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The effect of insulin on the heart

Part 2: Effects on function during and post myocardial ischaemia

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Abstract

Insulin infusion has been advocated in the treatment of myocardial ischaemia and myocardial infarction. There is evidence from experimental animal studies for a protective effect of high-dose insulin administration in myocardial ischaemia and myocardial infarction. In some relatively small study populations a reduction in mortality was reported in those patients who received glucose-insulin-potassium (GIK) during myocardial infarction, which was confirmed in two meta-analyses. However, it has not been possible to reproduce these positive results in large randomised clinical trials. (Neth Heart J 2010;18:255-9.)

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References

  1. Jonassen AK, Sack MN, Mjos OD, Yellon DM. Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling. Circ Res. 2001;89:1191-8.

    Google Scholar 

  2. Weissler AM, Altschuld RA, Gibb LE, Pollack ME, Kruger FA. Effect of insulin on the performance and metabolism of the anoxic isolated perfused rat heart. Circ Res. 1973 January;32:108-16.

    Google Scholar 

  3. Doenst T, Richwine RT, Bray MS, Goodwin GW, Frazier OH, Taegtmeyer H. Insulin improves functional and metabolic recovery of reperfused working rat heart. Ann Thorac Surg. 1999;67:1682-8.

    Google Scholar 

  4. Angelos MG, Murray HN, Gorsline RT, Klawitter PF. Glucose, insulin and potassium (GIK) during reperfusion mediates improved myocardial bioenergetics. Resuscitation. 2002;55:329-36.

    Google Scholar 

  5. Henry PD, Sobel BE, Braunwald E. Protection of hypoxic guinea pig hearts with glucose and insulin. Am J Physiol. 1974;226:309-13.

    Google Scholar 

  6. Apstein CS, Gravino FN, Haudenschild CC. Determinants of a protective effect of glucose and insulin on the ischemic myocardium. Effects on contractile function, diastolic compliance, metabolism, and ultrastructure during ischemia and reperfusion. Circ Res. 1983;52:515-26.

    Google Scholar 

  7. 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;68:466-81.

    Google Scholar 

  8. Vanoverschelde JL, Janier MF, Bakke JE, Marshall DR, Bergmann SR. Rate of glycolysis during ischemia determines extent of ischemic injury and functional recovery after reperfusion. Am J Physiol. 1994;267:H1785-H1794.

    Google Scholar 

  9. Krause BL, Wakefield JS, McMillan AB, Brown AH. Protection of the ischaemic myocardium by glucose-insulin-potassium infusion assessed by ventricular function and electron microscopy. J Cardiovasc Surg (Torino). 1978;19:421-32.

    Google Scholar 

  10. Ahmed SS, Lee CH, Oldewurtel HA, Regan TJ. Sustained effect of glucose-insulin-potassium on myocardial performance during regional ischemia. Role of free fatty acid and osmolality. J Clin Invest. 1978;61:1123-35.

    Google Scholar 

  11. Heng MK, Norris RM, Peter T, Nisbet HD, Singh BN. The effect of glucose-insulin-potassium on experimental myocardial infarction in the dog. Cardiovasc Res. 1978;12:429-35.

    Google Scholar 

  12. Tune JD, Mallet RT, Downey HF. Insulin improves contractile function during moderate ischemia in canine left ventricle. Am J Physiol. 1998;274:H1574-H1581.

    Google Scholar 

  13. Tune JD, Mallet RT, Downey HF. Insulin improves cardiac contractile function and oxygen utilization efficiency during moderate ischemia without compromising myocardial energetics. J Mol Cell Cardiol. 1998;30:2025-35.

    Google Scholar 

  14. Zhu P, Lu L, Xu Y, Greyson C, Schwartz GG. Glucose-insulin-potassium preserves systolic and diastolic function in ischemia and reperfusion in pigs. Am J Physiol. 2000;278:H595-H603.

    Google Scholar 

  15. Cave AC, Ingwall JS, Friedrich J, Liao R, Saupe KW, Apstein CS, et al. ATP synthesis during low-flow ischemia: influence of increased glycolytic substrate. Circulation. 2000;101:2090-6.

    Google Scholar 

  16. Szabo Z, Arnqvist H, Hakanson E, Jorfeldt L, Svedjeholm R. Effects of high-dose glucose-insulin-potassium on myocardial metabolism after coronary surgery in patients with Type II diabetes. Clin Sci (Lond). 2001;101:37-43.

    Google Scholar 

  17. Lazar HL, Zhang X, Rivers S, Bernard S, Shemin RJ. Limiting ischemic myocardial damage using glucose-insulin-potassium solutions. Ann Thorac Surg. 1995;60:411-6.

