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.
Chaudhuri
Ajay
A
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, and Kaleida Health, Buffalo, New York, USA.
Janicke
David
D
Wilson
Michael
M
Ghanim
Husam
H
Wilding
Gregory E
GE
Aljada
Ahmad
A
Dandona
Paresh
P
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