(Circulation. 1998;98:2227-2234.)
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports |
Metabolic Modulation of Acute Myocardial Infarction
The ECLA Glucose-Insulin-Potassium Pilot Trial
From the Department of Cardiology, Instituto Cardiovascular de Rosario, Rosario, Argentina (R.D., E.A.P., G.R.); Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brasil (L.S.P.); Critical Care Unit, Sanatorio de la Providencia, Buenos Aires, Argentina (C.D.T.); Catheterization Laboratory, Instituto Nacional de Cardiología `Ignacio Chavez,' México DF, México (M.G.M.); Department of Cardiovascular Diseases, Hospital Clínico, Universidad Católica de Chile, Santiago, Chile (R.C.); and the Critical Care Unit, Hospital Dr Domingo Luciani, Caracas, Venezuela (J.E.I.).
Correspondence to Rafael Diaz, MD, ECLA Estudios Cardiológicos Latinoamérica, Bv Oroño 500. 2000 Rosario, Argentina. E-mail ecla{at}satlink.com
Background—Several trials have been performed in the past using glucose, insulin, and potassium infusion (GIK) for the treatment of acute myocardial infarction (AMI). Because of continuing uncertainty about the potential role of this therapeutic intervention, we conducted a randomized trial to evaluate the impact of a GIK solution during the first hours of AMI.
Methods and Results—Four hundred seven patients with suspected AMI admitted within 24 hours of symptoms onset were enrolled. In a ratio of 2:1, 268 patients were allocated to receive GIK (high- or low-dose) and 139 to receive control. Phlebitis and serum changes in the plasma concentration of glucose or potassium were observed more often with GIK. A trend toward a nonsignificant reduction in major and minor in-hospital events was observed in patients allocated to GIK. In 252 patients (61.9%) treated with reperfusion strategies, a statistically significant reduction in mortality (relative risk [RR] 0.34; 95% CI: 0.15 to 0.78; 2P=0.008) and a consistent trend toward fewer in-hospital events in the GIK group were observed.
Conclusions—Our results confirm that a metabolic modulation strategy in the first hours of an AMI is feasible, applicable worldwide, and has mild side effects. The statistically significant mortality reduction in patients who underwent a reperfusion strategy might have important implications for the management of AMI patients. It is now essential to perform a large-scale trial to reliably determine the magnitude of benefit.
Key Words: myocardial infarction • ischemia • glucose • insulin • potassium • coronary disease
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A. P. Furnary, G. Gao, G. L. Grunkemeier, Y. Wu, K. J. Zerr, S. O. Bookin, H. S. Floten, and A. Starr Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., May 1, 2003; 125(5): 1007 - 1021. [Abstract] [Full Text] [PDF]
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D. Tanne and Y. Schwammenthal Editorial Comment--Hyperglycemia and Early Reperfusion Therapy Stroke, May 1, 2003; 34(5): 1240 - 1241. [Full Text] [PDF]
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M. N. Sack and D. M. Yellon Insulin therapy as an adjunct toreperfusion after acute coronary ischemia: A proposed direct myocardial cell survival effect independent of metabolic modulation J. Am. Coll. Cardiol., April 16, 2003; 41(8): 1404 - 1407. [Abstract] [Full Text] [PDF]
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C.-H. Wang, N. Leung, N. Lapointe, L. Szeto, K. D. Uffelman, A. Giacca, J. L. Rouleau, and G. F. Lewis Vasopeptidase Inhibitor Omapatrilat Induces Profound Insulin Sensitization and Increases Myocardial Glucose Uptake in Zucker Fatty Rats: Studies Comparing a Vasopeptidase Inhibitor, Angiotensin-Converting Enzyme Inhibitor, and Angiotensin II Type I Receptor Blocker Circulation, April 15, 2003; 107(14): 1923 - 1929. [Abstract] [Full Text] [PDF]
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J. G. Bovill Anesthesia for Patients with Impaired Ventricular Function Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2003; 7(1): 49 - 54. [PDF]
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H. B. van Wezel and S. W. M. d. Jong Clinical Use of Glucose-Insulin-Potassium in Cardiac Surgery andAcute Myocardial Infarction: An Overview Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2003; 7(1): 77 - 83. [PDF]
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T. Doenst, W. Bothe, and F. Beyersdorf Therapy with insulin in cardiac surgery: controversies and possible solutions Ann. Thorac. Surg., February 1, 2003; 75(2): S721 - 728. [Abstract] [Full Text] [PDF]
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P. Dandona, A. Aljada, and A. Bandyopadhyay The Potential Therapeutic Role of Insulin in Acute Myocardial Infarction in Patients Admitted to Intensive Care and in Those With Unspecified Hyperglycemia Diabetes Care, February 1, 2003; 26(2): 516 - 519. [Full Text] [PDF]
