This Article Full Text 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 Lopaschuk, G. D. Articles by Stanley, W. C. Search for Related Content PubMed PubMed Citation Articles by Lopaschuk, G. D. Articles by Stanley, W. C.

(Circulation. 1997;95:313-315.)
© 1997 American Heart Association, Inc.

Articles

Glucose Metabolism in the Ischemic Heart

Gary D. Lopaschuk, PhD; William C. Stanley, PhD

the Cardiovascular Disease Research Group (G.D.L.), Faculty of Medicine, The University of Alberta, Edmonton, Alberta, Canada, and Department of Physiology and Biophysics (W.C.S.), School of Medicine, Case Western Reserve University, Cleveland, Ohio.

Key Words: Editorials • glucose • fatty acids • myocardial infarction • GLUT 1 • GLUT 4

	Introduction

 
A number of clinical trials are presently evaluating whether stimulating glucose metabolism is an effective therapeutic approach to lessening the severity of ischemic injury (see References 1, 2, and 3 for reviews). Several pharmacological agents with demonstrated anti-ischemic effects have also recently been shown to act by stimulating glucose metabolism (ie, ranolazine, trimetazidine, L-carnitine, and propionyl L-carnitine).^{3 4} Despite these encouraging results, the regulation of glucose metabolism during ischemia remains poorly understood. Although many experimental studies have addressed the changes in cellular metabolism that occur during and subsequent to ischemia,^{3 5} little is known about the effects of ischemia on the actual transport of glucose into the heart. It has long been known that myocardial ischemia results in an increase in the rate of glycolysis and a switch from lactate uptake by the heart to lactate production.⁵ The glucose for glycolysis originates from both the breakdown of myocardial glycogen stores and the uptake of glucose from the blood (Figure). The rate of glucose uptake by the heart during ischemia is dependent on the severity of the reduction in blood flow.⁶ It is increased with less severe ischemia but decreases with severe ischemia when glucose delivery to the tissue is very low. In any case, ischemia consistently causes a large increase in the extraction of glucose from the blood, reflecting a greater capacity for glucose transport across the sarcolemmal membrane.⁶

View larger version (29K): [in this window] [in a new window]   Figure 1. Overview of carbohydrate and fatty acid metabolism in the heart. PFK indicates phosphofructokinase; GAPDH, glyceraldehyde-phosphate dehydrogenase; and PDH, . . . [Full Text of this Article]

This article has been cited by other articles:

				H. S. Thatte, L. Rousou, B. E. Hussaini, X.-G. Lu, P. R. Treanor, and S. F. Khuri Development and Evaluation of a Novel Solution, Somah, for the Procurement and Preservation of Beating and Nonbeating Donor Hearts for Transplantation Circulation, October 27, 2009; 120(17): 1704 - 1713. [Abstract] [Full Text] [PDF]

				S. K. Banerjee, K. R. McGaffin, N. M. Pastor-Soler, and F. Ahmad SGLT1 is a novel cardiac glucose transporter that is perturbed in disease states Cardiovasc Res, October 1, 2009; 84(1): 111 - 118. [Abstract] [Full Text] [PDF]

				M. A. Schroeder, H. J. Atherton, D. R. Ball, M. A. Cole, L. C. Heather, J. L. Griffin, K. Clarke, G. K. Radda, and D. J. Tyler Real-time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy FASEB J, August 1, 2009; 23(8): 2529 - 2538. [Abstract] [Full Text] [PDF]

				H. Tuunanen, E. Engblom, A. Naum, K. Nagren, M. Scheinin, B. Hesse, K.E. Juhani Airaksinen, P. Nuutila, P. Iozzo, H. Ukkonen, et al. Trimetazidine, a Metabolic Modulator, Has Cardiac and Extracardiac Benefits in Idiopathic Dilated Cardiomyopathy Circulation, September 16, 2008; 118(12): 1250 - 1258. [Abstract] [Full Text] [PDF]

				E. Inglese, L. Leva, R. Matheoud, G. Sacchetti, C. Secco, M. Brambilla, P. Gandolfo, and G. Sambuceti Reply: High Intraindividual Variability of Global Myocardial 18F-FDG Uptake over Time J. Nucl. Med., September 1, 2008; 49(9): 1570 - 1571. [Full Text] [PDF]

				V. W. Dolinsky and J. R. B. Dyck Role of AMP-activated protein kinase in healthy and diseased hearts Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2557 - H2569. [Abstract] [Full Text] [PDF]

				G. Fragasso, A. Palloshi, P. Puccetti, C. Silipigni, A. Rossodivita, M. Pala, G. Calori, O. Alfieri, and A. Margonato A Randomized Clinical Trial of Trimetazidine, a Partial Free Fatty Acid Oxidation Inhibitor, in Patients With Heart Failure J. Am. Coll. Cardiol., September 5, 2006; 48(5): 992 - 998. [Abstract] [Full Text] [PDF]

