(Circulation. 1996;94:1894-1901.)
© 1996 American Heart Association, Inc.
Articles |
Creatine Kinase System in Failing and Nonfailing Human Myocardium
the NMR Laboratory for Physiological Chemistry, Cardiovascular Division, Department of Medicine (L.N., J.S.I., J.F.) and Department of Anesthesia (P.D.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; Istituto di Medicina Clinica, Universita di Padova (Italy) (L.N., P.P., A.C.P.); Cardiovascular Disease and Muscle Research Laboratories, Department of Medicine, Beth Israel Hospital and Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Mass (J.K.G.); and Laboratory of Bioenergetics, Research Center for Cardiology, Moscow, Russia (V.S.).
Correspondence to Luigino Nascimben, MD, NMR Laboratory for Physiological Chemistry, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA 02115. E-mail luigin@bustoff.bwh.harvard.edu.
Background The creatine kinase (CK) reaction is important for rapid resynthesis of ATP when the heart increases its work. Studies defining the CK system in human failing and nonfailing myocardium are limited and in conflict. To resolve this conflict, we measured the activities of CK and its isoenzymes and the contents of creatine and CK-B in homogenates of human myocardium.
Methods and Results Myocardium was sampled from 23 subjects who underwent heart transplant, 36 subjects maintained in an intensive care unit before heart harvesting, 13 accident victims, and 2 patients undergoing heart surgery. Since the characteristics of myocardium of potential organ donors differed from those of myocardium of accident victims, data are presented for three groups: failing, donor, and control. CK activity was 7.7±1.9 and 6.0±1.4 IU/mg protein in left (LV) and right (RV) ventricles of failing, 9.4±2.5 and 10.7±2 IU/mg protein in LV and RV of donor, and 11.6±2.4 IU/mg protein in LV of control hearts. CK-MM and the mitochondrial isoenzyme activities were lower in failing and donor LV, and CK-MB activity and CK-B content were higher in failing and donor hearts. Creatine contents were 64±25 and 56±18.6 nmol/mg protein in LV and RV of failing, 96±30 and 110±24 nmol/mg protein in LV and RV of donor, and 131±28 nmol/mg protein in LV of control hearts.
Conclusions In failing and nonfailing donor human myocardium, there is a combined decrease of CK activity and creatine that may impair the ability to deliver ATP to energy-consuming systems.
Key Words: heart failure • cardiomyopathy • creatine kinase • creatine • transplantation
This article has been cited by other articles:
 |
|
 |
|
  T. T. Phan, G. N. Shivu, A. Choudhury, K. Abozguia, C. Davies, U. Naidoo, I. Ahmed, Z. Yousef, J. Horowitz, and M. Frenneaux Multi-centre experience on the use of perhexiline in chronic heart failure and refractory angina: old drug, new hope Eur J Heart Fail, September 1, 2009; 11(9): 881 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Michels, I. F. Khan, J. Endres-Becker, D. Rottlaender, S. Herzig, A. Ruhparwar, T. Wahlers, and U. C. Hoppe Regulation of the Human Cardiac Mitochondrial Ca2+ Uptake by 2 Different Voltage-Gated Ca2+ Channels Circulation, May 12, 2009; 119(18): 2435 - 2443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Ingwall Energy metabolism in heart failure and remodelling Cardiovasc Res, February 15, 2009; 81(3): 412 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Joubert, J. R. Wilding, D. Fortin, V. Domergue-Dupont, M. Novotova, R. Ventura-Clapier, and V. Veksler Local energetic regulation of sarcoplasmic and myosin ATPase is differently impaired in rats with heart failure J. Physiol., November 1, 2008; 586(21): 5181 - 5192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Eisen Exercise Training and Myocardial Energetics in Patients With Heart Failure: When More Is Less J. Am. Coll. Cardiol., May 13, 2008; 51(19): 1892 - 1895. [Full Text] [PDF]
|
|
|
|
 |
|
 I. Pinz, S. E. Ostroy, K. Hoyer, H. Osinska, J. Robbins, J. D. Molkentin, and J. S. Ingwall Calcineurin-induced energy wasting in a transgenic mouse model of heart failure Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1459 - H1466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. V. Zingman, A. E. Alekseev, D. M. Hodgson-Zingman, and A. Terzic ATP-sensitive potassium channels: metabolic sensing and cardioprotection J Appl Physiol, November 1, 2007; 103(5): 1888 - 1893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J. Kemi, M. A. Hoydal, P. M. Haram, A. Garnier, D. Fortin, R. Ventura-Clapier, and O. Ellingsen Exercise training restores aerobic capacity and energy transfer systems in heart failure treated with losartan Cardiovasc Res, October 1, 2007; 76(1): 91 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Neubauer The Failing Heart -- An Engine Out of Fuel N. Engl. J. Med., March 15, 2007; 356(11): 1140 - 1151. [Full Text] [PDF]
