氯胺酮对体外循环瓣膜置换术患者外周血表面黏附分子及中性粒细胞水平的影响

Effects of ketamine on the expression of adhension molecular CR3 and intracellular cAMP, cGMP of neutrophils in patients associated with CPB

目的评价氯胺酮对体外循环瓣膜置换术患者外周血表面黏附分子CR3表达水平和中性粒细胞（PMN）内炎症介质cAMP浓度的影响。方法60例体外循环（CPB）下瓣膜置换术患者随机平均分成4组，分别为对照组、氯胺酮I组、氯胺酮Ⅱ组和氯胺酮Ⅲ组（n=15），体外循环前10min经颈内静脉分别给以生理盐水（对照组）、氯胺酮I组（0．1mg／kg）、氯胺酮Ⅱ组（0．5mg／kg）和氯胺酮Ⅲ组（1．0mg／kg），并分别在麻醉诱导前即刻（T1）、体外循环开始前10min（T2）、体外循环结束即刻（13）、体外循环结束后24h（T4）不同时点从颈内静脉采血，用流式细胞仪检测CR3表达情况，高效液相色谱法测定cAMP和cGMP浓度，观察患者心率、血压的变化和血管活性药物的使用情况。结果T1，T2时点各组测量指标差异无统计学意义（P〉0．05）。13，T4时点，与对照组相比，各氯胺酮试验组患者外周血CR3表达均降低（P〈0．05），其中氯胺酮Ⅱ组和氯胺酮Ⅲ组水平更低于氯胺酮I组（P〈0．05）。13，T4时点，与对照组和氯胺酮I组相比，氯胺酮Ⅱ和氯胺酮Ⅲ组患者外周血PMN内cAMP浓度均增高（P〈0．05）。13时点，与对照组和氯胺酮I组相比，氯胺酮Ⅱ组和氯胺酮Ⅲ组患者外周血PMN内cGMP浓度均降低（P〈0．05）。T4时点，与对照组和氯胺酮I组患者相比，氯胺酮Ⅱ和氯胺酮Ⅲ组患者的平均动脉压（MAP）升高（P〈0．05）。氯胺酮Ⅲ组比其他各组术后使用更少的血管活性药（P〈0．05）。结论氯胺酮可一定程度地降低CPB患者外周血CR3的表达水平和PMN内cAMP、cGMP的浓度，从而减轻CPB时全身炎症反应。

Objective To evaluation the efficacy of ketamine on the expression of adhension molecular CR3 and intracellular cAMP, cGMP in neutrophils in patients associated with cardiopulmonary bypass （CPB）, as well as the cardiovascular function of the CPB patients. Method Sixty patients operated on with prosthetic valve replacement under CPB were randomly divided into 4 groups ： placebo, ketamine 0.1 mg/kg （ ketamine Ⅰ）, ketamine 0. 5 mg/kg （ ketamine Ⅱ ） ,ketamine 1 mg/kg（ ketamine Ⅲ） Each group included 15 cases. Venous blood samples were obtained during anesthesia induction （T1）, 10 min before CPB （T2）, end of CPB （T3） and 24 hours after operation （T4）. The expression of CR3 was measured by Flow cytometry and the concentration of cAMP/ cGMP by HPLC. Results Ketamine with various dosages decreased the expression of CR3 at the T3 and T4 in patients of ketamine groups compared with patients of placebo group （P 〈 0.05）. The dosages of ketamine Ⅱ group and ketamine Ⅲ group had more significant effect than that of ketamine Ⅰ group. The dosages of ketamine Ⅱ and ketamine Ⅲ group increased the intracellular cAMP at the T3 and T4 compared with ketamine Ⅰ group and placebo （P 〈 0.05）, respectively. However,cGMP was lower in ketamine Ⅱ and ketamine Ⅲ group than that in ketamine Ⅰ group and placebo （ P 〈 0.05） at the T3. Morever, the mean arterial blood pressure was higher in ketamine Ⅱ and ketamine Ⅲ group at T4. Only the patients of ketamine Ⅲ group required less inotropic drugs after operation. Conclusion Ketamine can reduce the expression of adhension molecular CR3 and intracellular cAMP, cGMP in neutrophils from patients associated with CPB.