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魏昕       方才

安徽省立医院，合肥230001

Effects of Penehyclidine on Cytokins during Valve Replacement Surgery  with CPB

Xin Wei, Cai Fang

Department of Anesthesiology, <?xml:namespace prefix = st1 ns = "urn:schemas-microsoft-com:office:smarttags" />Anhui Provincial Hospital, Hefei 230001, China

ABSTRACT

Objective：Inflammation plays a pivotal role in the pathogenesis of organ dysfunction after cardiopulmonary bypass (CPB). The aim of this study was to investigate whether penehyclidine has effects on the inflammatory process and leukocytes in cardiac surgery patients undergoing CPB.

Methods：A double-blind, prospective, randomized, placebo-controlled study was undertaken to assess the effect of penehyclidine on tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-10(IL-10) levels in 20 patients undergoing CPB for elective valve replacement surgery . In 10 patients, 3 mg of penehyclidine was added to 30 min before CPB; another 10 patients received saline solution as placebo.

Results：In the control group,  IL-6 level and TNF-αwere significantly higher than the study group. IL-10 level after surgery in control group was significantly lower than study group. The progressive increment in TNF-alpha level observed was also significantly prominent in the control group.

Conclusion CPB-related whole body inflammatory response could be partially inhibited by intraoperative penehyclidine administration. This effect of penehyclidine would be helpful in preventing the well-known complications of CPB-induced systemic inflammation.

Key words: Cholinergic Antagonists ；Penehyclidine hydrochloride； Cardiopulmonary bypass； Cytokins;   

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两组间TNF-α、IL-6和IL-10浓度的比较  组内比较，C组TNF-α浓度于T1-T3各时点高于T0（P<0.01），而P组T1、T2时点TNF-α浓度较T0显著降低，其余时点与术前比较无明显变化。组间比较  TNF-α、IL-6和IL-10浓度T0时差异无统计学意义（P>0.05）,C组IL-6于T4时点高于P组（P<0.05），IL-10浓度明显低于P组。C组TNF-α浓度于T1～T4各时点均高于P组（P<0.05）。见表2

讨论

体外循环的非生理过程，血液与体外循环管道接触，以及血液动力学的急剧改变，血液中炎性介质大量增加，炎性细胞被激活并发生脱颗粒作用，可以导致全身炎症反应综合征(Systemic inflammatory response syndrome, SIRS)，从而影响心脏手术预后^[5]。尤其是缺血再灌注损伤通过大量活性氧生成、补体激活、白细胞与内皮细胞粘附，粒细胞跨内皮细胞迁移，血小板聚集，微血管通透性增加等多个过程，导致局部或全身炎性反应，可从短暂的缺血性心律失常发展为致死性多器官功能不全综合征(MODS)。参与CPB后SIRS发生发展的细胞因子是TNF-α、IL-6、IL-8、IL-10等^[2]，其严重程度主要是由促炎细胞因子（TNF-α、IL-6、IL-8等）和抗炎细胞因子（IL-10等）的平衡状态决定的。因此，研究和探讨CPB后SIRS引起的各种细胞因子的释放和变化规律，以及阐明影响其变化的机制和因素，成为近年来的研究热点。

IL-6具有多种生物活性,可诱导急性期炎性反应的产生,促进多种免疫细胞的分化及活化,同时它也是一种肝急性期反应蛋白如淀粉样蛋白A、C反应蛋白的强力诱导剂其水平升高与CPB后心功能不全有关，血清或血浆中的IL-6浓度可敏感地反映出组织损伤的程度^[3]。TNF-a可直接损伤血管内皮细胞、免疫粘附、激活中性粒细胞产生多种活性物质导致组织器官损伤^[2]。IL-10是细胞因子网络中一个重要的内源性抗炎因子，是有效的TNF-α、IL-1α、IL-6、IL-8的抑制剂，在CPB时IL-10具有心肺保护作用，在转录水平抑制多种与NFκB相关的炎性介质的基因表达，对抗TNF-α、IL-6、IL-8等促炎细胞因子的作用，减轻SIRS引起的自身组织破坏，对组织器官的损伤起到一定的保护作用^[4]。采取适当措施抑制促炎细胞因子的产生，增加抗炎细胞因子的合成，对减轻CPB后SIRS、改善患者预后具有重要的意义^[1]。

大剂量的抗胆碱药物可解除小血管痉挛，扩张血管，降低外周阻力和前负荷，改善微循环。同时抗胆碱药物还具有细胞保护作用，提高细胞对缺血、缺氧的耐受性，稳定溶酶体和线粒体等亚细胞结构，减少溶酶体酶的释放。对救治外科休克、成人呼吸窘迫综合证等危重病人具有肯定的疗效^[5]。盐酸戊乙奎醚是新一代强效抗胆碱药，抗胆碱作用强而全面，副作用少，已广泛用于心脏手术麻醉前用药，具有稳定心率、镇静、降低基础代谢率的作用。