Glutamine preconditioning protects against tourniquet-induced local and distant organ injury in a rodent ischemia-reperfusion model

Introduction 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. Animals and 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. Interpretation These data suggest that preconditioning with glutamine offers local and distant organ protection in the setting of tourniquet-induced IR injury.