    Google Scholar 

  18. Jonassen AK, Aasum E, Riemersma RA, Mjos OD, Larsen TS. Glucose-insulin-potassium reduces infarct size when administered during reperfusion. Cardiovasc Drugs Ther. 2000;14:615-23.

    Google Scholar 

  19. Maroko PR, Libby P, Sobel BE, Bloor CM, Sybers HD, Shell WE et al. Effect of glucose-insulin-potassium infusion on myocardial infarction following experimental coronary artery occlusion. Circulation. 1972;45:1160-75.

    Google Scholar 

  20. Bellows SD, Kloner RA. Glucose-Insulin-Potassium does not reduce myocardial infarct size in an ischemic/reperfusion rabbit model. J Thromb Thrombolysis. 1998;5:25-7.

    Google Scholar 

  21. Haneda T, Ganz W, Burnam MH, Katz J. Metabolic effects of glucose-insulin-potassium in the ischemic myocardium. Jpn Heart J. 1978;19:376-82.

    Google Scholar 

  22. Calva E, Mújica A, Núñez R, Aoki K, Bisteni A, Sodi-Pallares D. Mitochondrial biochemical changes and glucose-KCl-insulin solution in cardiac infarct. Am J Physiol. 1966;211:71-6.

    Google Scholar 

  23. Kambara H, Yoshida A, Kawashita K, Kawai C. Effects of glucose-insulin-potassium infusion on myocardial infarction and myocardial blood flow following experimental coronary artery occlusion. Jpn Circ J. 1981;45:1158-63.

    Google Scholar 

  24. Dalby AJ, Bricknell OL, Opie LH. Effect of glucose-insulin-potassium infusions on epicardial ECG changes and on myocardial metabolic changes after coronary artery ligation in dogs. Cardiovasc Res 1981;15:588-98.

    Google Scholar 

  25. Sybers HD, Maroko PR, Ashraf M, Libby P, Braunwald E. The effect of glucose-insulin-potassium on cardiac ultrastructure following acute experimental coronary occlusion. Am J Pathol. 1973;70:401-20.

    Google Scholar 

  26. Zhang HF, Fan Q, Qian XX, Lopez BL, Christopher TA, Ma XL, et al. Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion. Apoptosis 2004;9:777-83.

    Google Scholar 

  27. 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 

  28. Sodi-Pallares D, Testilli MR, Fishleder BL, Bisteni A, Medrano GA, Friedland C et al. Effects of an intravenous infusion of a potassium-glucose-insulin solution on the electrocardiographic signs of myocardial infarction. A preliminary report. Am J Cardiol. 1962;5:166-81.

    Google Scholar 

  29. Sievers J, Lindh J, Johansson BW, Karnell J. Acute myocardial infarction treated by glucose-insulin-potassium (GIK) infusion. Cardiology. 1966;49:239-47.

    Google Scholar 

  30. Mittra B. Potassium, glucose, and insulin in treatment of myocardial infarction. Lancet. 1965;286:607-9.

    Google Scholar 

  31. Pilcher J, Etismahudin M, Exon P, Moore J. Potassium, glucose, and insulin in myocardial infarction [letter]. Lancet. 1967;289:1109.

    Google Scholar 

  32. Medical Research Council working-party on the treatment of myocardial infarction. Potassium, glucose, and insulin treatment for acute myocardial infarction. Lancet. 1968;292:1355-60.

    Google Scholar 

  33. Pentecost BL, Mayne NM, Lamb P. Controlled trial of intravenous glucose, potassium, and insulin in acute myocardial infarction. Lancet. 1968;291:946-8.

    Google Scholar 

  34. Rogers WJ, Stanley AW, Jr., Breinig JB, Prather JW, McDaniel HG, Moraski RE, et al. Reduction of hospital mortality rate of acute myocardial infarction with glucose-insulin-potassium infusion. Am Heart J. 1976;92:441-54.

    Google Scholar 

  35. Heng MK, Norris RM, Singh BN, Barratt-Boyes C. Effects of glucose and glucose-insulin-potassium on haemodynamics and enzyme release after acute myocardial infarction. Br Heart J. 1977;39:748-57.

    Google Scholar 

  36. Rogers WJ, Segall PH, McDaniel HG, Mantle JA, Russell RO, Jr., Rackley CE. Prospective randomized trial of glucose-insulin-potassium in acute myocardial infarction. Effects on myocardial hemodynamics, substrates and rhythm. Am J Cardiol. 1979;43:801-9.