|
|
|
|
 |
|
 Y J. Woo, T. J Grand, G. P Liao, and C. M Panlilio Off-pump revascularization for significant left ventricular dysfunction. Asian Cardiovasc Thorac Ann, August 1, 2006; 14(4): 306 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Cullen, A. H.Y. Yuen, L. E. Felkin, R. T. Smolenski, J. L. Hall, S. Grindle, L. W. Miller, E. J. Birks, M. H. Yacoub, and P. J.R. Barton Myocardial Expression of the Arginine:Glycine Amidinotransferase Gene Is Elevated in Heart Failure and Normalized After Recovery: Potential Implications for Local Creatine Synthesis Circulation, July 4, 2006; 114(1_suppl): I-16 - I-20. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fragasso, G. Perseghin, F. De Cobelli, A. Esposito, A. Palloshi, G. Lattuada, P. Scifo, G. Calori, A. Del Maschio, and A. Margonato Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure Eur. Heart J., April 2, 2006; 27(8): 942 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Saks, P. Dzeja, U. Schlattner, M. Vendelin, A. Terzic, and T. Wallimann Cardiac system bioenergetics: metabolic basis of the Frank-Starling law J. Physiol., March 1, 2006; 571(2): 253 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wallis, C. A. Lygate, A. Fischer, M. ten Hove, J. E. Schneider, L. Sebag-Montefiore, D. Dawson, K. Hulbert, W. Zhang, M. H. Zhang, et al. Supranormal Myocardial Creatine and Phosphocreatine Concentrations Lead to Cardiac Hypertrophy and Heart Failure: Insights From Creatine Transporter-Overexpressing Transgenic Mice Circulation, November 15, 2005; 112(20): 3131 - 3139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Woo, T. J. Grand, M. F. Berry, P. Atluri, M. A. Moise, V. M. Hsu, J. Cohen, O. Fisher, J. Burdick, M. Taylor, et al. Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy J. Thorac. Cardiovasc. Surg., August 1, 2005; 130(2): 321 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. ten Hove, C. A. Lygate, A. Fischer, J. E. Schneider, A. E. Sang, K. Hulbert, L. Sebag-Montefiore, H. Watkins, K. Clarke, D. Isbrandt, et al. Reduced Inotropic Reserve and Increased Susceptibility to Cardiac Ischemia/Reperfusion Injury in Phosphocreatine-Deficient Guanidinoacetate-N-Methyltransferase-Knockout Mice Circulation, May 17, 2005; 111(19): 2477 - 2485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Weiss, G. Gerstenblith, and P. A. Bottomley ATP flux through creatine kinase in the normal, stressed, and failing human heart PNAS, January 18, 2005; 102(3): 808 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Ingwall and R. G. Weiss Is the Failing Heart Energy Starved?: On Using Chemical Energy to Support Cardiac Function Circ. Res., July 23, 2004; 95(2): 135 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ventura-Clapier, A. Garnier, and V. Veksler Energy metabolism in heart failure J. Physiol., February 15, 2004; 555(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Nakae, K. Mitsunami, T. Omura, T. Yabe, T. Tsutamoto, S. Matsuo, M. Takahashi, S. Morikawa, T. Inubushi, Y. Nakamura, et al. Proton magnetic resonance spectroscopy can detect creatine depletion associated with the progression of heart failure in cardiomyopathy J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1587 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Ogut and F. V. Brozovich Creatine Phosphate Consumption and the Actomyosin Crossbridge Cycle in Cardiac Muscles Circ. Res., July 11, 2003; 93(1): 54 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Harrison, M. H. van Wijhe, B. de Groot, F. J. Dijk, L. A. Gustafson, and J. H. G. M. van Beek Glycolytic buffering affects cardiac bioenergetic signaling and contractile reserve similar to creatine kinase Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H883 - H890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wendt, U. Schlattner, and T. Wallimann Differential Effects of Peroxynitrite on Human Mitochondrial Creatine Kinase Isoenzymes. INACTIVATION, OCTAMER DESTABILIZATION, AND IDENTIFICATION OF INVOLVED RESIDUES J. Biol. Chem., January 3, 2003; 278(2): 1125 - 1130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Beer, T. Seyfarth, J.o. Sandstede, W. Landschutz, C. Lipke, H. Kostler, M. von Kienlin, K. Harre, D. Hahn, and S. Neubauer Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with 31P-SLOOP magnetic resonance spectroscopy J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1267 - 1274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ventura-Clapier, E. De Sousa, and