Circulation Research, Vol 70, 1180-1190, Copyright © 1992 by American Heart Association

ARTICLES

Relation between glycolysis and calcium homeostasis in postischemic myocardium

RW Jeremy, Y Koretsune, E Marban and LC Becker
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Md.

This study examined the hypothesis that glycolysis is required for functional recovery of the myocardium during reperfusion by facilitating restoration of calcium homeostasis. [Ca2+]i was measured in isolated perfused rabbit hearts by using the Ca2+ indicator 1,2- bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F- BAPTA) and 19F nuclear magnetic resonance spectroscopy. In nonischemic control hearts, inhibition of glycolysis with iodoacetate did not alter [Ca2+]i. In hearts subjected to 20 minutes of global zero-flow ischemia, [Ca2+]i increased from 260 +/- 80 nM before ischemia to 556 +/- 44 nM after 15 minutes of ischemia (p less than 0.05). After reperfusion with 5 mM pyruvate as a carbon substrate, [Ca2+]i increased further in hearts with intact glycolysis to 851 +/- 134 nM (p less than 0.05 versus ischemia) during the first 10 minutes of reperfusion, before returning to preischemic levels. In contrast, inhibition of glycolysis during the reperfusion period resulted in persistent severe calcium overload ([Ca2+]i, 1,380 +/- 260 nM after 15 minutes of reperfusion, p less than 0.02 versus intact glycolysis group). Furthermore, despite the presence of pyruvate and oxygen, inhibition of glycolysis during early reperfusion resulted in greater impairment of functional recovery (rate/pressure product, 3,722 +/- 738 mm Hg/min) than did reperfusion with pyruvate and intact glycolysis (rate/pressure product, 9,851 +/- 590 mm Hg/min, p less than 0.01). Inhibition of glycolysis during early reperfusion was also associated with a marked increase in left ventricular end-diastolic pressure during reperfusion (41 +/- 5 mm Hg) compared with hearts with intact glycolysis (16 +/- 2 mm Hg, p less than 0.01). The detrimental effects of glycolytic inhibition during early reperfusion were, however, prevented by initial reperfusion with a low calcium solution ([Ca]o, 0.63 mM for 30 minutes, then 2.50 mM for 30 minutes). In these hearts, the rate/pressure product after 60 minutes of reperfusion was 12,492 +/- 1,561 mm Hg/min (p less than 0.01 versus initial reflow with [Ca]o of 2.50 mM). These findings indicate that the functional impairment observed in postischemic myocardium is related to cellular Ca2+ overload. Glycolysis appears to play an important role in restoration of Ca2+ homeostasis and recovery of function of postischemic myocardium.

This article has been cited by other articles:

				L. Zhou, H. Huang, T. A. McElfresh, D. A. Prosdocimo, and W. C. Stanley Impact of anaerobic glycolysis and oxidative substrate selection on contractile function and mechanical efficiency during moderate severity ischemia Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H939 - H945. [Abstract] [Full Text] [PDF]

				C. Montessuit, I. Papageorgiou, and R. Lerch Nuclear Receptor Agonists Improve Insulin Responsiveness in Cultured Cardiomyocytes through Enhanced Signaling and Preserved Cytoskeletal Architecture Endocrinology, March 1, 2008; 149(3): 1064 - 1074. [Abstract] [Full Text] [PDF]

				F. Chen, C. De Diego, L.-H. Xie, J.-H. Yang, T. S Klitzner, and J. N Weiss Effects of metabolic inhibition on conduction, Ca transients, and arrhythmia vulnerability in embryonic mouse hearts Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2472 - H2478. [Abstract] [Full Text] [PDF]

				R. Barillas, I. Friehs, H. Cao-Danh, J. F. Martinez, and P. J. del Nido Inhibition of Glycogen Synthase Kinase-3{beta} Improves Tolerance to Ischemia in Hypertrophied Hearts Ann. Thorac. Surg., July 1, 2007; 84(1): 126 - 133. [Abstract] [Full Text] [PDF]

