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Ann Thorac Surg 1995;60:411-416
© 1995 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Limiting Ischemic Myocardial Damage Using Glucose-Insulin-Potassium Solutions

Department of Cardiothoracic Surgery, The Boston University Hospital, Boston, Massachusetts

Accepted for publication April 7, 1995.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. This experimental study sought to determine whether the infusion of glucose-insulin-potassium (GIK) solutions to ischemic myocardium during revascularization would decrease myocardial damage.

Methods. In 40 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 30 minutes of cardioplegic arrest and 180 minutes of reperfusion. During the periods of coronary occlusion and reperfusion, 10 pigs received GIK (glucose = 300 g/L, insulin = 50 U/L, K⁺ = 80 mEq/L) through the jugular vein at 1 mL • kg^-1 • h^-1 (GIK-IV group); 10 pigs received GIK through the coronary sinus (GIK-CS group); 5 pigs received GIK through the jugular vein during reperfusion only (GIK-R group); 5 pigs received GIK through the jugular vein 2 hours prior to coronary occlusion and then during the periods of coronary occlusion and reperfusion (GIK-Pre group); and 10 pigs received no GIK (Unmodified group). Ischemic damage was assessed by wall motion scores using two-dimensional echocardiography, changes in myocardial tissue pH, and the area of necrosis in the area of risk.

Results. Hearts treated with GIK had significantly less tissue acidosis, higher wall motion scores, and the least tissue necrosis (14% +/- 2% GIK-Pre versus 12% +/- 2% GIK-CS versus 16% +/- 2% GIK-IV versus 25% +/- 2% GIK-R versus 73% +/- 4% Unmodified; all, p < 0.05 versus Unmodified).

Conclusions. We conclude that a glucose-insulin-potassium solution reduces ischemic myocardial damage during coronary revascularization.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The primary energy source of the nonischemic myocardium is free fatty acids [1]. However, glucose appears to be a more favorable energy source for the myocardium during periods of ischemia and subsequent reperfusion [2]. During periods of coronary ischemia, exogenous glucose can stimulate glycolytic pathways, which are important in maintaining cell viability [1]. Adenosine triphosphate derived from glycolysis plays an important role in membrane ion transport, which is crucial to the cellular integrity of myocytes, endothelium, and vascular smooth muscle cells [3]. This leads to a reduction in cellular edema, which may prevent the ``no-flow'' phenomenon that occurs during reperfusion. Glucose also acts to esterify intracellular free fatty acids, thus decreasing the supply of oxygen free radicals [4].

In 1965, Sodi-Pollaris and colleagues [5] used glucose-insulin-potassium (GIK) solutions to limit electrocardiographic changes in acutely infarcting myocardium. Early studies using GIK solutions in isolated hearts with regional ischemia were promising. Infusion of GIK decreased infarct size [6], increased adenosine triphosphate and creatine phosphate levels [7], and improved mechanical function [8]. However, under conditions of severe, prolonged ischemia without periods of reperfusion, GIK increased tissue lactate accumulation, resulting in poor ventricular function [9]. After the introduction of cardioplegia, the role of GIK in cardiac surgery diminished. However, in recent years, the emergence of new interventional technologies such as percutaneous transluminal coronary angioplasty and thrombolysis has resulted in groups of patients who require coronary artery bypass grafting for acute myocardial ischemia. Despite prompt and expeditious coronary surgical revascularization, mortality and morbidity are significantly increased in these patients [10, 11]. Our own clinical and experimental studies [10--14] suggest that interventions aimed at decreasing ischemic damage prior to cardioplegic arrest and reperfusion will result in the best recovery of myocardial function. In particular, we [12] and others [15, 16] have shown that substrate enhancement prior to cardioplegic arrest in acutely ischemic myocardium may limit myocardial necrosis.

