Effect of Glucose-Insulin-Potassium infusion on systolic and diastolic functions in patients with chronic ischemic cardiomyopathy

Document Type : Original Article


1 Saman Heart Clinic, Mashhad, Iran

2 Cardiology department, Mehr Hospital, Mashhad, Iran

3 Chemical and Biomolecular Department ,UCLA,USA



Background:Ischemic cardiomyopathy is accompanied with some degrees of decreased metabolism.So,a method to facilitate cellular absorption and use of glucose may promote myocardial function and viability .Glucose,Potassium.Insulin solution(GIK) has been used by some successful results in acute ischemic heart disease and decreases the extent of ischemic zone in myocardium and promote ventricular function.
Method and Materials: 25 patients with ischemic cardiomyopathy(EF<40%)with stable clinical condition who referred to emergency department or clinic of cardiology were enrolled in our study.They were assessed by echocardiographic indexes before and after GIK administration to evaluate the effects of GIK on systolic and diastolic function of the heart in chronic ischemic cardiomyopathy.
Results: Male to female ratio was 4:1 in our study. According to echocardiographic findings, left heart end diastolic indexes didn't show any significant statistical changes (p>0.005) but diastolic function of left ventricle were improved significantly after administration of GIK (p <0.005) .Despite there wasn't outstanding change on improvement of systolic left and right ventricular function (p>0.005), but because of metabolic improvements and increased in ventricular function after GIK administration, clinical symptoms were decreased.
Conclusion:GIK solution administration(As an accessible and cost-effective agent) may improve ventricular diastolic function and clinical symptoms,so we suggest GIK as an effective therapeutic method in ischemic cardiomyopathy.


