Ketamine sedation prevents hepatic injury when given before endotoxic shock. Its effects after endotoxic shock which would have more clinical relevance, are unknown. We hypothesized that ketamine given after endotoxin would be hepatoprotective.
Methods: Male rats were injected with endotoxin (20mg/kg IP) or saline. Two hours later, ketamine (7mg/kg IP) or saline was given and rats sacrificed 5 hours later. Serum was analyzed for AST. Hepatic cyclooxygenase-2 (COX2) and hemeoxygenase-1 (HO- 1) were measured via Western immunoblot as inflammatory markers. Results are mean ± SEM (n >4/group; ANOVA).
Results: Endotoxin significantly increased serum AST, and upregulated hepatic COX-2 and HO-1 when compared to controls. Ketamine attenuated endotoxin induced hepatic injury, down regulated the pro-inflammatory enzyme COX-2 and preserved expression of the anti-inflammatory enzyme HO-1. Ketamine alone had no significant effects on these parameters when compared to controls.
Conclusion: These data indicate that ketamine exerts hepatoprotective effects even when given after endotoxic shock. These protective effects may be mediated through down regulation of COX2 and preservation of HO-1expression. Moreover, these findings could have clinical significance for patients presenting in septic shock from endotoxin.