Glutamine preconditioning protects against tourniquet-induced local and distant organ injury in a rodent ischemia-reperfusion model.
BACKGROUND
Ischemia-reperfusion (IR) injury is a common surgical event, with tourniquet use being a recognized cause in orthopedic surgery. Preconditioning is a highly evolutionarily conserved endogenous protective mechanism, but finding a clinically safe, acceptable method of induction has proven difficult. Glutamine, a known inducer of the heat shock protein response, offers pharmacological modulation of injury through clinically acceptable preconditioning. Our aim was to test the hypothesis that glutamine preconditioning protects against tourniquet-induced regional and remote IR injury in a rodent model.


METHODS
40 adult male Sprague-Dawley rats were randomized into 4 groups: control, IR injury, normal saline-pretreated and IR injury, and glutamine-pretreated and IR injury. Pretreated groups received either normal saline or glutamine by intravenous bolus 24 h before injury. A bilateral hindlimb tourniquet model was used. Blood samples were analyzed, bronchioalveolar lavage (BAL) performed, and skeletal muscle and lung harvested for evaluation.


RESULTS
The glutamine-pretreated group showed significantly lower muscle myeloperoxidase (MPO) content and creatine kinase levels than the untreated or saline-pretreated injury groups. Lung tissue showed reduced MPO content and a significantly reduced neutrophil count by BAL fluid microscopy.


CONCLUSIONS
These data suggest that preconditioning with glutamine offers local and distant organ protection in the setting of tourniquet-induced IR injury.
Murphy
Colin G
CG
Department of Surgery, RCSI Research and Education Centre, Beaumont Hospital, Dublin. cmurphy@rcsi.ie
Chen
Gang
G
Winter
Desmond C
DC
Bouchier-Hayes
David J
DJ
D000818:Animals; D005973:Glutamine / Q000008:administration & dosage*; D006614:Hindlimb / Q000098:blood supply; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control; D014111:Tourniquets / Q000009:adverse effects*
D005973:Glutamine