A single small dose of ketamine prevents lung injury following hepatic ischemia-reperfusion in rabbits

BackgroundPrevious studies demonstrated that large-dose ketamine alleviated lipopolysaccharide-induced lung injury. We investigated whether a single small dose of ketamine could attenuate lung injury induced by hepatic ischemia-reperfusion (HIR) and, if so its underlying mechanisms.MethodsThirty male New Zealand rabbits were randomized into three groups (n = 10 each): sham group (Group S), control group (Group C), and ketamine group (Group K). In Group S, hepatic portal vein (HPV) and inferior vena cava (IVC) were left unclamped and 0.9% saline 1 mL/kg was given intravenously. In Group K, ketamine 0.5 mg/kg (0.5 mg/mL) was given intravenously 10 minutes before cross-clamping of the HPV and the IVC. In Group C, 0.9% saline was given 10 minutes before the cross-clamping. The HPV and the IVC were cross-clamped with bulldog clamps and unclamped 60 minutes later in the Group K and the Group C. Blood pressure and pulse rate were recorded throughout the procedure. Rabbits were sacrificed 6 hours postoperatively. Lung W/D ratio was calculated and expression of tumor necrosis factor-α mRNA, intracellular adhesion molecule-1 mRNA, and nuclear factor kappa B (NF-κB)/p65 were quantitatively analyzed. Accumulation of neutrophils in lung tissues was also observed.ResultsSmall dose of ketamine alleviated the pulmonary edema, but not the systemic hypotension, induced by cross-clamping of the IVC and the HPV. Pretreatment with ketamine significantly reduced the increments of tumor necrosis factor-α mRNA, intracellular adhesion molecule-1 mRNA, and NF-κB/p65; and inhibited the aggregation of neutrophils in lung tissues following HIR.Conclusion0.5 mg/kg ketamine pretreatment showed significant protective effect on acute lung injury induced by HIR, which might be mediated by the NF-κB pathway.