Effect of modified glucose-insulin-potassium on free fatty acids, matrix metalloproteinase, and myoglobin in ST-elevation myocardial infarction.
Insulin has a free fatty acid (FFA)-suppressive effect, vascular endothelial growth factor (VEGF)- and matrix metalloproteinase (MMP)-lowering effect, and a potential myocardial-protective effect. Whether low-dose insulin exerts these effects in patients with acute myocardial infarction (MI) was investigated. Thirty-two patients administered thrombolytics and heparin were randomly assigned to a modified glucose-insulin-potassium (GIK) regimen (insulin 2.5 U/hour, dextrose and potassium titrated to prevent hyperglycemia) or normal saline solution and potassium (controls) for 48 hours. Plasma FFA, serum VEGF, pro-MMP-1, and myoglobin were measured at baseline and sequentially for 48 hours. FFA concentrations were increased at baseline; increased further in the first 4 hours in controls (p<or=0.008), but not in the GIK group, and were higher at 4 hours in controls compared with the GIK group (p=0.0009). VEGF decreased to 7% of baseline at 2 hours and remained suppressed in both groups (p=0.0008). Pro-MMP-1 decreased in both groups (p<0.005), but this decrease was seen earlier at 2 hours in the GIK group compared with 4 hours in controls. There was no significant increase in myoglobin at 2 hours in the GIK group, whereas there was a significant increase in controls. Mean blood glucose was 131 mg/dl in controls and 124 mg/dl in the GIK group (p=NS). In conclusion, this modified GIK regimen attenuated the increase in FFA, but did not suppress it to less than the threshold for myocardial FFA uptake. It suppressed pro-MMP-1 rapidly and decreased myoglobin, whereas heparin suppressed VEGF in patients with acute MI. This provided additional rationale for conducting a trial to assess the clinical benefits of this modified GIK regimen in patients with acute MI.
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, and Kaleida Health, Buffalo, New York, USA.
Ajay
A
Chaudhuri
David
D
Janicke
Michael
M
Wilson
Husam
H
Ghanim
Gregory E
GE
Wilding
Ahmad
A
Aljada
Paresh
P
Dandona
D002317:Cardiovascular Agents / Q000494:pharmacology*; D004562:Electrocardiography; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects; D009211:Myoglobin / Q000097:blood*; D011188:Potassium / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D002317:Cardiovascular Agents; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D009211:Myoglobin; D042461:Vascular Endothelial Growth Factor A; C030396:glucose-insulin-potassium cardioplegic solution; D020781:Matrix Metalloproteinase 1; D005947:Glucose; D011188:Potassium