Intravenous Glutamine Enhances COX-2 Activity Giving Cardioprotection

• Published in: The Journal of surgical research Vol. 152; no. 1; pp. 140 - 147
• Main Authors: McGuinness, Jonathan, M.D., Ph.D, Neilan, Tom G., M.D, Cummins, Rob, B.Sc, Sharkasi, Adel, M.Sc, Bouchier-Hayes, David, M.Ch., F.R.C.S.I, Redmond, J. Mark, M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2009; Elsevier
• Subjects: 6-Ketoprostaglandin F1 alpha - blood; Animals; Biological and medical sciences; Cardiology. Vascular system; Coronary heart disease; COX-2; Cyclooxygenase 2 - metabolism; General aspects; glutamine; Glutamine - administration & dosage; Heart; Hemodynamics; HSP72 Heat-Shock Proteins - metabolism; Injections, Intravenous; Ischemic Preconditioning, Myocardial; Male; Malondialdehyde - blood; Medical sciences; myocardial ischemia-reperfusion; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocardium - pathology; Nitrates - blood; preconditioning; Rabbits; Surgery; myocardial ischemia-reperfusion; COX-2; glutamine; surgery; preconditioning; Intravenous administration; Enzyme; Cyclooxygenase 2; Ischemia reperfusion; Cardioprotective agent; Cardiovascular disease; Myocardial ischemia; Coronary heart disease; Myocardial disease; Biological activity; Vascular disease; Medicine; Treatment; Aminoacid; Surgery; Oxidoreductases; Preconditioning; Glutamine
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2008.03.045

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. Materials and 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.