI animals. The improved ECC gain, enhanced Ca²⁺ entry, and augmented Ca²⁺ signaling due to cardiotonic steroids contribute to the beneficial effects of these agents.

Key Words: excitation • myocardial infarction • ouabain • heart failure • calcium

This article has been cited by other articles:

				M. Maczewski and U. Mackiewicz Effect of metoprolol and ivabradine on left ventricular remodelling and Ca2+ handling in the post-infarction rat heart Cardiovasc Res, July 1, 2008; 79(1): 42 - 51. [Abstract] [Full Text] [PDF]

				M. Guazzi, R. Arena, and M. D. Guazzi Evolving changes in lung interstitial fluid content after acute myocardial infarction: mechanisms and pathophysiological correlates Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1357 - H1364. [Abstract] [Full Text] [PDF]

				F. R. Heinzel, V. Bito, L. Biesmans, M. Wu, E. Detre, F. von Wegner, P. Claus, S. Dymarkowski, F. Maes, J. Bogaert, et al. Remodeling of T-Tubules and Reduced Synchrony of Ca2+ Release in Myocytes From Chronically Ischemic Myocardium Circ. Res., February 15, 2008; 102(3): 338 - 346. [Abstract] [Full Text] [PDF]

				C. Orchard and F. Brette t-tubules and sarcoplasmic reticulum function in cardiac ventricular myocytes Cardiovasc Res, January 15, 2008; 77(2): 237 - 244. [Abstract] [Full Text] [PDF]

				V. Bito, F. R. Heinzel, L. Biesmans, G. Antoons, and K. R. Sipido Crosstalk between L-type Ca2+ channels and the sarcoplasmic reticulum: alterations during cardiac remodelling Cardiovasc Res, January 15, 2008; 77(2): 315 - 324. [Abstract] [Full Text] [PDF]

				S. E. Lehnart, M. J. Ackerman, D. W. Benson Jr, R. Brugada, C. E. Clancy, J. K. Donahue, A. L. George Jr, A. O. Grant, S. C. Groft, C. T. January, et al. Inherited Arrhythmias: A National Heart, Lung, and Blood Institute and Office of Rare Diseases Workshop Consensus Report About the Diagnosis, Phenotyping, Molecular Mechanisms, and Therapeutic Approaches for Primary Cardiomyopathies of Gene Mutations Affecting Ion Channel Function Circulation, November 13, 2007; 116(20): 2325 - 2345. [Abstract] [Full Text] [PDF]

				K. M. Shioura, D. L. Geenen, and P. H. Goldspink Assessment of cardiac function with the pressure-volume conductance system following myocardial infarction in mice Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2870 - H2877. [Abstract] [Full Text] [PDF]

				F. Brette and C. Orchard Resurgence of Cardiac T-Tubule Research Physiology, June 1, 2007; 22(3): 167 - 173. [Abstract] [Full Text] [PDF]

				J. R. Wilding, F. Joubert, C. de Araujo, D. Fortin, M. Novotova, V. Veksler, and R. Ventura-Clapier Altered energy transfer from mitochondria to sarcoplasmic reticulum after cytoarchitectural perturbations in mice hearts J. Physiol., August 15, 2006; 575(1): 191 - 200. [Abstract] [Full Text] [PDF]

				W. E. Louch, H. K. Mork, J. Sexton, T. A. Stromme, P. Laake, I. Sjaastad, and O. M. Sejersted T-tubule disorganization and reduced synchrony of Ca2+ release in murine cardiomyocytes following myocardial infarction J. Physiol., July 15, 2006; 574(2): 519 - 533. [Abstract] [Full Text] [PDF]

				X. Koh, B. Srinivasan, H. S. Ching, and A. Levchenko A 3D Monte Carlo Analysis of the Role of Dyadic Space Geometry in Spark Generation Biophys. J., March 15, 2006; 90(6): 1999 - 2014. [Abstract] [Full Text] [PDF]

				L.-S. Song, E. A. Sobie, S. McCulle, W. J. Lederer, C. W. Balke, and H. Cheng Orphaned ryanodine receptors in the failing heart. PNAS, March 14, 2006; 103(11): 4305 - 4310. [Abstract] [Full Text] [PDF]

				C. Pott, K. D. Philipson, and J. I. Goldhaber Excitation-Contraction Coupling in Na+-Ca2+ Exchanger Knockout Mice: Reduced Transsarcolemmal Ca2+ Flux Circ. Res., December 9, 2005; 97(12): 1288 - 1295. [Abstract] [Full Text] [PDF]