V. Veksler Metabolic Myopathy in Heart Failure Physiology, October 1, 2002; 17(5): 191 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. van der Laarse Hypothesis: troponin degradation is one of the factors responsible for deterioration of left ventricular function in heart failure Cardiovasc Res, October 1, 2002; 56(1): 8 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Spindler, R. Niebler, H. Remkes, M. Horn, T. Lanz, and S. Neubauer Mitochondrial creatine kinase is critically necessary for normal myocardial high-energy phosphate metabolism Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H680 - H687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Park, J. Zhang, Y. Ye, S. Ormaza, P. Liang, A. J. Bank, L. W. Miller, and R. J. Bache Myocardial creatine kinase expression after left ventricular assist device support J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1773 - 1779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Joubert, J.-L. Mazet, P. Mateo, and J. A. Hoerter 31P NMR Detection of Subcellular Creatine Kinase Fluxes in the Perfused Rat Heart. CONTRACTILITY MODIFIES ENERGY TRANSFER PATHWAYS J. Biol. Chem., May 17, 2002; 277(21): 18469 - 18476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Welsh, G. D. Kukes, and L. M. Sandweiss Differences of Creatine Kinase MB and Cardiac Troponin I Concentrations in Normal and Diseased Human Myocardium Ann. Clin. Lab. Sci., January 1, 2002; 32(1): 44 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Mettauer, J. Zoll, H. Sanchez, E. Lampert, F. Ribera, V. Veksler, X. Bigard, P. Mateo, E. Epailly, J. Lonsdorfer, et al. Oxidative capacity of skeletal muscle in heart failure patients versus sedentary or active control subjects J. Am. Coll. Cardiol., October 1, 2001; 38(4): 947 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-L. L. Boumans, J. H.C. Diris, M. Nap, A. M.M. Muijtjens, J. G. Maessen, M. P. van Dieijen-Visser, and W. T. Hermens Creatine Kinase Isoenzyme MB (CKMB) Controversy: Perimortal Tissue Acidosis May Explain the Absence of CKMB in Myocardium at Autopsy Clin. Chem., September 1, 2001; 47(9): 1733 - 1735. [Full Text] [PDF]
|
|
|
|
|
|
M. J. Mihm, F. Yu, C. A. Carnes, P. J. Reiser, P. M. McCarthy, D. R. Van Wagoner, and J. A. Bauer Impaired Myofibrillar Energetics and Oxidative Injury During Human Atrial Fibrillation Circulation, July 10, 2001; 104(2): 174 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Tian and E. D. Abel Responses of GLUT4-Deficient Hearts to Ischemia Underscore the Importance of Glycolysis Circulation, June 19, 2001; 103(24): 2961 - 2966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ye, G. Gong, K. Ochiai, J. Liu, and J. Zhang High-Energy Phosphate Metabolism and Creatine Kinase in Failing Hearts : A New Porcine Model Circulation, March 20, 2001; 103(11): 1570 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Mihm, C. M. Coyle, B. L. Schanbacher, D. M. Weinstein, and J. A. Bauer Peroxynitrite induced nitration and inactivation of myofibrillar creatine kinase in experimental heart failure Cardiovasc Res, March 1, 2001; 49(4): 798 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Crilley, E. A. Boehm, B. Rajagopalan, A. M. Blamire, P. Styles, F. Muntoni, D. Hilton-Jones, and K. Clarke Magnetic resonance spectroscopy evidence of abnormal cardiac energetics in Xp21 muscular dystrophy J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1953 - 1958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. P. Chacko, F. Aresta, S. M. Chacko, and R. G. Weiss MRI/MRS assessment of in vivo murine cardiac metabolism, morphology, and function at physiological heart rates Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2218 - H2224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. De Sousa, V. Veksler, X. Bigard, P. Mateo, and R. Ventura-Clapier Heart Failure Affects Mitochondrial but Not Myofibrillar Intrinsic Properties of Skeletal Muscle Circulation, October 10, 2000; 102(15): 1847 - 1853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Lorell and B. A. Carabello Left Ventricular Hypertrophy : Pathogenesis, Detection, and Prognosis Circulation, July 25, 2000; 102(4): 470 - 479. [Full Text] [PDF]
|
|
|
|
|
|
