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Glucose-Insulin-Potassium (GIK) for Acute Myocardial Infarction: A Negative Study with a Positive Value

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Abstract

Summary. Glucose-insulin-therapy for acute myocardial infarction (AMI) has had a long history, going back 37 years to the pioneering concepts of Sodi-Pallares. Although a recent meta-analysis of a number of smaller trials has suggested mortality benefit, it is only the South American trial, published in Circulation in 1998, that has been large enough to show a mortality benefit of GIK infusions when compared with controls in the same trial. In contrast, the Polish study published in this issue of this journal produced a negative result. The two chief differences between the studies are the much higher risk of mortality of the patients chosen for the positive trial, and the much higher dose of GIK that was used. Despite this positive trial information, and the very extensive experimental background (which is here reviewed), the present data are not firm nor extensive enough to support the routine use of GIK in patients with AMI. Thus more trials based on the concepts of metabolic therapy are required and are being organized. At present, a careful strategy of patient selection is advocated. In the case of diabetics with AMI, current evidence is already strong enough to recommend routine use of modified GIK for all such patients.

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References

  1. Diaz R, Paolasso EC, Piegas LS, et al. On behalf of the ECLA (Estudios Cardiologicas Lantinoamerica) Collaborative Group. Metabolic modulation of acute myocardial infarction. The ECLA glucose-insulin-potassium pilot trial. Circulation 1998;98:2227–2234.

    Google Scholar 

  2. Fath-Ordoubadi F, Beatt KJ. Glucose-insulin-potassium therapy for treatment of acute myocardial infarction: An overview of randomized placebo-controlled trials. Circulation 1997;96:1074–1077.

    Google Scholar 

  3. Apstein CS, Taegtmeyer H. Glucose-insulin-potassium in acute myocardial infarction. The time has come for a large, prospective trial. Circulation 1997;96:1074–1077.

    Google Scholar 

  4. Sodi-Pallares D, Testelli M, Fishelder F. Effects of an intravenous infusion of a potassium-insulin-glucose solution on the electrocardiographic signs of myocardial infarction. Am J Cardiol 1962;9:166–181.

    Google Scholar 

  5. Opie LH. The glucose hypothesis: Relation to acute myocardial ischaemia. J Mol Cell Cardiol 1970;1:107–114.

    Google Scholar 

  6. Maroko PR, Libby P, Sobel BE, et al. Effect of glucose-insulin-potassium infusion on myocardial infarction following experimental coronary artery occlusion. Circulation 1972;45:1160–1175.

    Google Scholar 

  7. Rovetto MJ, Whitmer JT, Neely JR. Comparison of the effects of anoxia and whole heart ischemia on carbohydrate utilisation in isolated working rat hearts. Circ Res 1973;32:699–711.

    Google Scholar 

  8. Opie LH, Bruyneel K, Owen P. Effects of glucose, insulin and potassium infusion on tissue metabolic changes within first hour of myocardial infarction in the baboon. Circulation 1975;52:49–57.

    Google Scholar 

  9. Hearse DJ, Humphrey SM, Feuvray D, de Leiris J. A biochemical and ultrastructural study of the species variation in myocardial cell damage. J Mol Cell Cardiol 1976;8:759–778.

    Google Scholar 

  10. Oliver MF, Opie LH. Effects of glucose and fatty acids on myocardial ischaemia and arrhythmias. Lancet 1994;343:155–158.

    Google Scholar 

  11. Opie LH, Tansey MJ, Kenelly BM. Proposed metabolic vicious circle in patients with large myocardial infarcts and high plasma free fatty acid concentrations. Lancet 1977;2:890–892.

    Google Scholar 

  12. Apstein CS, Gravino FN, Haudenschild CC. Determinants of a protective effect of glucose and insulin on the ischaemic myocardium. Effects of contractile function, diastolic compliance, metabolism, and ultrastructure during ischaemia and reperfusion. Circ Res 1983;52:515–526.

    Google Scholar 

  13. Owen P, Dennis S, Opie LH. Glucose flux rate regulates onset of ischemic contracture in globally underperfused rat hearts. Circ Res 1990;66:344–354.

    Google Scholar 

  14. Eberli FR, Weinberg EO, Grice WN, Horowitz GL, Apstein CS. Protective effect of increased glycolytic substrate against systolic and diastolic dysfunction and increased coronary resistance from prolonged global underperfusion and reperfusion in isolated rabbit hearts perfused with erythrocyte suspensions. Circ Res 1991;68:466–481.

    Google Scholar 

  15. King LM, Opie LH. Glucose delivery is a major determinant of glucose utilisation in the ischemic myocardium with a residual coronary flow. Cardiovasc Res 1998;39:381–392.

    Google Scholar 

  16. Oldfield GS, Commerford PJ, Opie LH. Effects of preoperative glucose-insulin-potassium on myocardial glycogen levels and on complications of mitral valve replacement. J Thorac Cardiovasc Surg 1986;91:874–878.

    Google Scholar 

  17. Cross HR, Opie LH, Radda GK, Clarke K. Is a high glycogen content beneficial or detrimental to the ischemic rat heart? Circ Res 1996;78:482–491.

    Google Scholar 

  18. Milavetz JJ, Giebel DW, Christian TF, Schwarts RS, Holmes DR, Gibbons RJ. Time to therapy and salvage in myocardial infarction. J Am Coll Cardiol 1998;31:1246–1251.

    Google Scholar 

  19. Apstein CS. Glucose-insulin-potassium for acute myocardial infarction. Remarkable results from a new prospective, randomized trial [editorial]. Circulation 1998;98,2223–2228.