As exogenous glucose appears to be a superior substrate during periods of myocardial ischemia, we were interested to see whether GIK could significantly limit myocardial necrosis after the revascularization of an acute coronary occlusion in an experimental model. We were specifically interested in determining (1) whether GIK would also limit myocardial stunning, (2) the optimal period (preischemia, ischemia, reperfusion) for GIK delivery, (3) whether GIK would be equally effective if given intravenously or perfused directly into the coronary sinus, and (4) whether GIK would significantly decrease the incidence of ventricular arrhythmias.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Preparation
Forty adult pigs (weight, 18 to 34 kg) were premedicated with intramuscular morphine sulfate (2 mg/kg), anesthetized with -chloralose (75 mg/kg), and placed on positive-pressure endotracheal ventilation. After a median sternotomy, catheters were placed into the aorta and the femoral vein for monitoring systemic pressure and administering fluids. The azygos vein was ligated. The animals were then heparinized (3 mg/kg), and the second and third diagonal coronary arteries were occluded for 90 minutes with snares placed just distal to the takeoff of the left anterior descending coronary artery. Intravenous lidocaine hydrochloride was administered for ventricular arrhythmias. Ventricular fibrillation was treated with electric defibrillation. No inotropic agents were used.

After 90 minutes of coronary occlusion, all animals were placed on total cardiopulmonary bypass (Sarns membrane oxygenator; Sarns Inc, Ann Arbor, MI) with a 20F cannula in the femoral artery and a 36F venous return catheter in the right atrium. A 24F catheter was inserted into the left atrium to infuse volume so that left ventricular end-diastolic pressure could be varied. Mean arterial blood pressure ranged from 65 to 75 mm Hg, and pump flow was maintained at 80 mL • kg^-1 • min^-1. The hematocrit averaged 28% +/- 3%, and pH was maintained at 7.40 +/- 0.03.

After the institution of cardiopulmonary bypass, all hearts underwent 30 minutes of ischemic arrest with multidose antegrade hypothermic (4°C) crystalloid potassium cardioplegia (K⁺ = 25 mEq/L, pH = 7.6) supplemented with systemic (34°C) and topical hypothermia. After the arrest period, the cross-clamp was removed, the coronary snares were released, and all hearts were reperfused on cardiopulmonary bypass at 37°C for 180 minutes.

Treatment Groups
During the course of the experimental preparation, hearts were treated with one of five different interventions (Fig 1).

View larger version (35K): [in this window] [in a new window]   Fig 1. . The five experimental protocols. (CS = coronary sinus; GIK = glucose-insulin-potassium; IV = intravenous; R = reperfusion.)

GIK-PRE GROUP.
In 5 pigs, an intravenous infusion of GIK (glucose = 300 g/L, insulin = 50 U/L, K⁺ = 80 mEq/L) was instituted through a catheter in the right internal jugular vein at 1 mL • kg^-1 • h^-1 for 2 hours prior to the period of coronary occlusion. It was continued at the same rate during the periods of coronary occlusion and reperfusion.

GIK-IV GROUP.
In 10 pigs, GIK was instituted during the entire periods of coronary occlusion and reperfusion through a catheter in the right internal jugular vein.

GIK-CS GROUP.
In 10 pigs, a triple-lumen balloon-tipped catheter (9F; DLP Inc, Grand Rapids, MI) was inserted into the proximal coronary sinus through a pursestring suture in the right atrium. The GIK was administered through the coronary sinus catheter at 1 mL • kg^-1 • h^-1 during the periods of coronary occlusion and reperfusion.

GIK-R GROUP.
In 5 pigs, GIK was administered through a right internal jugular catheter at 1 mL • kg^-1 • h^-1 only during the period of reperfusion.

Measurements and Statistical Analyses
Electrocardiographic leads were placed to measure heart rate and monitor ventricular arrhythmias. The left ventricular end-diastolic pressure was recorded with a piezoelectric microtip catheter pressure transducer (Millar Instruments Inc, Houston, TX) inserted through a stab wound in the left ventricular apex. Systemic body temperature was measured with a rectal temperature probe (Yellow Springs Instrument Co, Yellow Springs, CO). Serum glucose and potassium measurements were made every 30 minutes.

Myocardial tissue pH was measured with a tissue pH probe (Khuri tissue ischemia monitor; Vascular Technology, North Chelmsford, MA) inserted into the area of risk between the second and third diagonal vessels as previously described [17]. The pH was standardized to myocardial tissue temperature and expressed in absolute numbers and as the change in pH (pH) from preischemic values. The pH and pH were recorded on-line and then averaged for the various experimental groups.

