Anti-inflammatory effect of high-dose insulin treatment after urgent coronary revascularization surgery.
BACKGROUND
The administration of insulin has been shown to exert cardioprotective and immunomodulatory properties. Ischemia and inflammation are typical features of acute coronary syndrome, thus it was hypothesized that high-dose glucose-insulin-potassium (GIK) treatment could suppress the systemic inflammatory reaction and attenuate myocardial ischemia-reperfusion injury in patients with unstable angina pectoris after urgent coronary artery bypass surgery.


METHODS
Forty patients with unstable angina pectoris scheduled for urgent coronary artery bypass surgery and cardiopulmonary bypass were randomly assigned to receive either high-dose insulin treatment (short-acting insulin 1 IU/kg/h with 30% glucose 1.5 ml/kg/h administered separately) or control treatment (saline). Blood glucose levels were targeted to 6.0-8.0 mmol/l in both groups by adjusting the rate of glucose infusion in the GIK group and by additional insulin in the control group as needed.


RESULTS
High-dose insulin treatment was associated with significantly lower average C-reactive protein (23.8 vs. 40.1 mg/l, P= 0.008) and free fatty acid levels (0.22 vs. 0.41 mmol/l, P= < 0.001) post-operatively. Average blood glucose levels were comparable during the intensive care unit (ICU) stay (7.1 vs. 6.9 mmol/l, P= 0.5) and 95% of the control patients received supplemental insulin. The pro-inflammatory cytokine response [interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha)] did not differ between the groups and beneficial effects on myocardial injury were not detected.


CONCLUSIONS
High-dose insulin treatment has potential anti-inflammatory properties independent of its ability to lower blood glucose levels. Even profound suppression of free fatty acid levels, the attenuation of myocardial ischemia-reperfusion injury was not detected.
Koskenkari
J K
JK
Department of Anesthesiology, Division of Intensive Care, Oulu University Hospital, Oulu, Finland. juha.koskenkari@fimnet.fi
Kaukoranta
P K
PK
Rimpiläinen
J
J
Vainionpää
V
V
Ohtonen
P P
PP
Surcel
H-M
HM
Juvonen
T
T
Ala-Kokko
T I
TI
D000368:Aged; D000789:Angina, Unstable / Q000601:surgery*; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000008:administration & dosage; D004638:Emergency Treatment; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D007328:Insulin / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009204:Myocardial Revascularization / Q000379:methods; D011188:Potassium / Q000008:administration & dosage; D011446:Prospective Studies; D016896:Treatment Outcome
D015415:Biomarkers; D001786:Blood Glucose; D002314:Cardioplegic Solutions; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D015850:Interleukin-6; C030396:glucose-insulin-potassium cardioplegic solution; D016753:Interleukin-10; D002097:C-Reactive Protein; D005947:Glucose; D011188:Potassium