The journal of nutrition, health & aging

, Volume 16, Issue 4, pp 365–369 | Cite as

Glutamine preconditioning protects against local and systemic injury induced by orthopaedic surgery

  • Colin G. Murphy
  • R. Stapelton
  • G. C. Chen
  • D. C. Winter
  • D. J. Bouchier-Hayes
JNHA: Clinical Trials and Aging



Long bone surgery represents a significant surgical insults, and may cause severe local and systemic sequalae following both planned and emergent surgery. Glutamine offers pharmacological modulation of injury through clinically acceptable preconditioning. This effect has not been previously demonstrated in an orthopaedic model.


The aim of the study was to test the hypothesis that glutamine preconditioning protects against the local and systemic effects of long bone trauma in a rodent model.


Thirty two adult male Sprague-Dawley rats were randomised into four groups: Control group which received trauma without preconditioning; Normal Saline preconditioning 1 hour before trauma; Glutamine preconditioning 1 hour before trauma; Glutamine preconditioning 24 hours prior to trauma. Trauma consisted of bilateral femoral fracture following intramedullary instrumentation. Blood samples were taken before the insult, and at an interval four hours following this. Bronchioalveolar lavage (BAL) was performed, with skeletal muscle and lung harvested for evaluation.


Glutamine pre-treated rats had lower Creatine Kinase levels, less creatinine elevation, and a significant reduction in neutrophil infiltration into BAL fluid. Glutamine pre-treated rats showed less muscle and lung oedema. This effect was more pronounced for the group which received glutamine 24 hours before trauma.


Preconditioning with a single bolus of intravenous glutamine prior to planned orthopaedic intervention affords loco-regional and distal organ protection. We believe these finding have significant implications for elective orthopaedic surgery where significant soft tissue and long bone manipulation is anticipated.

