Effect Of High-dose Glucose-insulin-potassium (GIK) On Acute Myocardial Infarction

Acute myocardial infarction (AMI) is one of common causes of death nowadays. Although treatment methods of AMI have developed, death, reinfarction and stroke are still important problems that patients of AMI faced with.The concept of metabolic protection to ischemic myocardium with glucose-insulin-potassium (GIK) was initially proposed in 1960's. There were conversely opinions in the effect of GIK on AMI. Meta analysis of all the clinical trials about GIK came to the conclusion that GIK had reduced AMI mortality by 18% that was only critical statistical significance. So a large-scale clinical trial is needed to assess whether GIK can reduce AMI mortality.Methods1. Recruitment of patientsThis trial is a randomized, control, open trial of GIK infusion during the first hours of AMI. 80 patients who were admitted in Department cardiology of First hospital of CMU from July 2002 to February 2004 were enrolled.2. Treatment protocolThe enrolled patients were randomized into GIK or control group. In a ratio of 1:1, 40 patients were allocated to receive high-dose GIK (25% glucose+ insulin 25u +10%kcl 30ml) at an infusion rate of 1.5ml/kg'h over 24 hours and 40 patients to control. Monitored plasma level of glucose and potassium and phlebitis.3. Following-upObserved hyperglucose, hyperkalemia, phlebitis and symptomatic hypoglucose during the phase of treatment. Followed-up all the patients at one month and recorded the incidenceof death, reinfarction and stroke. 4. StatisticsValues are presented as x s .The significance of the differences between two groupswas tested by students / test and x2 test. A two tailed P value less than 0.05 was considered siynificantResults1. Baseline characteristics of randomized patients80 patients were randomized, 40 patients were in GIK, and others in control group. All variables including drug and reperfusion therapy between two groups were no statistical significance and well matched (P>0.05).2. Results of following-up at one monthIn all patients, incidence of death, reinfarction, stroke and recurrent myocardial ischemia was 5.0% in GIK group and 15.0% in control group. A trend toward a non-significant reduction in end-point events was observed in patients allocated to GIK (P=0.26).In patients with reperfusion therapy, incidence of death, reinfarction, stroke and recurrent myocardial ischemia was 3.0% in GIK group and 14.5% in control group. There was also a non-significant reduction in end-point events in GDC group (P=0.28).3. The plasma level of glucose and potassiumThe level of potassium at 24h was 4.32 0.47mmol/l in GIK group and 3.96 0.39mmol/l in control group (P<0.01). The level of glucose at 6h was 10.89 4.52mmol/l in GIK group and 8.23 3.30mmol/l in control group (P<0.01).4. Adverse effectIn GIK group, phlebitis was reported in 7 patients (17.5%) and 2 patients were as severe phlebitis. 10 patients were needed to modulate serum glucose with insulin. Hypoglucose occurred in one patient. There was no one patient with hyperkalemia and symptoms and signs of fluid overload.DiscussionIt has been 40 years that GIK was considered as an adjunctive therapy in ischemic heart disease, but the potential role of this therapy was continuing uncertainty. So we conducted a randomized trial to evaluate the impact of a GIK solution during the first hours of AMI.Low-dose GIK probably was no good for AMI. High-dose GIK (25% glucose+ insulin 50u+80mmol/lkcl) was advocated which can maximally suppress circulating free fatty acid (FFA) levels and myocardial FFA uptake.Mechanisms of action of GIK include: Insulin promotes myocardial glucose uptake and utilization; insulin stimulates Na+-K+ATPase, increase level of potassium in cell, and suppress arrhythmia; insulin protects cardiomyocytes from apoptosis via PI3K signaling pathway.Our trial demonstrated that a trend toward a non-significant reduction in end-point events was observed in GIK group both in all patients and patients of reperfusion therapy. T...