X.-H. Ning, J. Zhang, J. Liu, Y. Ye, S.-H. Chen, A. H. L. From, R. J. Bache, and M. A. Portman Signaling and expression for mitochondrial membrane proteins during left ventricular remodeling and contractile failure after myocardial infarction J. Am. Coll. Cardiol., July 1, 2000; 36(1): 282 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wyss and R. Kaddurah-Daouk Creatine and Creatinine Metabolism Physiol Rev, July 1, 2000; 80(3): 1107 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Prabhu and G. L. Freeman Altered LV inotropic reserve and mechanoenergetics early in the development of heart failure Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H698 - H705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Miyamoto, F. del Monte, U. Schmidt, T. S. DiSalvo, Z. B. Kang, T. Matsui, J. L. Guerrero, J. K. Gwathmey, A. Rosenzweig, and R. J. Hajjar Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure PNAS, January 18, 2000; 97(2): 793 - 798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hugel, M. Horn, M. de Groot, H. Remkes, C. Dienesch, K. Hu, G. Ertl, and S. Neubauer Effects of ACE inhibition and beta -receptor blockade on energy metabolism in rats postmyocardial infarction Am J Physiol Heart Circ Physiol, December 1, 1999; 277(6): H2167 - H2175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Neubauer, H. Remkes, M. Spindler, M. Horn, F. Wiesmann, J. Prestle, B. Walzel, G. Ertl, G. Hasenfuss, and T. Wallimann Downregulation of the Na+-Creatine Cotransporter in Failing Human Myocardium and in Experimental Heart Failure Circulation, November 2, 1999; 100(18): 1847 - 1850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J.M. de Groot, K.W. H. Wodzig, M. L. Simoons, J. F.C. Glatz, and W. Th. Hermens Measurement of myocardial infarct size from plasma fatty acid-binding protein or myoglobin, using individually estimated clearance rates Cardiovasc Res, November 1, 1999; 44(2): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. De Sousa, V. Veksler, A. Minajeva, A. Kaasik, P. Mateo, E. Mayoux, J. Hoerter, X. Bigard, B. Serrurier, and R. Ventura-Clapier Subcellular Creatine Kinase Alterations : Implications in Heart Failure Circ. Res., July 9, 1999; 85(1): 68 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Horn, H. Remkes, C. Dienesch, K. Hu, G. Ertl, and S. Neubauer Chronic high-dose creatine feeding does not attenuate left ventricular remodeling in rat hearts post-myocardial infarction Cardiovasc Res, July 1, 1999; 43(1): 117 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. Dzeja, K. T. Vitkevicius, M. M. Redfield, J. C. Burnett, and A. Terzic Adenylate Kinase–Catalyzed Phosphotransfer in the Myocardium : Increased Contribution in Heart Failure Circ. Res., May 28, 1999; 84(10): 1137 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Harrison, M. H. van Wijhe, B. de Groot, F. J. Dijk, and J. H. G. M. van Beek CK inhibition accelerates transcytosolic energy signaling during rapid workload steps in isolated rabbit hearts Am J Physiol Heart Circ Physiol, January 1, 1999; 276(1): H134 - H140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kameyama, Z. Chen, S. P. Bell, P. VanBuren, D. Maughan, and M. M. LeWinter Mechanoenergetic Alterations During the Transition From Cardiac Hypertrophy to Failure in Dahl Salt-Sensitive Rats Circulation, December 22, 1998; 98(25): 2919 - 2929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Saupe, M. Spindler, R. Tian, and J. S. Ingwall Impaired Cardiac Energetics in Mice Lacking Muscle-Specific Isoenzymes of Creatine Kinase Circ. Res., May 4, 1998; 82(8): 898 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Neubauer, M. Horn, M. Cramer, K. Harre, J. B. Newell, W. Peters, T. Pabst, G. Ertl, D. Hahn, J. S. Ingwall, et al. Myocardial Phosphocreatine-to-ATP Ratio Is a Predictor of Mortality in Patients With Dilated Cardiomyopathy Circulation, October 7, 1997; 96(7): 2190 - 2196. [Abstract] [Full Text]
|
|
|
|
|
|
R. Tian, L. Nascimben, J. S. Ingwall, and B. H. Lorell Failure to Maintain a Low ADP Concentration Impairs Diastolic Function in Hypertrophied Rat Hearts Circulation, August 19, 1997; 96(4): 1313 - 1319. [Abstract] [Full Text]
|
|
|
|
|
|
K. W. Saupe, M. Spindler, J. C. A. Hopkins, W. Shen, and J. S. Ingwall Kinetic, Thermodynamic, and Developmental Consequences of Deleting Creatine Kinase Isoenzymes from the Heart. REACTION KINETICS OF THE CREATINE KINASE ISOENZYMES IN THE INTACT HEART J. Biol. Chem., June 23, 2000; 275(26): 19742 - 19746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Pucar, E. Janssen, P. P. Dzeja, N. Juranic, S. Macura, B. Wieringa, and A. Terzic Compromised Energetics in the Adenylate Kinase AK1 Gene Knockout Heart under Metabolic Stress J. Biol. Chem., December 22, 2000; 275(52): 41424 - 41429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Pucar, P. P. Dzeja, P. Bast, N. Juranic, S. Macura, and A. Terzic Cellular Energetics in the Preconditioned State. PROTECTIVE ROLE FOR PHOSPHOTRANSFER REACTIONS CAPTURED BY 18O-ASSISTED 31P NMR J. Biol. Chem., November 21, 2001; 276(48): 44812 - 44819. [Abstract] [Full Text] [PDF]
|
|