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J. Sundell and J. Knuuti Insulin and myocardial blood flow Cardiovasc Res, February 1, 2003; 57(2): 312 - 319. [Abstract] [Full Text] [PDF]
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J. Yang, A. K. Gillingham, A. Hodel, F. Koumanov, B. Woodward, and G. D. Holman Insulin-stimulated cytosol alkalinization facilitates optimal activation of glucose transport in cardiomyocytes Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1299 - E1307. [Abstract] [Full Text] [PDF]
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R. K. Kudej, L. T. White, A. B. Kudej, S. F. Vatner, and E. D. Lewandowski Brief Increase in Carbohydrate Oxidation After Reperfusion Reverses Myocardial Stunning in Conscious Pigs Circulation, November 26, 2002; 106(22): 2836 - 2841. [Abstract] [Full Text] [PDF]
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N. N. Wahab, E. A. Cowden, N. J. Pearce, M. J. Gardner, H. Merry, J. L. Cox, and ICONS Investigators Is blood glucose an independent predictor of mortality in acute myocardial infarction in the thrombolytic era? J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1748 - 1754. [Abstract] [Full Text] [PDF]
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L. Ryden and K. Malmberg Who are the enemies? Diabetes mellitus -- a major risk factor for ischaemic myocardial injury: new directions in the management of acute coronary syndromes in the diabetic patient Eur. Heart J. Suppl., November 1, 2002; 4(suppl_G): G21 - G25. [Abstract] [PDF]
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 J Sala, R Masia, F-J Gonzalez de Molina, J M Fernandez-Real, M Gil, D Bosch, W Ricart, M Senti, and J Marrugat Short-term mortality of myocardial infarction patients with diabetes or hyperglycaemia during admission J Epidemiol Community Health, September 1, 2002; 56(9): 707 - 712. [Abstract] [Full Text] [PDF]
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 A. Takahashi, Y. Kureishi, J. Yang, Z. Luo, K. Guo, D. Mukhopadhyay, Y. Ivashchenko, D. Branellec, and K. Walsh Myogenic Akt Signaling Regulates Blood Vessel Recruitment during Myofiber Growth Mol. Cell. Biol., July 1, 2002; 22(13): 4803 - 4814. [Abstract] [Full Text] [PDF]
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H. L. Lazar The Insulin Cardioplegia Trial J. Thorac. Cardiovasc. Surg., May 1, 2002; 123(5): 842 - 844. [Full Text] [PDF]
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W. A. Lell, V. G. Nielsen, D. C. McGiffin, F. E. Schmidt Jr, J. K. Kirklin, and A. W. Stanley Jr Glucose-insulin-potassium infusion for myocardial protection during off-pump coronary artery surgery Ann. Thorac. Surg., April 1, 2002; 73(4): 1246 - 1251. [Abstract] [Full Text] [PDF]
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J. Sundell, P. Nuutila, H. Laine, M. Luotolahti, K. Kalliokoski, O. Raitakari, and J. Knuuti Dose-Dependent Vasodilating Effects of Insulin on Adenosine-Stimulated Myocardial Blood Flow Diabetes, April 1, 2002; 51(4): 1125 - 1130. [Abstract] [Full Text] [PDF]
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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]
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T. Ramanathan, K. Shirota, S. Morita, T. Nishimura, Y. Huang, and S. N. Hunyor Glucose-insulin-potassium solution improves left ventricular mechanics in diabetes Ann. Thorac. Surg., February 1, 2002; 73(2): 582 - 587. [Abstract] [Full Text] [PDF]
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H.-P. Hermann, O. Zeitz, S. E Lehnart, B. Keweloh, N. Datz, G. Hasenfuss, and P. M.L Janssen Potentiation of beta-adrenergic inotropic response by pyruvate in failing human myocardium Cardiovasc Res, January 1, 2002; 53(1): 116 - 123. [Abstract] [Full Text] [PDF]
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 M. F. Oliver Prevention of Ventricular Fibrillation During Acute Myocardial Ischemia: Control of Free Fatty Acids Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2001; 6(3): 213 - 217. [Abstract] [PDF]
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R. Ramasamy, Y. Hwang, S. Bakr, and S. R. Bergmann Protection of ischemic hearts perfused with an anion exchange inhibitor, DIDS, is associated with beneficial changes in substrate metabolism Cardiovasc Res, August 1, 2001; 51(2): 275 - 282. [Abstract] [Full Text] [PDF]
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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]
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G.D. Lopaschuk Trimetazidine in AMI Eur. Heart J., June 1, 2001; 22(11): 977 - 978. [PDF]
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C J BROOMHEAD and M P COLVIN Glucose, insulin, and the cardiovascular system Heart, May 1, 2001; 85(5): 495 - 496. [Full Text]
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