乌司他丁后处理及其联合预先给药对CPB下心脏瓣膜置换术患者心肌炎性反应的影响

目的 评价乌司他丁后处理及其联合预先给药对CPB下心脏瓣膜置换术患者心肌炎性反应的影响.方法 择期行CPB下心脏瓣膜置换术患者80例,性别不限,年龄21～59岁,心功能分级Ⅱ或Ⅲ级.采用随机数字表法,将患者随机分为4组(n=20):生理盐水对照组(C组)、乌司他丁预先给药组(U1组)、乌司他丁后处理组(U2组)和乌司他丁预先给药联合后处理组(U3组).U1组于气管插管后至升主动脉阻断前10 min经中心静脉输注乌司他丁500～ 1000 U·kg-1·min-(剂量20 000U/kg)；U2组于主动脉开放前5～7 min经主动脉根部灌注乌司他丁4000～5000 U·kg-1·min-1(剂量10 000 U/kg);U3组进行乌司他丁预先给药联合后处理；C组给予等容量生理盐水.分别于升主动脉阻断前10 min(T1)、升主动脉阻断后40 min(T2)、主动脉开放后45 min(T3)和术毕(T4)时采集动脉血样,测定血浆IL- 10、IL-1、IL-6和TNF-α的浓度,并进行中性粒细胞(PMN)计数.于主动脉开放后45min时取右心耳组织,采用免疫组化法测定IL-6和IL-1β的表达.结果 与C组比较,U1组、U2组和U3组血浆IL-10浓度升高,血浆IL-1、IL-6、TNF-α的浓度和PMN计数降低,心肌组织IL-1β和IL-6表达下调(P＜ 0.05)；与U1组和U2组比较,U3组T2-4时血浆IL-10浓度升高,血浆IL-1、IL-6、TNF-α的浓度和PMN计数降低,心肌组织IL-1β和IL-6表达下调(P＜0.05).结论 乌司他丁后处理可抑制CPB下心脏瓣膜置换术患者心肌炎性反应,联合预先给药时其效应增强.

Effects of ulinastatin postconditioning and combining ulinastatin postconditioning with pretreatment on myocardial inflammatory response in patients undergoing valve replacement under CPB

Objective To investigate the effects of ulinastatin postconditioning and combining ulinastatin postconditioning with pretreatment on myocardial inflammatory response in patients undergoing cardiac valve replacement under CPB.Methods Eighty NYHA class Ⅱ or Ⅲ patients of both sexes aged 21-59 yr undergoing cardiac valve replacement under CPB were randomly divided into 4 groups ( n =20 each): group control (group C) ; group ulinastatin pretreatment ( group U1 ) ; group ulinastatin postconditioning (group U2 ) and group ulinastatin pretreatment and postconditioning combined (group U3 ).Ulinastatin 20 000 U/kg was infused via central vein at 500-1000 U·kg-1 ·min-1 after tracheal intubation until 10 min before cross-clamping of ascending aorta in groups U1 and U3.Ulinastatin 10 000 U/kg was infused into root of aorta at 4000-5000 U· kg- 1 · min- 1 at 5-7 min before declamping of aorta in groups U2 and U3.Blood samples were obtained from radial artery before cross clamping of ascending aorta,at 40 min after aortic cross-clamping,at 45 min after declamping of aorta (T3) and at the end of operation for polymorphonuclear leukocyte (PMN) count,routine analysis of blood and determination of plasma concentrations of IL-10,TNF-α,IL-1 and IL-6 (by ELISA).Myocardial specimens were obtained at 45 min after declamping of aorta for determination of IL-1β and IL-6 expression by immune-histochemistry.Results Ulinastatin pretreatment and/or postconditioning significantly increased plasma IL-10 concentration and decreased plasma IL-1,IL-6,TNF-α concentrations and PMN count and myocardial IL-1β and IL-6 expression in groups U1,U2 and U3 as compared with group C.Plasma IL-10 concentration was significantly higher and plasma IL-1,IL-6 and TNF-α concentrations,PMN count and myocardial IL-1β and IL-6 expression were lower in group U3 than in groups U1 and U2.Conclusion Ulinastatin postconditioning can inhibit myocardial imflammatory response in patients undergoing valve replacement under CPB.The protective effect can be augmented by combining ulinastatin postconditioning with pretreatment.