				A. V. Zima, J. Kockskamper, and L. A. Blatter Cytosolic energy reserves determine the effect of glycolytic sugar phosphates on sarcoplasmic reticulum Ca2+ release in cat ventricular myocytes J. Physiol., November 15, 2006; 577(1): 281 - 293. [Abstract] [Full Text] [PDF]

				J. N. Weiss, L. Yang, and Z. Qu Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Network perspectives of cardiovascular metabolism J. Lipid Res., November 1, 2006; 47(11): 2355 - 2366. [Abstract] [Full Text] [PDF]

				W. C. Stanley, F. A. Recchia, and G. D. Lopaschuk Myocardial Substrate Metabolism in the Normal and Failing Heart Physiol Rev, July 1, 2005; 85(3): 1093 - 1129. [Abstract] [Full Text] [PDF]

				C. S. Apstein The benefits of glucose-insulin-potassium for acute myocardial infarction (and some concerns) J. Am. Coll. Cardiol., September 3, 2003; 42(5): 792 - 795. [Full Text] [PDF]

				C. E Huggins, A. A Domenighetti, T. Pedrazzini, S. Pepe, and L. M. Delbridge Elevated intracardiac angiotensin II leads to cardiac hypertrophy and mechanical dysfunction in normotensive mice Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 186 - 190. [Abstract] [PDF]

				I. Friehs, H. Cao-Danh, C. Stamm, D. B. Cowan, F. X. McGowan, and P. J. del Nido Postnatal increase in insulin-sensitive glucose transporter expression is associated with improved recovery of postischemic myocardial function J. Thorac. Cardiovasc. Surg., July 1, 2003; 126(1): 263 - 271. [Abstract] [Full Text] [PDF]

				O. J Sichelschmidt, C. Hahnefeld, T. Hohlfeld, F. W Herberg, and K. Schror Trapidil protects ischemic hearts from reperfusion injury by stimulating PKAII activity Cardiovasc Res, June 1, 2003; 58(3): 602 - 610. [Abstract] [Full Text] [PDF]

				M. E. Jessen Glucose control during cardiac surgery: How sweet it is J. Thorac. Cardiovasc. Surg., May 1, 2003; 125(5): 985 - 987. [Full Text] [PDF]

				C.J. Zuurbier Postischemic Myocardial Metabolism Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2003; 7(1): 59 - 65. [PDF]

				S. Bruemmer-Smith, M. S. Avidan, B. Harris, S. Sudan, R. Sherwood, J. B. Desai, F. Sutherland, and J. Ponte Glucose, insulin and potassium for heart protection during cardiac surgery Br. J. Anaesth., April 1, 2002; 88(4): 489 - 495. [Abstract] [Full Text] [PDF]

				Q. Liu, J. C. Docherty, J. C. T. Rendell, A. S. Clanachan, and G. D. Lopaschuk High levels of fatty acids delay the recoveryof intracellular pH and cardiac efficiency inpost-ischemic hearts by inhibiting glucose oxidation J. Am. Coll. Cardiol., February 20, 2002; 39(4): 718 - 725. [Abstract] [Full Text] [PDF]

				E. O. McFalls, B. Murad, J.-S. Liow, M. C. Gannon, H. C. Haspel, A. Lange, D. Marx, J. Sikora, and H. B. Ward Glucose uptake and glycogen levels are increased in pig heart after repetitive ischemia Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H205 - H211. [Abstract] [Full Text] [PDF]

				I. Friehs, C. Stamm, H. Cao-Danh, F. X. McGowan Jr, and P. J. del Nido Insulin-like growth factor-1 improves postischemic recovery in hypertrophied hearts Ann. Thorac. Surg., November 1, 2001; 72(5): 1650 - 1656. [Abstract] [Full Text] [PDF]

				L. D. Monti, S. Allibardi, P. M. Piatti, G. Valsecchi, S. Costa, G. Pozza, S. Chierchia, and M. Samaja Triglycerides impair postischemic recovery in isolated hearts: roles of endothelin-1 and trimetazidine Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1122 - H1130. [Abstract] [Full Text] [PDF]

