- 作者：Jonathan McGuinness ; Tom G. Neilan ; Rob Cummins ; Adel Sharkasi ; David Bouchier-Hayes ; J. Mark Redmond
- 关键词：surgery ; preconditioning ; glutamine ; COX-2 ; myocardial ischemia-reperfusion
- 刊名：Journal of Surgical Research
- 出版年：2009
- 出版时间：March 2009
- 年：2009
- 卷：152
- 期：1
- 页码：140-147
- 全文大小：395 K
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.