Echocardiographic short-axis and long-axis sections were obtained with a hand-held 3.5-MHz ultrasound transducer (ATL, Tempe, AZ). Left ventricular end-diastolic volume was obtained by planimetry of a perpendicular long-axis length and a short-axis area, and wall motion changes were assessed using short-axis sections as previously described [12]. A numerical score was used to determine the degree of wall motion abnormalities: 4 = normal; 3 = mild hypokinesis; 2 = moderate hypokinesis; 1 = severe hypokinesis; 0 = akinesis; and -1 = dyskinesis. The left ventricular end-diastolic volume was planimetered so that wall motion scores could be studied at comparable preload conditions with a stable afterload (mean arterial pressure = 65 mm Hg) using the right heart bypass technique. The wall motion scores in the myocardium at risk were determined in a blinded fashion by an experienced echocardiographer (Dr Sheilah Bernard) and were averaged for the periods of coronary artery occlusion and reperfusion for each experimental group.

The areas of risk and necrosis were determined by histochemical staining techniques using triphenyl-tetrazoleum chloride (Sigma Chemical Co, St. Louis, MO) following the 3-hour reperfusion period as previously described [12].

Data are presented as the mean +/- the standard error of the mean. Statistical evaluation between the five experimental groups was performed using analysis of variance techniques. Differences in variables measured on a continuous scale within each group were assessed by a paired Student's t test. Data were considered significant at a p value of less than 0.05.

All animals received humane care in compliance with the ``Guide for the Care and Use of Laboratory Animals'' published by the National Institutes of Health (NIH publication 85-23, revised 1985).

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The incidence of ventricular arrhythmias during the 90-minute period of coronary occlusion prior to cardiopulmonary bypass is shown in Figure 2. In the 10 animals receiving no GIK (Unmodified group), 7 (70%) had development of either ventricular fibrillation or major runs of sustained ventricular tachycardia (>ten beats). Animals that received GIK only during reperfusion (GIK-R group) also had an increased incidence of ventricular arrhythmias (60%, 3/5). The incidence of ventricular arrhythmias in the two groups that did not receive GIK during this period was significantly (p < 0.05) higher than in the three groups (GIK-Pre, GIK-IV, GIK-CS) that did receive GIK.

View larger version (13K): [in this window] [in a new window]   Fig 2. . Incidence of ventricular arrhythmias. Hearts treated with glucose-insulin-potassium (GIK) during the period of coronary occlusion (GIK-Pre, GIK-IV, GIK-CS) had a significantly lower incidence of ventricular arrhythmias (CS = coronary sinus; IV = intravenous; R = reperfusion.)

View larger version (23K): [in this window] [in a new window]   Fig 3. . Effect of glucose-insulin-potassium (GIK) therapy on serum K+ levels. Hearts not receiving GIK (Unmodified, GIK-R) during the period of coronary occlusion had significantly higher serum K+ levels after 90 minutes of coronary occlusion. Serum K+ levels were equivalent in all groups after 180 minutes of reperfusion. (CS = coronary sinus; IV = intravenous; R = reperfusion.)

View larger version (24K): [in this window] [in a new window]   Fig 4. . Effect of glucose-insulin-potassium (GIK) therapy on serum glucose levels. All hearts had similar glucose levels prior to ischemia. Hearts receiving GIK during the period of coronary occlusion (GIK-Pre, GIK-IV, GIK-CS) had significantly higher glucose levels. Glucose levels tended to be higher in GIK--treated hearts than in the Unmodified group. (CS = coronary sinus; IV = intravenous; R = reperfusion.)

View larger version (28K): [in this window] [in a new window]   Fig 5. . Changes in myocardial pH (pH). Hearts treated with glucose-insulin-potassium (GIK) during the 90-minute period of coronary occlusion had significantly less tissue acidosis during the periods of coronary occlusion, cardioplegic arrest, and reperfusion. (CS = coronary sinus; IV = intravenous; R = reperfusion.)

View larger version (27K): [in this window] [in a new window]   Fig 6. . Changes in wall motion scores. During the period of coronary occlusion, all hearts receiving glucose-insulin-potassium (GIK) had significantly higher wall motion scores, and wall motion scores were significantly higher in all GIK--treated hearts during reperfusion. (CS = coronary sinus; IV = intravenous; R = reperfusion.)

View larger version (15K): [in this window] [in a new window]   Fig 7. . Area of necrosis versus area of risk. Hearts receiving no glucose-insulin-potassium (GIK) had the highest area of necrosis. The area of necrosis was lower in GIK-R hearts, and the least area of necrosis was seen in hearts receiving GIK during the period of coronary ischemia (GIK-Pre, GIK-IV, GIK-CS). (CS = coronary sinus; IV = intravenous; R = reperfusion.)

