AIM: To explore the effects of ketamine on hemo- dynamics, plasma proinflammatory cytokine (TNF-α and IL-6) levels and nuclear factor kappa B (NF-κB) activation during polymicrobial sepsis. METHODS: Male Sprague-Dawlay rats were subjected to cecal ligation and puncture (CLP) or sham operation. The rats were randomly assigned into four equal groups: sham CLP group, CLP group, ketamine (KT)Ⅰgroup and KTⅡgroup. Thirty minutes before CLP, ketamine (5 mg/kg per hour and 10 mg/kg per hour, respectively) was infused continuously through the left femoral vein cannula in KTⅠgroup or KTⅡgroup. Sham CLP group and CLP group received 0.9% saline only (5 mL/kg per hour). The right femoral artery was cannulated to monitor mean arterial pressure (MAP) and heart rates (HR),and draw blood samples. The proinflammatory cytokine (TNF-α and IL-6) levels of plasma were measured using enzyme-linked immunosorbent assays (ELISA). The hepatic NF-κB activation was determined by Western blot and HPIAS 2000 image analysis system. Twenty hours after CLP, the rats were killed by right femoral artery phlebotomization. RESULTS: CLP produced progressive hypotension, and a first increase followed by a decrease in HR. The hypotension was prevented, and the HR was slightly steady in ketamine treated rats. TNF-α levels of plasma reached a peak value at 2 h after CLP. Ketamine (KT Ⅰgroup or KTⅡgroup) caused a significant decrease compared with CLP group at 2, 5 and 9 h time points after CLP (14.3 ± 1.9 vs 4.3 ± 0.9, 9.7 ± 1.4 vs 4.3 ± 0.9; 9.3 ± 1.5 vs 4.3 ± 0.9, 8.7 ± 1.4 vs 4.3 ± 0.9; 6.0 ± 1.5 vs 5.0 ± 1.7, 5.3 ± 0.8 vs 5.0 ± 1.7; P < 0.01, respectively). The IL-6 levels of plasma firstly ascendedand then descended in CLP group, and reached a peak value at 9 h after CLP. Ketamine (KTⅠgroup or KTⅡ group) caused a significant decrease compared with CLP group at 5, 9 or 20 h after CLP (135.0 ± 52.6 vs 60.0 ± 16.3, 112.5 ± 52.6 vs 60.0 ± 16.3; 410.0 ± 68.7 vs 62.5 ± 12.5, 250.0 ± 28.0 vs 62.5 ± 12.5; 320.0 ± 25.9 vs 52.5 ± 10.1, 215.0 ± 44.6 vs 52.5 ± 10.1; P < 0.05, respectively). The IL-6 levels of plasma in KTⅡgroup were lower than those of KTⅠgroup at 9 h after CLP (250.0 ± 28.0 vs 410.0 ± 68.7; P < 0.05). In addition, CLP increased hepatic NF-κB expression compared with sham CLP. Ketamine suppressed NF-κB activation in a dose-dependent manner at 4 h after CLP (237.7 ± 3.5 vs 246.9 ± 3.1; P < 0.05). CONCLUSION: Ketamine stabilizes the hemodynamics, attenuates the proinflammatory cytokine responses, and inhibits hepatic NF-κB activation. These findings suggest that ketamine has protective effects against polymicrobial sepsis in rats.
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