1.Alderman EL, Fisher LD, Litwin P, Kaiser GC, Myers WO, Maynard C, Levine F, Schloss M. Results of coronary artery surgery in patients with poor left ventricular function (CASS). Circulation. 1983 Oct;68(4):785-95. doi: 10.1161/01.cir.68.4.785.
2.Bolli R. Myocardial 'stunning' in man. Circulation. 1992 Dec;86(6):1671-91. doi: 10.1161/01.cir.86.6.1671.
3.Rahimtoola SH. The hibernating myocardium. Am Heart J. 1989 Jan;117(1):211-21. doi: 10.1016/0002-8703(89)90685-6.
4.Diamond GA, Forrester JS, deLuz PL, Wyatt HL, Swan HJ. Post-extrasystolic potentiation of ischemic myocardium by atrial stimulation. Am Heart J. 1978 Feb;95(2):204-9. doi: 10.1016/0002-8703(78)90464-7.
5. Vanoverschelde JL, Melin JA. The pathophysiology of myocardial hibernation: current controversies and future directions. Prog Cardiovasc Dis. 2001 Mar-Apr;43(5):387-98. doi: 10.1053/pcad.2001.20655.
6.Lazar HL. Enhanced preservation of acutely ischemic myocardium and improved clinical outcomes using glucose-insulin-potassium (GIK) solutions. Am J Cardiol. 1997 Aug 4;80(3A):90A-93A. doi: 10.1016/s0002-9149(97)00462-1.
7.Cottin y , Lhuilier I,GILSON L,ZellerM,Bonnet c, Toulouse c, et al Glucose insulin potassium infusion improves systolic function in patients with chronic ischemic cardiomyopathy.eur J Heart Fail 2002؛ 4(2):181-4.dio.org/10.1016/S1388-9842(01)00222-7
8.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 Aug;39(2):381-92. doi: 10.1016/s0008-6363(98)00100-x.
9.Opie LH, Owen P. Effect of glucose-insulin-potassium infusions on arteriovenous differences of glucose of free fatty acids and on tissue metabolic changes in dogs with developing myocardial infarction. Am J Cardiol. 1976 Sep;38(3):310-21. doi: 10.1016/0002-9149(76)90173-9. PMID: 961606.
10.Lazar HL, Philippides G, Fitzgerald C, Lancaster D, Shemin RJ, Apstein C. Glucose-insulin-potassium solutions enhance recovery after urgent coronary artery bypass grafting. J Thorac Cardiovasc Surg. 1997 Feb;113(2):354-60; discussion 360-2. doi: 10.1016/S0022-5223(97)70333-7.
11.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 May;61(5):1123-35. doi: 10.1172/JCI109027.
12.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 Jul;52(1):49-57. doi: 10.1161/01.cir.52.1.49.
13. Stefano Di Marco; Beatrice Boldrini; Umberto Conti; Gabriella Marcucci; Cecilia Morgantini; Ele Ferrannini; Andrea Natali.Effects of GIK (glucose–insulin–potassium) on stress-induced myocardial ischaemia. Clin Sci (Lond) (2010) 119 (1): 37–44.doi:10.1042/CS20090438.
14.Lu C, Dabrowski P, Fragasso G, Chierchia SL. Effects of trimetazidine on ischemic left ventricular dysfunction in patients with coronary artery disease. Am J Cardiol. 1998 Oct 1;82(7):898-901. doi: 10.1016/s0002-9149(98)00500-1.
15.Brottier L, Barat JL, Combe C, Boussens B, Bonnet J, Bricaud H. Therapeutic value of a cardioprotective agent in patients with severe ischaemic cardiomyopathy. Eur Heart J. 1990 Mar;11(3):207-12. doi: 10.1093/oxfordjournals.eurheartj.a059685.
16.Seely EW.The ischemic heart disease.In:Brounwald,Zipes,Libby heart disease.6th ed.Philadelphia:W B Saunders;2001.P.2151-2174
17.EberliFR,Weinberg EO , Grice WN ,et al.protektive effect of increased glycolytic substrate against systolic and diastolic dysfunction and increased coronary resistance from prolonged underperfusion and reperfusion in isololated rabbit hearts perfused with erythrocyte suspensions.circ Res1991؛ 68(2):466.81.doi:10.1161/01.res.68.2.466.
18.ChinER,Allen OG. Effects of reduced muscle glycogen concentration on ffroce ca2+ release and contractile protein function in intact mouse skeletal muscle.Jphysiol(long)1997؛ 498(pt1):17-29.doi:10.1113/jphysiol.1997.sp021838
19. R Carbo,E Rodiguez.A glucose-insulin-potassium improves glucose intake in hypoxic cardiomyocytes  by a differential expression of glucose transporter in a metabolic syndrome model.J Biosci 2019;44:19,1-8.doi:10.1007/s12038-018-9833-7.
20.Linda Mellbin & Lars Rydén (2012) Evidence for a beneficial effect of glucose–insulin–potassium in patients with acute coronary syndromes. Did the IMMEDIATE trial solve an unanswered question?, Expert Review of Cardiovascular Therapy, 2014;10:9, 1097-1099