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

The beneficial effects of GIK resulting from these experimental findings were seen in several studies in human hearts. Whitlow and colleagues [21] studied the effects of GIK infusions in patients with acute myocardial infarctions. Use of GIK resulted in improved global ejection fraction and significantly better regional wall motion in the infarcted area. Similar results were reported by Satler and co-workers [22] in patients with anterior myocardial infarctions. Patients treated with 48 hours of GIK infusions had improved global ventricular function and decreased segmental wall motion abnormalities. Oldfield and associates [23] documented a lower incidence of postoperative arrhythmias and hypotension in patients who received GIK infusions 12 hours prior to mitral valve replacement. Coleman and colleagues [24] studied the effects of GIK therapy in patients who required intraaortic balloon pump support to discontinue bypass after coronary artery bypass grafting. The length of intraaortic balloon pump support and the need of inotropic support were significantly decreased in the GIK--treated patients. In a study by Girard and coauthors [25] involving patients having elective coronary artery bypass grafting who were pretreated with GIK, postoperative cardiac indices were significantly higher in the GIK--treated group.

These favorable experimental and clinical studies led us to believe that GIK therapy would be most beneficial in clinical situations where a period of ischemia is followed by reperfusion. In clinical practice, this would include patients requiring urgent revascularization for unstable angina and patients with an acute coronary occlusion associated with a failed percutaneous transluminal coronary angioplasty. Our experimental model simulates the events that follow surgical revascularization after an unsuccessful percutaneous transluminal coronary angioplasty. In hearts receiving GIK infusions during the 90-minute period of coronary occlusion, there was a significant decrease in the incidence of ventricular arrhythmias (see Fig 2), less myocardial acidosis (see Fig 5), and better preservation of wall motion (see Fig 6). This contributed to lower areas of necrosis in all GIK--treated hearts (see Fig 7).

Our study has given insight into how GIK infusions may be best used in clinical practice. To be most effective, GIK therapy must be given early during ischemia. Although hearts receiving GIK infusions only during the period of reperfusion had significantly less necrosis than the Unmodified group, regional function remained depressed, and tissue pH levels and the area of necrosis were greater than in hearts receiving GIK during the period of coronary occlusion. We could find no significant difference between GIK administered intravenously or directly into the coronary sinus. This suggests that GIK need not be given through specially positioned coronary sinus catheters, thus allowing easier administration. Pretreatment with GIK did not significantly decrease the area of necrosis but did tend to result in higher wall motion scores and tissue pH values. Hence, patients with unstable angina may benefit from GIK infusions prior to coronary artery bypass grafting to prevent myocardial stunning in ischemic regions.

The results of our experimental study show that GIK effectively limits infarct size and prevents myocardial stunning. Clinical randomized studies will be necessary to determine whether these favorable experimental findings will result in decreased morbidity and mortality in patients requiring urgent and emergent coronary revascularization.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The secretarial assistance of Mrs Ellie LaBombard in the preparation of the manuscript is greatly appreciated.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Address reprint requests to Dr Lazar, The Boston University Hospital, 88 E Newton St, B404, Boston, MA 02118.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

