Circulation Research, Vol 75, 434-442, Copyright © 1994 by American Heart Association

ARTICLES

Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium

G Hasenfuss, H Reinecke, R Studer, M Meyer, B Pieske, J Holtz, C Holubarsch, H Posival, H Just and H Drexler
Medizinische Klinik III, Universitat Freiburg, Germany.

Expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase was shown to be reduced in failing human myocardium. The functional relevance of this finding, however, is not known. We investigated the relation between myocardial function and protein levels of SR Ca(2+)-ATPase in nonfailing human myocardium (8 muscle strips from 4 hearts) and in myocardium from end-stage failing hearts with dilated (10 muscle strips from 9 hearts) or ischemic (7 muscle strips from 5 hearts) cardiomyopathy. Myocardial function was evaluated by the force- frequency relation in isometrically contracting muscle strip preparations (37 degrees C, 30 to 180 min-1). In nonfailing myocardium, twitch tension rose with increasing rates of stimulation and was 76% higher at 120 min-1 compared with 30 min-1 (P < .02). In failing myocardium, there was no significant increase in average tension at stimulation rates above 30 min-1. At 120 min-1, twitch tension was decreased by 59% (P < .05) in dilated cardiomyopathy and 76% (P < .05) in ischemic cardiomyopathy compared with nonfailing myocardium. Protein levels of SR Ca(2+)-ATPase, normalized per total protein or per myosin, were reduced by 36% (P < .02) or 32% (P < .05), respectively, in failing compared with nonfailing myocardium. SR Ca(2+)-ATPase protein levels were closely related to SR Ca2+ uptake, measured in homogenates from the same hearts (r = .70, n = 16, and P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)

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				B. Pieske, L. S. Maier, V. Piacentino III, J. Weisser, G. Hasenfuss, and S. Houser Rate Dependence of [Na+]i and Contractility in Nonfailing and Failing Human Myocardium Circulation, July 23, 2002; 106(4): 447 - 453. [Abstract] [Full Text] [PDF]

				J. Kneller, H. Sun, N. Leblanc, and S. Nattel Remodeling of Ca2+-handling by atrial tachycardia: evidence for a role in loss of rate-adaptation Cardiovasc Res, May 1, 2002; 54(2): 416 - 426. [Abstract] [Full Text] [PDF]

				C. Sumbilla, D. Lewis, T. Hammerschmidt, and G. Inesi The Slippage of the Ca2+ Pump and Its Control by Anions and Curcumin in Skeletal and Cardiac Sarcoplasmic Reticulum J. Biol. Chem., April 12, 2002; 277(16): 13900 - 13906. [Abstract] [Full Text] [PDF]

				N. R. Alpert, L. A. Mulieri, and D. Warshaw The failing human heart Cardiovasc Res, April 1, 2002; 54(1): 1 - 10. [Full Text] [PDF]

				S. Goldstein Benefits of {beta}-Blocker Therapy for Heart Failure: Weighing the Evidence Arch Intern Med, March 25, 2002; 162(6): 641 - 648. [Abstract] [Full Text] [PDF]

				J. G. Muller, Y. Isomatsu, S. V. Koushik, M. O'Quinn, L. Xu, C. S. Kappler, E. Hapke, M. R. Zile, S. J. Conway, and D. R. Menick Cardiac-Specific Expression and Hypertrophic Upregulation of the Feline Na+-Ca2+ Exchanger Gene H1-Promoter in a Transgenic Mouse Model Circ. Res., February 8, 2002; 90(2): 158 - 164. [Abstract] [Full Text] [PDF]

				J. B Sande, I. Sjaastad, I. B Hoen, J. Bokenes, T. Tonnessen, E. Holt, P. K Lunde, and G. Christensen Reduced level of serine16 phosphorylated phospholamban in the failing rat myocardium: a major contributor to reduced SERCA2 activity Cardiovasc Res, February 1, 2002; 53(2): 382 - 391. [Abstract] [Full Text] [PDF]

				G. Hasenfuss, L. S. Maier, H.-P. Hermann, C. LUers, M. HUnlich, O. Zeitz, P. M.L. Janssen, and B. Pieske Influence of Pyruvate on Contractile Performance and Ca2+ Cycling in Isolated Failing Human Myocardium Circulation, January 15, 2002; 105(2): 194 - 199. [Abstract] [Full Text] [PDF]

				U. Schotten, M. Greiser, D. Benke, K. Buerkel, B. Ehrenteidt, C. Stellbrink, J. F Vazquez-Jimenez, F. Schoendube, P. Hanrath, and M. Allessie Atrial fibrillation-induced atrial contractile dysfunction: a tachycardiomyopathy of a different sort Cardiovasc Res, January 1, 2002; 53(1): 192 - 201. [Abstract] [Full Text] [PDF]