21.Alan S,Ulgen MS , Dedeoglu I ,kaya H,Toprak N .Long-term glucose insulin potassium infusion improves systolic and diastolic function in patients with chronic ischemic cardiomyopathy.sw med wkly .2003 jul26؛  133(29-30):419-22.
22.Khoury VK, Haluska B, Prins J, Marwick TH. Effects of glucose-insulin-potassium infusion on chronic ischaemic left ventricular dysfunction. Heart. 2003 Jan;89(1):61-5. doi: 10.1136/heart.89.1.61.
23.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 Heart Circ Physiol. 2000 Feb;278(2):H595-603. doi: 10.1152/ajpheart.2000.278.2.H595.
24.Marano l .bestetti a ,lomuscio a ,Tagliabue l, castini d ,tarricone d, Dario p, tarolo HL , fiorentini c. effects of infusion of glucose-insulin-potassium on myocardial function after a recent myocardial infarction.acta cardiol.2000feb,55(1)9-15
25.Ramanathan T, Morita S, Huang Y, Shirota K, Nishimura T, Zheng X, Hunyor SN. Glucose-insulin-potassium solution improves left ventricular energetics in chronic ovine diabetes. Ann Thorac Surg. 2004 Apr;77(4):1408-14. doi: 10.1016/j.athoracsur.2003.10.016.
26.Harry P. Selker,Joni R. Beshansky, Patricia R. Sheehan,et al. Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes: The IMMEDIATE Randomized Controlled Trial. JAMA. 2012; 307(18):1925-1933.doi: 10.1001/jama.2012.426. Epub 2012 Mar 27.
27- EifermanD,Perez-Tamayo RA,ABE K,OkumE,Higgins R. Real-Time monitoring of cardiac metabolism using biosensors show myocardial protection during ischemia-reperfusion ingury with glucose-insulin-potassiumadministration.Surgery.2007Aug:142(2):150-5.dio:10.1016/j.surg.2007.03.005.
28-Ramanathan T, Shirota K, Morita S, Nishimura T, Huang Y, Hunyor SN. Glucose-insulin-potassium solution improves left ventricular mechanics in diabetes. Ann Thorac Surg. 2002 Feb;73(2):582-7. doi: 10.1016/s0003-4975(01)03324-0.
29. Straus S, Gerc V, Kacila M, Faruk C. Glucosa-Insulin-Potassium (GIK) solution used with diabetic patients provides better recovery after coronary bypass operations. Med Arch. 2013;67(2):84-7.
30. Suhail Ahmad,1 Rana Altaf Ahmad,2 Bilal Ahsan Qureshi,3 and Mirza Ahmad Raza Baig.Myocardial protection with Glucose-Insulin-Potassium infusion during adult cardiac surgery. Pak J Med Sci. 2017 Mar-Apr; 33(2): 325–329.doi:10.12669/pjms.332.12414
31.Kun Zhao, Yue Zhang, Jia Li, Qin Cui,Rong Zhao,Wensheng Chen, Jincheng Liu, Bijun Zhao, Yi Wan, Xin-Liang Ma,Shiqiang Yu,Dinghua Yi, and Feng Gao.Modified Glucose Insulin Potassium Regimen Provides Cardioprotection With Improved Tissue Perfusion in Patients Undergoing Cardiopulmonary Bypass Surgery. J Am Heart Assoc. 2020;9.doi:10.1161/JAHA.119.012376.
32.Malmberg K,Ryden L,Efendic S,et al.Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acut myocardial infarction(DIGAMI study):Effects on mortality at 1 year.J Am Cardiol 1995(3);26-37.doi:10.1016/0735-1097(95)00126-k.
33.Díaz R, Paolasso EA, Piegas LS, Tajer CD, Moreno MG, Corvalán R, Isea JE, Romero G. Metabolic modulation of acute myocardial infarction. The ECLA (Estudios Cardiológicos Latinoamérica) Collaborative Group. Circulation. 1998 Nov 24;98(21):2227-34. doi: 10.1161/01.
34.Haider W, Eckersberger F, Wolner E. Preventive insulin administration for myocardial protection in cardiac surgery. Anesthesiology. 1984 May;60(5):422-9. doi: 10.1097/00000542-198405000-00006.
35.Cardillo C, Nambi SS, Kilcoyne CM, Choucair WK, Katz A, Quon MJ, Panza JA. Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation. 1999 Aug 24;100(8):820-5. doi: 10.1161/01.cir.100.8.820.
36.Ulgen MS, Alan S, Akdemir O, Toprak N. The effect of glucose-insulin-potassium solution on ventricular late potentials and heart rate variability in acute myocardial infarction. Coron Artery Dis. 2001 Sep;12(6):507-12. doi: 10.1097/00019501-200109000-00010.
37.Whitlow PL, Rogers WJ, Smith LR, McDaniel HG, Papapietro SE, Mantle JA, Logic JR, Russell RO Jr, Rackley CE. Enhancement of left ventricular function by glucose-insulin-potassium infusion in acute myocardial infarction. Am J Cardiol. 1982 Mar;49(4):811-20. doi: 10.1016/0002-9149(82)91963-4.
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 Aug 19;96(4):1152-6. doi: 10.1161/01.cir.96.4.1152.