1. Opie LH. Hypothesis: glycolytic rates control cell viability in ischemia. J Appl Cardiol 1988;3:407–14.
2. Mjos OD. Effects of free fatty acids on myocardial function and oxygen consumption in intact dogs. J Clin Invest 1971;50:1386–9.
3. Owen P, Dennis S, Opie LH. Glucose flux rate regulates onset of ischemic contracture in globally underperfused rat hearts. Circ Res 1990;60:344–54.
4. Hess ML, Okabe E, Poland J, Warner M, Stewart JR, Greenfield LJ. Glucose, insulin, potassium protection during the course of hypothermic global ischemia and reperfusion: a new proposed mechanism by the scavenging of free radicals. J Cardiovasc Pharmacol 1983;5:35–43.[Medline]
5. Sodi-Pallares D, Testelli MD, Fisleder BL, et al. Effects of an intravenous infusion of a potassium-glucose-insulin solution on the electrocardiographic signs of myocardial infarction. Am J Cardiol 1965;5:166–81.
6. Marako PR, Libby P, Sobel SE, et al. Effect of glucose-insulin-potassium infusion on myocardial infarction following experimental coronary artery occlusion. Circulation 1972;45:1160–74.[Abstract/Free Full Text]
7. Opie LH, Owen P. Effects of glucose-insulin-potassium infusions on arteriovenous differences of glucose and free fatty acids and on tissue metabolic changes in dogs with developing myocardial infarction. Am J Cardiol 1976;38:310–21.[Medline]
8. Heng MK, Norris RM, Peter T, Nisbet HD, Singh BN. The effects of glucose-insulin-potassium on experimental myocardial infarction in the dog. Cardiovasc Res 1978;12:429–35.[Medline]
9. Hearse DJ, Stewart A, Braimbridge MV. Myocardial protection during ischemic cardiac arrest. Possible deleterious effects of glucose and mannitol in coronary infusates. J Thorac Cardiovasc Surg 1976;76:16–23.[Abstract]
10. Lazar HL, Haan CK. Determinants of myocardial infarction following emergency coronary artery bypass for failed percutaneous coronary angioplasty. Ann Thorac Surg 1987;44:646–50.[Abstract]
11. Lazar HL, Faxon DP, Paone G, et al. Changing profiles of failed coronary angioplasty patients: impact on surgical results. Ann Thorac Surg 1992;53:269–73.[Abstract]
12. Lazar HL, Haan CK, Yang K, Rivers S, Bernard S, Shemin RJ. Reduction of infarct size with coronary venous retroperfusion. Circulation 1992;86(Suppl 2):353–7.[Abstract/Free Full Text]
13. Lazar HL, Yang XM, Rivers S, Treanor P, Shemin RJ. Role of percutaneous bypass in reducing infarct size following revascularization for acute coronary insufficiency. Circulation 1991;84(Suppl 3):416–21.
14. Lazar HL, Yang XM, Rivers S, Treanor P, Bernard S, Shemin RJ. Retroperfusion and balloon support to improve coronary revascularization. J Cardiovasc Surg (Torino) 1992;33:538–44.[Medline]
15. Lolley DM, Myers WO, Ray JF, Sautter RD, Tewksbury DA. Clinical experience with preoperative myocardial nutrition management. J Cardiovasc Surg (Torino) 1985;26:236–43.[Medline]
16. Rosenkranz ER, Okamoto H, Buckberg GD, Robertson JM, Vinten-Johansen J, Bugyi H. Safety of prolonged aortic clamping with blood cardioplegia. III. Aspartate enrichment of glutamate blood cardioplegia in energy-depleted hearts after ischemic and reperfusion injury. J Thorac Cardiovasc Surg 1986;91:428–35.[Abstract]
17. Lazar HL, Khoury T, Rivers S. Improved distribution of cardioplegia with pressure-controlled intermittent coronary sinus occlusion. Ann Thorac Surg 1988;46:202–7.[Abstract]
18. 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;52:512–26.
19. Gaasch WH, Zile MR, Hoshino PK, Weinberg EO, Rhodes DR, Apstein CS. Tolerance of hypertrophic heart to ischemia: studies in compensated and failing dog hearts with pressure overload hypertrophy. Circulation 1990;81:1644–53.[Abstract/Free Full Text]
20. 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.[Abstract/Free Full Text]
21. Whitlow PL, Rogers WJ, Smith LR, et al. Enhancement of left ventricular function by glucose-insulin-potassium infusion on acute myocardial infarction. Am J Cardiol 1982;49:811–20.[Medline]
22. Satler LF, Green CE, Kent KM, Pallas RS, Pearle DL, Rackley CE. Metabolic support during coronary reperfusion. Am Heart J 1987;114:54–8.[Medline]
23. 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;91:874–6.[Abstract]
24. Coleman GM, Gradinac S, Taegtmeyer 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 1):91–6.
25. Girard C, Quentin P, Bouvier H, et al. Glucose and insulin supply before cardiopulmonary bypass in cardiac surgery: a double-blind study. Ann Thorac Surg 1992;54:259–63.[Abstract]

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This Article Abstract 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 Add to Personal Folders Download to citation manager Author home page(s): Harold L. Lazar Richard J. Shemin Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lazar, H. L. Articles by Shemin, R. J. Search for Related Content PubMed PubMed Citation Articles by Lazar, H. L. Articles by Shemin, R. J.