The Protective Effect Of Ketamine Against Sepsis/Septic Shock In Rats

Objective: To investigate the effect of ketamine on hemodynamics, the pro-inflammatory cytokine levels of plasma, the nuclear factor kappaB (NF-B) activition of liver, the histopathologic changes of liver, and the livability of twenty hours after CLP challenge in sepsis/septic shock rats.Methods: Male Sprague-Dawlay (SD) rats were subjected to cecal ligation and puncture (CLP, a model of polymicrobial sepsis) or sham operation. Forty rats weighing (225 25) g were randomly assigned into four equal groups: sham CLP, CLP, ketamine I (KTI) and ketamine II (KTII) groups. Thirty mintues before CLP, ketamine (5mg kg-1 h-1 and l0mgkg-1 h-1, respectively) was infused continously through the left femoral vein cannula in KTI or KTII group, Sham CLP and CLP groups receiving saline (0.9%) only. The right femoral artery was cannulated to monitor mean arterial pressure (MAP) and heart rates (HR). The pro-inflammatory cytokine levels (TNF-a and IL-6) of plasma were measured using enzyme-linked immunosorbent assays (ELISA). The NF-icB activition of liver was determined by using western blotting and HPIAS2000 image analysis system. Four or twenty hours after CLP, the animals were killed by the right femoral artery phlebotomizing, the histopathologic changes of liver were assessed by using HE dyeing.Results: CLP produced progressive hypotension, firstly ascending and following descending in HR; the hypotension were inhibited, and the HR were slightly steady in ketmine treated animals. The TNF-a levels of plasma arrived at peak value at two hours after CLP, ketmine (KTI and KTII groups) caused a significant decrease than CLP group at two and five and nine hours after CLP (P <0.01). The IL-6 levels of plasma were firstly ascending and following descending in CLP group, and arrived at peak value at nine hours after CLP, ketmine (KTI or KTII group) caused a significant decrease than CLP group at five and nine and twenty hours after CLP (P<0.05, respectively), the IL-6 levels of plasma in KTII group were lower than those of KTI group at nine hours after CLP (P<0.05, respectively). CLP increased NF-KB expression compared with sham CLP,ketamine suppressed liver NF-KB activation in a dose-dependent manner at four hours after CLP (P<0.05, respectively). At four or twenty hours after CLP, CLP produced more inflammatory cells effusion in liver gate-duct areas, the putrescence of liver cells and hyperplasia of kupffer cells, ketamine suppressed inflammatory responses. At twenty hours after CLP challenge, 27.5% of the CLP rats lived, by contrast, two ketamine-treated groups increased the livability to 41.7% and 31.3% respectively.Conclusion: Administration of ketamine has protective effect against sepsis/septic shock in rats. The mechanisms were likely to inhibit the NF-KB activition, suppress the pro-inflammatory cytokine responses, and avoid systemic inflammatory response to be happened.