    Google Scholar 

  20. Cave A, Eberli FR, Ngoy S, Rose J, Ingwall JS, Apstein CS. Increased glycolytic substrate protects against ischemic diastolic dysfunction: 31P-NMR studies in the isolated blood perfused rat heart. Circulation 1993;88(Suppl. I):143.

    Google Scholar 

  21. Saupe KW, Eberli FR, Ingwall JS, Apstein CS. Energetic and functional responses of hibernating hearts to inotropic stimulation and increased glycolytic substrates (abstr). Circulation 1997;96:1–160.

    Google Scholar 

  22. Cross HR, Radda GK, Clarke K. The role of Na+/K+ ATPase activity during low flow ischemia in preventing myocardial injury: A 31P, 23Na and 87Rb NMR spectroscopic study. Magn Reson Med 1995;34:673–685.

    Google Scholar 

  23. Bricknell OL, Daries PS, Opie LH. A relationship between adenosine triphosphate, glycolysis and ischaemic contracture in the isolated rat heart. J Mol Cell Cardiol 1981;13:941–945.

    Google Scholar 

  24. Weiss JN, Lamp ST. Glycolysis preferentially inhibits ATP-sensitive K+ channels in isolated guinea pig cardiac myocytes. Science 1987;238:67–70.

    Google Scholar 

  25. Xu KY, Zweier JL, Becker LC. Functional coupling between glycolysis and sarcoplasmic reticulum Ca transport. Circ Res 1995;77:88–97.

    Google Scholar 

  26. Psaty BM, Heckbert SR, Koepsell TD, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 1995;274:620–625.

    Google Scholar 

  27. Kondo RP, Apstein CS, Eberli FR, Tillotson DL, Suter TM. Increased calcium loading and inotropy without greater cell death in hypoxic rat cardiomyocytes. Am J Physiol 1998;275 (Heart Circ. Physical. 44):H2272–H2282.

    Google Scholar 

  28. Caldwell JH, Revenaugh JR, Martin GV, Johnson PM, Rasey JS, Krohn KA. Comparison of fluorine-18-fluorodeoxyglucose and tritiated fluoromisonidazole uptake during low-flow ischemia. J Nucl Med 1995;36:1633–1638.

    Google Scholar 

  29. Christian TF, O'Connor MK, Schwartz RS, Shepherd FJ, Gibbons RJ, Ritman EL. Technetium-99m MIBI to assess coronary collateral flow during acute myocardial infarction in two closed chest animal models. J Nucl Med 1997;38:1840–1846.

    Google Scholar 

  30. Jonassen AK, Brar BK, Mjos OD, Sack MN, Latchmann DS, Yellon DM. The cardioprotective effect of insulin at reperfusion — a possible antiapoptotic mechanism. Circulation 1999, submitted.

  31. Stanley AW, Moraski RE, Russell RO, et al. Effects of glucose-insulin-potassium on myocardial substrate availability and utilisation in stable coronary artery disease. Studies on myocardial arbohydrates, lipid and oxygen arterial-coronary sinus differences in patients with coronary artery disease. Am J Cardiol 1975;36:929–937.

    Google Scholar 

  32. Antman EM, Seelig MS, Fleischmann K, Lau J, Kuntz K. Magnesium in acute myocardial infarction: Scientific, statistical and economic rationale for its use. Cardiovasc Drugs Ther 1996;10:297–301.

    Google Scholar 

  33. Malmberg K, Ryden L, Hamsten A, Herlitz J, Waldenstrom A, Wedel H. Effects of insulin treatment on cause-specific one-year mortality and morbidity in diabetic patients with acute myocardial infarction. DIGAMI study group. Diabetes Insulin-Glucose in Acute Myocardial Infarction. Eur Heart J 1996;17:1337–1344.

    Google Scholar 

  34. Cunningham MJ, Apstein CS, Weinberg EO, Vogel WM, Lorell BH. Influence of glucose and insulin on the exaggerated diastolic and systolic dysfunction of hypertrophied rat hearts during hypoxia. Circ Res 1990;66:406–415.

    Google Scholar 

  35. Kagaya Y, Weinberg EO, Ito N, Mochizuki T, Barry WH, Lorell BH. Glycolytic inhibition: Effects on diastolic relaxation and intracellular calcium handling in hypertrophied rat ventricular myocytes. J Clin Invest 1995;95:2766–2776.

    Google Scholar 

  36. Coleman GM, Graniac S, Tagtmeyer H, Sweeney M, Frazier OH. Efficacy of metabolic support with glucose-insulin-potassium for left ventricular pump failure after aortocoronary bypass surgery. Circulation 1989;80(Suppl. I):191–196.

    Google Scholar 

  37. Coven DL, Suter TM, Eberli FR, Apstein CS. Dobutamine and glucose-insulin-potassium (GIK) improve cardiac function and survival in a randomzied trial of cardiogenic shock. Circulation 1994;90:1–480.

    Google Scholar 

  38. Lazar HL, Philippides G, Fitzgerald C, Lancaster D, Shemin RJ, Apstein CS. Glucose-insulin-potassium solutions enhance recovery after urgent coronary artery bypass grafting. J Thorac Cardiovasc Surg 1997;113:354–352.

    Google Scholar 

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Authors and Affiliations

  1. Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Boston University School of Medicine and Cardiology Section, Boston Medical Center, Boston, Massachusetts, USA

    Carl S. Apstein

  2. Cape Heart Centre, University of Cape Town Medical School, Observatory, Cape Town, South Africa

    Lionel H. Opie

Authors
  1. Carl S. Apstein
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  2. Lionel H. Opie
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Apstein, C.S., Opie, L.H. Glucose-Insulin-Potassium (GIK) for Acute Myocardial Infarction: A Negative Study with a Positive Value. Cardiovasc Drugs Ther 13, 185–189 (1999). https://doi.org/10.1023/A:1007757407246

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