Key words

Orthopaedic surgery preconditioning glutamine amino acid 


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  1. 1.
    Bhattacharyya T, Iorio R, Healy WL. Rate of and risk factors for acute inpatient mortality after orthopaedic surgery. J Bone Joint Surg Am 2002;84-A(4): 562–572.PubMedGoogle Scholar
  2. 2.
    Nazon D, Abergel G, Hatem CM. Critical care in orthopedic and spine surgery. Crit Care Clin 2003; 19(1): 33–53.PubMedCrossRefGoogle Scholar
  3. 3.
    Wischmeyer PE. Glutamine and heat shock protein expression. Nutrition 2002; 18(3): 225–228.PubMedCrossRefGoogle Scholar
  4. 4.
    Ribeiro SP, Villar J, Downey GP, Edelson JD, Slutsky AS. Sodium arsenite induces heat shock protein-72 kilodalton expression in the lungs and protects rats against sepsis. Crit Care Med 1994;22(6): 922–929.PubMedCrossRefGoogle Scholar
  5. 5.
    Villar J, Edelson JD, Post M, Mullen JB, Slutsky AS. Induction of heat stress proteins is associated with decreased mortality in an animal model of acute lung injury. Am Rev Respir Dis 1993;147(1): 177–181.PubMedCrossRefGoogle Scholar
  6. 6.
    Perdrizet GA, Rewinski MJ, Schweizer RT, Scharp DW. Heat shock and recovery protects pancreatic islets from warm ischemic injury. Transplant Proc 1994;26(6): 3477–3478.PubMedGoogle Scholar
  7. 7.
    Hayashi Y, Sawa Y, Fukuyama N, Nakazawa H, Matsuda H. Preoperative glutamine administration induces heat-shock protein 70 expression and attenuates cardiopulmonary bypass-induced inflammatory response by regulating nitric oxide synthase activity. Circulation 2002;106(20): 2601–2607.PubMedCrossRefGoogle Scholar
  8. 8.
    Wischmeyer PE, Kahana M, Wolfson R, Ren H, Musch MM, Chang EB. Glutamine induces heat shock protein and protects against endotoxin shock in the rat. J Appl Physiol 2001;90(6): 2403–2410.PubMedGoogle Scholar
  9. 9.
    Timlin M, Condron C, Toomey D, Power C, Thornes B, Kearns S et al. Nacetylcysteine attenuates lung injury in a rodent model of fracture. Acta Orthop Scand 2004;75(1): 61–65.PubMedCrossRefGoogle Scholar
  10. 10.
    McCormick PH, Chen G, Tlerney S, Kelly CJ, Bouchier-Hayes DJ. Clinically relevant thermal preconditioning attenuates ischemia-reperfusion injury. J Surg Res 2003;109(1): 24–30.PubMedCrossRefGoogle Scholar
  11. 11.
    Dillon JP, Laing AJ, Chandler JR, Wang JH, McGuinness A, Redmond HP. Pravastatin attenuates tourniquet-induced skeletal muscle ischemia reperfusion injury. Acta Orthop 2006;77(1): 27–32.PubMedCrossRefGoogle Scholar
  12. 12.
    Kearns SR, Moneley D, Murray P, Kelly C, Daly AF. Oral vitamin C attenuates acute ischaemia-reperfusion injury in skeletal muscle. J Bone Joint Surg Br 2001;83(8): 1202–1206.PubMedCrossRefGoogle Scholar
  13. 13.
    Wakai A, Winter DC, Street JT, O’sullivan RG, Wang JH, Redmond HP. Inosine attenuates tourniquet-induced skeletal muscle reperfusion injury. J Surg Res 2001;99(2): 311–315.PubMedCrossRefGoogle Scholar
  14. 14.
    Botha AJ, Moore FA, Moore EE, Sauaia A, Banerjee A, Peterson VM. Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure. J Trauma 1995;39(3): 411–417.PubMedCrossRefGoogle Scholar
  15. 15.
    Wischmeyer PE. Glutamine and heat shock protein expression. Nutrition 2002;18(3): 225–228.PubMedCrossRefGoogle Scholar
  16. 16.
    Murphy CG, Chen G, Winter DC, Bouchier-Hayes DJ. Glutamine preconditioning protects against tourniquet-induced local and distant organ injury in a rodent ischemia-reperfusion model. Acta Orthop 2007;78(4):559–566.PubMedCrossRefGoogle Scholar
  17. 17.
    Wischmeyer PE. Glutamine: the first clinically relevant pharmacological regulator of heat shock protein expression? Curr Opin Clin Nutr Metab Care 2006;9(3): 201–206.PubMedCrossRefGoogle Scholar
  18. 18.
    Wischmeyer PE. The glutamine story: where are we now? Curr Opin Crit Care 2006; 12(2): 142–148.PubMedCrossRefGoogle Scholar
  19. 19.
    Blondeau N, Widmann C, Lazdunski M, Heurteaux C. Polyunsaturated fatty acids induce ischemic and epileptic tolerance. Neuroscience 2002;109(2): 231–241.PubMedCrossRefGoogle Scholar
  20. 20.
    McGuinness J, Neilan TG, Sharkasi A, Bouchier-Hayes D, Redmond JM. Myocardial protection using an omega-3 fatty acid infusion: quantification and mechanism of action. J Thorac Cardiovasc Surg 2006;132(1): 72–79.PubMedCrossRefGoogle Scholar
  21. 21.
    Buckberg GD. Studies of hypoxemic/reoxygenation injury: I. Linkage between cardiac function and oxidant damage. J Thorac Cardiovasc Surg 1995;110(4 Pt 2): 1164–1170.PubMedCrossRefGoogle Scholar
  22. 22.
    Grace PA. Ischaemia-reperfusion injury. Br J Surg 1994;81(5): 637–647.PubMedCrossRefGoogle Scholar
  23. 23.
    Granger DN, Kvietys PR, Perry MA. Leukocyte—endothelial cell adhesion induced by ischemia and reperfusion. Can J Physiol Pharmacol 1993;71(1): 67–75.PubMedCrossRefGoogle Scholar
  24. 24.
    Houdijk AP, Rijnsburger ER, Jansen J, Wesdorp RI, Weiss JK, McCamish MA et al. Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 1998;352(9130): 772–776.PubMedCrossRefGoogle Scholar
  25. 25.
    MacBurney M, Young LS, Ziegler TR, Wilmore DW. A cost-evaluation of glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients. J Am Diet Assoc 1994; 94(11): 1263–1266.PubMedCrossRefGoogle Scholar
  26. 26.
    Morlion BJ, Stehle P, Wachtler P, Siedhoff HP, Köller M, König W et al. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: a randomized, double-blind, controlled study. Ann Surg 1998;227(2): 302–308.PubMedCrossRefGoogle Scholar

Copyright information

© Serdi and Springer Verlag France 2012

Authors and Affiliations

  • Colin G. Murphy
    • 1
    • 3
  • R. Stapelton
    • 2
  • G. C. Chen
    • 1
  • D. C. Winter
    • 1
  • D. J. Bouchier-Hayes
    • 1
  1. 1.RCSI Surgical Research UnitDublin 2Ireland
  2. 2.Department of MathematicsNational University of IrelandMaynoothIreland
  3. 3.RCSI Surgical Research UnitDublin 2Ireland

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