七氟烷预处理对心肺转流术患者围术期血浆

细胞因子和粘附分子表达的影响

  [Abstract] Objective To investigate the effect of sevoflurane preconditioning on plasma tumor necrosis factor（TNF）-a, interleukin(IL)-6, 8, intercellular adhesion molecule (ICAM)-1 in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods 30 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomly allocated to two groups (n＝15): sevoflurane preconditioning(S) and control (C) group. In group S, sevoflurane at 1.2 MAC was inhalated for 20 min from the end of induction of anesthesia to 10 min before CPB. In group C patients were received only 100% oxygen. Blood samples were obtained from the radial artery before induction of anesthesia (T₀), 10min after aorta opened (T₁), at the discontinuation of CPB (T₂), 4h (T₃) and 24h (T₄) after CPB for determination of plasma levels of TNF-a, IL-6, 8, ICAM-1, CK-MB and cTnI. The condition of heart resuscitation was recorded. Results Plasma levels of TNF-a, IL-6, 8, ICAM-1, CK-MB and cTnI at T_1-4 were higher than that at T₀ in both groups ( P＜0.05 or ＜0.01). In group S, TNT-a, IL-6,IL-8 were significantly lower than that in group C at T_1-4 ( P＜0.05 or ＜0.01) and the levels of  ICAM-1、CK-MB、cTnI decreased at T_2-4 compared with the group C ( P＜0.05 or ＜0.01). The heart resuscitation in group S is better than that in group C (P＜0.05). Conclusion Sevoflurane preconditioning can effectively inhibit the inflammatory reaction in patients with CPB undergoing open heart operation, which may be one of the most important mechanisms of mycocardial protection caused by sevoflurane.

 [Key words] Sevoflurane; Preconditioning; Cardiopulmonary Bypass; Cytokines; Cell adhesion molecules

1986年Murry等^[1]首次提出缺血预处理（IPC）的概念，有关预处理的研究日渐增多。有研究显示，挥发性麻醉药也具有与缺血预处理相仿的机制，使心肌梗死范围减小，产生心肌保护作用，这种现象称为“挥发性麻醉药预处理”（APC）^[2],目前它已成为麻醉学研究的热点。七氟烷是一种新型卤族氟类吸入麻醉药，目前临床上广泛使用。研究表明，七氟烷预处理对心肌缺血再灌注损伤具有心肌保护作用^[3,4]，另有研究发现其对缺血再灌注大鼠心肌的保护作用与抑制炎症介质有关^[5]，七氟烷预处理对心肺转流心内直视手术患者心肌的保护作用是否也与抑制炎症介质有关尚未定论。本研究通过对肿瘤坏死因子-α（TNF-α）、白介素（IL）-6,8、细胞粘附分子（ICAM）-1浓度的测定, 从炎性反应的角度, 探讨七氟烷预处理在心肺转流心内直视手术中对心肌保护作用的可能机制，为其临床应用提供参考。

资料与方法

择期心肺转流心内直视术患者30例，男13例，女17例，ASAⅠ或Ⅱ级，年龄18~56岁，体重31~67 kg，随机分成2组（n=15）：七氟烷预处理组（S组）和对照组（C组）。所有患者术前无心内膜炎、糖尿病、高血压、高脂血症、神经系统、免疫系统和精神疾病病史，无酗酒史，肺肝肾功能未见明显异常，手术种类包括室间隔缺损（VSD）、房间隔缺损（ASD）根治术9例，二尖瓣置换术（MVR）13例，主动脉瓣置换术（DVR）8例。

麻醉前30 min肌肉注射咪达唑仑0.1 mg/kg及东莨菪碱0.2~0.3 mg。入室后建立静脉通路，DATEX- S/5监护仪(Ohmeda公司，美国)监测心电图（ECG），脉搏血氧饱和度（SpO₂）,局麻下行桡动脉穿刺置管持续监测平均动脉压（MAP）,右颈内静脉置管监测中心静脉压(CVP)。依次缓慢静脉注射咪达唑仑0.1 mg kg^-1, 芬太尼5~7 μg kg^-1及维库溴铵0.15 mg kg^-1行麻醉诱导气管插管，连接NARKOMED GS麻醉机( North American Drager公司，美国)行机械通气，维持P_ETCO₂ 35~40 mmHg（1 mmHg＝0.133kPa），术中和CPB期间以芬太尼3~5 μg kg^-1 h^-1、丙泊酚5 mg kg^-1 h^-1和维库溴铵0.12 mg kg^-1 h^-1维持麻醉和肌松,根据MAP、HR的变化调整药物剂量。肝素化后建立CPB，使用SⅢ型体外循环机器（Stockert公司，德国）和Dideco膜肺（Sorin公司，意大利）。心脏停跳采用主动脉根部灌注4℃晶体高钾停跳液，灌注流量为2.2~2.6 L min^-1 m^-2，转流期间维持平均动脉压50~80 mmHg，红细胞压积（Hct）不低于20%，维持鼻咽温度于30℃~34℃。

S组在手术开始至心肺转流前吸入浓度为2%的七氟烷(1.2MAC)（批号：5Y18 丸石制药株式会社，日本）20 min，随后给以10 min洗脱期，而C组只吸入纯氧，其余麻醉处理相同。

分别于麻醉诱导前即刻（T₀）、主动脉开放后10 min（T₁）、CPB结束即刻（T₂）、4 h（T₃）、24 h（T₄）采桡动脉血4ml，经低温离心（4℃，4000r/min, 10min）后，采用化学发光法和酶法分别检测血浆心肌肌钙蛋白I(cTnI)和肌酸激酶同工酶(CK-MB)水平（试剂盒均购自美国贝克曼公司）；ELISA法测定血浆细胞因子IL-6，8、TNF-α和ICAM-1的浓度（试剂盒购自法国Besancon Cedex公司）。并记录主动脉开放后心脏自主复跳情况。由于存在血液稀释，各指标测定结果根据Hct校正：校正值=实测值Hct×术前Hct/采样时Hct。

统计学处理  采用SPSS13.0统计软件进行统计分析，计量资料以均数±标准差（±s）表示，组内比较采用重复测量数据的方差分析，组间比较采用t检验；计数资料采用χ²检验。以P＜0.05为差异有统计学意义。

结  果

两组患者年龄、性别比、体重、手术种类构成比、CPB时间、主动脉阻断时间及最低鼻咽温度比较差异均无统计学意义（P＞0.05），见表1。

与T₀时比较，两组T_1-4TNF-α、ICAM-1、IL-6、IL-8、 CK-MB及cTnI浓度均增高（P＜0.05 或＜0.01）；与C组比较，S组 TNF-α、IL-6，8浓度T_1-4时均降低（P＜0.05或＜0.01）, ICAM-1、CK-MB、cTnI浓度T_2-4时降低（P＜0.05 或＜0.01），见表2 。

参考文献

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