				K. R. Sipido and D. Eisner Something old, something new: Changing views on the cellular mechanisms of heart failure Cardiovasc Res, November 1, 2005; 68(2): 167 - 174. [Full Text] [PDF]

				R. M. Guzzo, M. Salih, E. D. Moore, and B. S. Tuana Molecular properties of cardiac tail-anchored membrane protein SLMAP are consistent with structural role in arrangement of excitation-contraction coupling apparatus Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1810 - H1819. [Abstract] [Full Text] [PDF]

				K. W. Chaudhary, E. I. Rossman, V. Piacentino III, A. Kenessey, C. Weber, J. P. Gaughan, K. Ojamaa, I. Klein, D. M. Bers, S. R. Houser, et al. Altered myocardial Ca2+ cycling after left ventricular assist device support in the failing human heart J. Am. Coll. Cardiol., August 18, 2004; 44(4): 837 - 845. [Abstract] [Full Text] [PDF]

				E. Perrier, B.-G. Kerfant, N. Lalevee, P. Bideaux, M. F. Rossier, S. Richard, A. M. Gomez, and J.-P. Benitah Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction Circulation, August 17, 2004; 110(7): 776 - 783. [Abstract] [Full Text] [PDF]

				A. Yatani, S.-J. Kim, R. K. Kudej, Q. Wang, C. Depre, K. Irie, E. G. Kranias, S. F. Vatner, and D. E. Vatner Insights into cardioprotection obtained from study of cellular Ca2+ handling in myocardium of true hibernating mammals Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2219 - H2228. [Abstract] [Full Text] [PDF]

				G. Heusch and K. R. Sipido Myocardial Hibernation: A Double-Edged Sword Circ. Res., April 30, 2004; 94(8): 1005 - 1007. [Full Text] [PDF]

				V. E. Bondarenko, G. C. L. Bett, and R. L. Rasmusson A model of graded calcium release and L-type Ca2+ channel inactivation in cardiac muscle Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1154 - H1169. [Abstract] [Full Text] [PDF]

				T. Zhang, S. Miyamoto, and J. H. Brown Cardiomyocyte Calcium and Calcium/Calmodulin-dependent Protein Kinase II: Friends or Foes? Recent Prog. Horm. Res., January 1, 2004; 59(1): 141 - 168. [Abstract] [Full Text]

				M. Zheng, K. Dilly, J. Dos Santos Cruz, M. Li, Y. Gu, J. A. Ursitti, J. Chen, J. Ross Jr., K. R. Chien, J. W. Lederer, et al. Sarcoplasmic reticulum calcium defect in Ras-induced hypertrophic cardiomyopathy heart Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H424 - H433. [Abstract] [Full Text] [PDF]

				B. C. Linden, E. R. Resnik, K. J. Hendrickson, J. M. Herron, T. J. O'Connor, and D. N. Cornfield Chronic intrauterine pulmonary hypertension compromises fetal pulmonary artery smooth muscle cell O2 sensing Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1354 - L1361. [Abstract] [Full Text] [PDF]

				F. Brette and C. Orchard T-Tubule Function in Mammalian Cardiac Myocytes Circ. Res., June 13, 2003; 92(11): 1182 - 1192. [Abstract] [Full Text] [PDF]

				M.E. Diaz, D.A. Eisner, and S.C. O'Neill Depressed Ryanodine Receptor Activity Increases Variability and Duration of the Systolic Ca2+ Transient in Rat Ventricular Myocytes Circ. Res., October 4, 2002; 91(7): 585 - 593. [Abstract] [Full Text] [PDF]

				S. Q. Wang, E. G. Lakatta, H. Cheng, and Z. Q. Zhou Adaptive mechanisms of intracellular calcium homeostasis in mammalian hibernators J. Exp. Biol., October 1, 2002; 205(19): 2957 - 2962. [Abstract] [Full Text] [PDF]

				I. Sjaastad, J. Bokenes, F. Swift, J. A. Wasserstrom, and O. M. Sejersted Normal contractions triggered by ICa,L in ventricular myocytes from rats with postinfarction CHF Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1225 - H1236. [Abstract] [Full Text] [PDF]

				A. M. Gomez, B. Schwaller, H. Porzig, G. Vassort, E. Niggli, and M. Egger Increased Exchange Current but Normal Ca2+ Transport via Na+-Ca2+ Exchange During Cardiac Hypertrophy After Myocardial Infarction Circ. Res., August 23, 2002; 91(4): 323 - 330. [Abstract] [Full Text] [PDF]