    Google Scholar 

  37. Satler LF, Green CE, Kent KM, Pallas RS, Pearle DL, Rackley CE. Metabolic support during coronary reperfusion. Am Heart J 1987;114:54-8.

    Google Scholar 

  38. Fath-Ordoubadi F, Beatt KJ. Glucose-insulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials. Circulation. 1997;96:1152-6.

    Google Scholar 

  39. Malmberg K, Ryden L, Efendic S, Herlitz J, Nicol P, Waldenstrom A, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol. 1995;26:57-65.

    Google Scholar 

  40. Malmberg K, Norhammar A, Wedel H, Ryden L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin- Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study. Circulation. 1999;99:2626-32.

    Google Scholar 

  41. Malmberg K, Ryden L, Wedel H, Birkeland K, Bootsma A, Dickstein K, et al. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J. 2005;26:650-61.

    Google Scholar 

  42. Cheung NW, Wong VW, McLean M. The Hyperglycemia: Intensive Insulin Infusion in Infarction (HI-5) study: a randomized controlled trial of insulin infusion therapy for myocardial infarction. Diabetes Care. 2006;29:765-70.

    Google Scholar 

  43. Pache J, Kastrati A, Mehilli J, Bollwein H, Ndrepepa G, Schuhlen H, et al. A randomized evaluation of the effects of glucose-insulin-potassium infusion on myocardial salvage in patients with acute myocardial infarction treated with reperfusion therapy. Am Heart J. 2004;148:e3.

    Google Scholar 

  44. Diaz R, Paolasso EA, Piegas LS, Tajer CD, Moreno MG, Corvalan R, et al. Metabolic modulation of acute myocardial infarction. The ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group. Circulation. 1998;98:2227-34.

    Google Scholar 

  45. Ceremuzynski L, Budaj A, Czepiel A, Burzykowski T, Achremczyk P, Smielak-Korombel W, et al. Low-dose glucose-insulin-potassium is ineffective in acute myocardial infarction: results of a randomized multicenter Pol-GIK trial. Cardiovasc Drugs Ther. 1999;13:191-200.

    Google Scholar 

  46. van der Horst IC, Zijlstra F, van 't Hof AW, Doggen CJ, de Boer MJ, Suryapranata H, et al. Glucose-insulin-potassium infusion inpatients treated with primary angioplasty for acute myocardial infarction: the glucose-insulin-potassium study: a randomized trial. J Am Coll Cardiol. 2003;42:784-91.

    Google Scholar 

  47. Rasoul S, Ottervanger JP, Timmer JR, Svilaas T, Henriques JP, Dambrink JH, et al. One year outcomes after glucose-insulin-potassium in ST elevation myocardial infarction. The Glucose-insulin-potassium study II. Int J Cardiol. 2007;122:52-5.

    Google Scholar 

  48. Mehta SR, Yusuf S, Diaz R, Zhu J, Pais P, Xavier D, et al. Effect of glucose-insulin-potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: the CREATE-ECLA randomized controlled trial. JAMA. 2005;293:437-46.

    Google Scholar 

  49. Diaz R, Goyal A, Mehta SR, Afzal R, Xavier D, Pais P et al. Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction. JAMA. 2007;28;298:2399-405.

    Google Scholar 

  50. Klein LJ, Visser FC. The effect of insulin on the Heart. Part 1: Effects on metabolism and function. Neth Heart J 2010;18:255-0.

    Google Scholar 

  51. Cheung NW, Wong VW, McLean M. Insulin infusion therapy for myocardial infarction. Expert Opin Pharmacother. 2006;7:2495-503.

    Google Scholar 

  52. Diaz-Araya G, Nettle D, Castro P, Miranda F, Greig D, Campos X, et al. Oxidative stress after reperfusion with primary coronary angioplasty: lack of effect of glucose-insulin-potassium infusion. Crit Care Med. 2002;30:417-21.

    Google Scholar 

  53. Castro PF, Larrain G, Baeza R, Corbalan R, Nazzal C, Greig DP, et al. Effects of glucose-insulin-potassium solution on myocardial salvage and left ventricular function after primary angioplasty. Crit Care Med. 2003;31:2152-5.

    Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, VU Medical Centre, PO Box 7057, 1007, MB, Amsterdam, the Netherlands

    L. J. Klein

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    L. J. Klein

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Department of Cardiology, VU Medical Centre, Amsterdam, the Netherlands

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Klein, L.J., Visser, F.C. The effect of insulin on the heart. NHJL 18, 255–259 (2010). https://doi.org/10.1007/BF03091772

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