Intravenous glutamine enhances COX-2 activity giving cardioprotection.
BACKGROUND
Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning.


METHODS
Male New Zealand white rabbits (n = 28) received either 0.5 g/kg glutamine in 0.9% saline or saline only in divided doses for 3 d. The large marginal branch of the left coronary was occluded for 30 min; cardiac function was assessed during 3 h of reperfusion, and infarct size was measured. 6-Keto-PGF-1alpha, nitrate, and malonaldehyde serum levels were determined. Hearts were taken from a further group of pretreated rabbits (n = 10) to assess myocardial COX-2 and HSP72 levels.


RESULTS
Glutamine pretreatment resulted in a 39% reduction in infarct size (30.7 +/- 2.0% versus 50.4 +/- 2.1% controls; P < 0.01). Myocardial COX-2 levels were significantly elevated with pretreatment (P < 0.05) and were mirrored by higher serum 6-keto-PGF-1alpha levels prior to ischemia (69 +/- 13 versus 18 +/- 21 pg/mL in controls, P = 0.027). There was no significant difference in myocardial HSP72 or serum nitrate levels following pretreatment, or malonaldehyde levels during reperfusion.


CONCLUSIONS
Glutamine pretreatment confers anti-infarct protection through up-regulation of COX-2, a key mediator of delayed preconditioning protection. Previous confirmation of its clinical safety profile at these doses suggests an acceptable strategy for inducing preconditioning for perioperative protection.
McGuinness
Jonathan
J
The Royal College of Surgeons in Ireland, Department of Surgery, Beaumont Hospital, Dublin, Ireland.
Neilan
Tom G
TG
Cummins
Rob
R
Sharkasi
Adel
A
Bouchier-Hayes
David
D
Redmond
J Mark
JM
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005973:Glutamine / Q000008:administration & dosage*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006439:Hemodynamics; D007275:Injections, Intravenous; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009566:Nitrates / Q000097:blood; D011817:Rabbits
D050884:HSP72 Heat-Shock Proteins; D009566:Nitrates; D005973:Glutamine; D008315:Malondialdehyde; D015121:6-Ketoprostaglandin F1 alpha; D051546:Cyclooxygenase 2