				S. J. Crozier, T. C. Vary, S. R. Kimball, and L. S. Jefferson Cellular energy status modulates translational control mechanisms in ischemic-reperfused rat hearts Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1242 - H1250. [Abstract] [Full Text] [PDF]

				M. Keith and L. Errett Myocardial Metabolism and Improved OutcomesAfter High Risk Heart Surgery Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2005; 9(2): 167 - 171. [Abstract] [PDF]

				Y. Xu, M. Gen, L. Lu, J. Fox, S. O. Weiss, R. D. Brown, D. Perlov, H. Ahmad, P. Zhu, C. Greyson, et al. PPAR-{gamma} activation fails to provide myocardial protection in ischemia and reperfusion in pigs Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1314 - H1323. [Abstract] [Full Text] [PDF]

				M. Suleiman, H. Hammerman, M. Boulos, M. R. Kapeliovich, A. Suleiman, Y. Agmon, W. Markiewicz, and D. Aronson Fasting Glucose Is an Important Independent Risk Factor for 30-Day Mortality in Patients With Acute Myocardial Infarction: A Prospective Study Circulation, February 15, 2005; 111(6): 754 - 760. [Abstract] [Full Text] [PDF]

				S. G. Lloyd, P. Wang, H. Zeng, and J. C. Chatham Impact of low-flow ischemia on substrate oxidation and glycolysis in the isolated perfused rat heart Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H351 - H362. [Abstract] [Full Text] [PDF]

				P. Wang and J. C. Chatham Onset of diabetes in Zucker diabetic fatty (ZDF) rats leads to improved recovery of function after ischemia in the isolated perfused heart Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E725 - E736. [Abstract] [Full Text] [PDF]

				M. P. Chandler, P. N. Chavez, T. A. McElfresh, H. Huang, C. S. Harmon, and W. C. Stanley Partial inhibition of fatty acid oxidation increases regional contractile power and efficiency during demand-induced ischemia Cardiovasc Res, July 1, 2003; 59(1): 143 - 151. [Abstract] [Full Text] [PDF]

				R. Southworth and P. B. Garlick Dobutamine responsiveness, PET mismatch, and lack of necrosis in low-flow ischemia: is this hibernation in the isolated rat heart? Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H316 - H324. [Abstract] [Full Text] [PDF]

				Y. Xu, L. Lu, C. Greyson, J. Lee, M. Gen, K. Kinugawa, C. S. Long, and G. G. Schwartz Deleterious Effects of Acute Treatment With a Peroxisome Proliferator-Activated Receptor-{gamma} Activator in Myocardial Ischemia and Reperfusion in Pigs Diabetes, May 1, 2003; 52(5): 1187 - 1194. [Abstract] [Full Text] [PDF]

				G. D. Lopaschuk, I. M. Rebeyka, and M. F. Allard Metabolic Modulation: A Means to Mend a Broken Heart Circulation, January 15, 2002; 105(2): 140 - 142. [Full Text] [PDF]

				S.L. Chierchia Trimetazidine and left ventricular ischaemic dysfunction: an overview of clinical evidence Eur. Heart J. Suppl., November 1, 2001; 3(suppl_O): O16 - O20. [Abstract] [PDF]

				R. Moudgil, Y. Xu, V. Menon, and B. I. Jugdutt Effect of Chronic AT1 Receptor Antagonism on Postischemic Functional Recovery and AT1/AT2 Receptor Proteins in Isolated Working Rat Hearts Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2001; 6(2): 183 - 188. [Abstract] [PDF]

				L. M. King, R. J. Sidell, J. R. Wilding, G. K. Radda, and K. Clarke Free fatty acids, but not ketone bodies, protect diabetic rat hearts during low-flow ischemia Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1173 - H1181. [Abstract] [Full Text] [PDF]

				P. Zhu, L. Lu, Y. Xu, and G. G. Schwartz Troglitazone Improves Recovery of Left Ventricular Function After Regional Ischemia in Pigs Circulation, March 14, 2000; 101(10): 1165 - 1171. [Abstract] [Full Text] [PDF]

				P. Zhu, L. Lu, Y. Xu, C. Greyson, and G. G. Schwartz Glucose-insulin-potassium preserves systolic and diastolic function in ischemia and reperfusion in pigs Am J Physiol Heart Circ Physiol, February 1, 2000; 278(2): H595 - H603. [Abstract] [Full Text] [PDF]

				W. R. Ford, A. S. Clanachan, and B. I. Jugdutt Characterization of Cardioprotection Mediated by AT2 Receptor Antagonism After Ischemia-Reperfusion in Isolated Working Rat Hearts Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(3): 211 - 221. [Abstract] [PDF]

				T. FUKUSE, T. HIRATA, T. NAKAMURA, M. KAWASHIMA, S. HITOMI, and H. WADA Influence of Deflated and Anaerobic Conditions During Cold Storage on Rat Lungs Am. J. Respir. Crit. Care Med., August 1, 1999; 160(2): 621 - 627. [Abstract] [Full Text]

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