				H. Kubo, K. B. Margulies, V. Piacentino III, J. P. Gaughan, and S. R. Houser Patients With End-Stage Congestive Heart Failure Treated With {beta}-Adrenergic Receptor Antagonists Have Improved Ventricular Myocyte Calcium Regulatory Protein Abundance Circulation, August 28, 2001; 104(9): 1012 - 1018. [Abstract] [Full Text] [PDF]

				M. L. Ogletree-Hughes, L. B. Stull, W. E. Sweet, N. G. Smedira, P. M. McCarthy, and C. S. Moravec Mechanical Unloading Restores {beta}-Adrenergic Responsiveness and Reverses Receptor Downregulation in the Failing Human Heart Circulation, August 21, 2001; 104(8): 881 - 886. [Abstract] [Full Text] [PDF]

				M. Meyer, S. U. Trost, W. F. Bluhm, H. J. Knot, E. Swanson, and W. H. Dillmann Impaired sarcoplasmic reticulum function leads to contractile dysfunction and cardiac hypertrophy Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2046 - H2052. [Abstract] [Full Text] [PDF]

				M. Periasamy Adenoviral-Mediated SERCA Gene Transfer Into Cardiac Myocytes : How Much Is Too Much? Circ. Res., March 2, 2001; 88(4): 373 - 375. [Full Text] [PDF]

				T. G. Hampton, J.-F. Wang, J. DeAngelis, I. Amende, K. D. Philipson, and J. P. Morgan Enhanced gene expression of Na+/Ca2+ exchanger attenuates ischemic and hypoxic contractile dysfunction Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2846 - H2854. [Abstract] [Full Text] [PDF]

				P. M. Heerdt, J. W. Holmes, B. Cai, A. Barbone, J. D. Madigan, S. Reiken, D. L. Lee, M. C. Oz, A. R. Marks, and D. Burkhoff Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure Circulation, November 28, 2000; 102(22): 2713 - 2719. [Abstract] [Full Text] [PDF]

				M. Cavagna, J M. O'Donnell, C. Sumbilla, G. Inesi, and M. G Klein Exogenous Ca2+-ATPase isoform effects on Ca2+ transients of embryonic chicken and neonatal rat cardiac myocytes J. Physiol., October 1, 2000; 528(1): 53 - 63. [Abstract] [Full Text] [PDF]

				P. Trouve, F. Carre, I. Belikova, C. Leclercq, T. Dakhli, L. Soufir, I. Coquard, J. Ramirez-Gil, and D. Charlemagne Na+-K+-ATPase alpha 2-isoform expression in guinea pig hearts during transition from compensation to decompensation Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1972 - H1981. [Abstract] [Full Text] [PDF]

				W. Schillinger, P. M. L. Janssen, S. Emami, S. A. Henderson, R. S. Ross, N. Teucher, O. Zeitz, K. D. Philipson, J. Prestle, and G. Hasenfuss Impaired Contractile Performance of Cultured Rabbit Ventricular Myocytes After Adenoviral Gene Transfer of Na+-Ca2+ Exchanger Circ. Res., September 29, 2000; 87(7): 581 - 587. [Abstract] [Full Text] [PDF]

				L. Rothermund, Y. M. Pinto, B. Hocher, R. Vetter, S. Leggewie, P. Ko{beta}mehl, H.-D. Orzechowski, R. Kreutz, and M. Paul Cardiac Endothelin System Impairs Left Ventricular Function in Renin-Dependent Hypertension via Decreased Sarcoplasmic Reticulum Ca2+ Uptake Circulation, September 26, 2000; 102(13): 1582 - 1588. [Abstract] [Full Text] [PDF]

				L. Sen, G. Cui, G. C. Fonarow, and H. Laks Differences in mechanisms of SR dysfunction in ischemic vs. idiopathic dilated cardiomyopathy Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H709 - H718. [Abstract] [Full Text] [PDF]

				S. D. Kim and M. R. Piano The Natriuretic Peptides: Physiology and Role in Left-Ventricular Dysfunction Biol Res Nurs, July 1, 2000; 2(1): 15 - 29. [Abstract] [PDF]

				G. Munch, B. Bolck, K. Brixius, H. Reuter, U. Mehlhorn, W. Bloch, and R. H. G. Schwinger SERCA2a activity correlates with the force-frequency relationship in human myocardium Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H1924 - H1932. [Abstract] [Full Text] [PDF]

				J.-Y. Min, T. G. Hampton, J.-F. Wang, J. DeAngelis, and J. P. Morgan Depressed tolerance to fluorocarbon-simulated ischemia in failing myocardium due to impaired [Ca2+]i modulation Am J Physiol Heart Circ Physiol, May 1, 2000; 278(5): H1446 - H1456. [Abstract] [Full Text] [PDF]