				J. N. Weiss and P. Korge The Cytoplasm: No Longer a Well-Mixed Bag Circ. Res., July 20, 2001; 89(2): 108 - 110. [Full Text] [PDF]

				J. G. Van Emous, C. L. A. M. Vleggeert-Lankamp, M. G. J. Nederhoff, T. J. C. Ruigrok, and C. J. A. Van Echteld Postischemic Na+-K+-ATPase reactivation is delayed in the absence of glycolytic ATP in isolated rat hearts Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2189 - H2195. [Abstract] [Full Text] [PDF]

				F. Weekers, E. Van Herck, J. Isgaard, and G. Van den Berghe Pretreatment with Growth Hormone-Releasing Peptide-2 Directly Protects against the Diastolic Dysfunction of Myocardial Stunning in an Isolated, Blood-Perfused Rabbit Heart Model Endocrinology, November 1, 2000; 141(11): 3993 - 3999. [Abstract] [Full Text] [PDF]

				R. T. Mallet Pyruvate: Metabolic Protector of Cardiac Performance Experimental Biology and Medicine, February 1, 2000; 223(2): 136 - 148. [Abstract] [Full Text]

				C. Depre and H. Taegtmeyer Metabolic aspects of programmed cell survival and cell death in the heart Cardiovasc Res, February 1, 2000; 45(3): 538 - 548. [Abstract] [Full Text] [PDF]

				K. Imahashi, H. Kusuoka, K. Hashimoto, J. Yoshioka, H. Yamaguchi, and T. Nishimura Intracellular Sodium Accumulation During Ischemia as the Substrate for Reperfusion Injury Circ. Res., June 25, 1999; 84(12): 1401 - 1406. [Abstract] [Full Text] [PDF]

				C. Depre, J.-L. J. Vanoverschelde, and H. Taegtmeyer Glucose for the Heart Circulation, February 2, 1999; 99(4): 578 - 588. [Full Text] [PDF]

				C. S. Apstein Glucose-Insulin-Potassium for Acute Myocardial Infarction : Remarkable Results From a New Prospective, Randomized Trial Circulation, November 24, 1998; 98(21): 2223 - 2226. [Full Text] [PDF]

				K. Y. Xu and L. C. Becker Ultrastructural Localization of Glycolytic Enzymes on Sarcoplasmic Reticulum Vesicles J. Histochem. Cytochem., April 1, 1998; 46(4): 419 - 428. [Abstract] [Full Text]

				J. Dizon, D. Burkhoff, J. Tauskela, J. Whang, P. Cannon, and J. Katz Metabolic inhibition in the perfused rat heart: evidence for glycolytic requirement for normal sodium homeostasis Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1082 - H1089. [Abstract] [Full Text] [PDF]

				S. A. Gabel, H. R. Cross, R. E. London, C. Steenbergen, and E. Murphy Decreased intracellular pH is not due to increased H+ extrusion in preconditioned rat hearts Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2257 - H2262. [Abstract] [Full Text] [PDF]

				M. M. Pike, C. S. Luo, S. Yanagida, G. R. Hageman, and P. G. Anderson 23Na and 31P Nuclear Magnetic Resonance Studies of Ischemia-Induced Ventricular Fibrillation : Alterations of Intracellular Na+ and Cellular Energy Circ. Res., August 1, 1995; 77(2): 394 - 406. [Abstract] [Full Text]

				K. Y. Xu, J. L. Zweier, and L. C. Becker Functional Coupling Between Glycolysis and Sarcoplasmic Reticulum Ca2+ Transport Circ. Res., July 1, 1995; 77(1): 88 - 97. [Abstract] [Full Text]

				W. D. Gao, D. Atar, P. H. Backx, and E. Marban Relationship Between Intracellular Calcium and Contractile Force in Stunned Myocardium : Direct Evidence for Decreased Myofilament Ca2+ Responsiveness and Altered Diastolic Function in Intact Ventricular Muscle Circ. Res., June 1, 1995; 76(6): 1036 - 1048. [Abstract] [Full Text]