腺苷预处理在非体外循环冠状动脉旁路移植术中心肌保护作用的初

1、腺苷预处理在非体外循环冠状动脉旁路移植术中心肌保护作用的初步研究北京阜外心血管病医院麻醉科 （100037）杨静 杨大烜 叶珏 李立环【摘要】目的 探讨腺苷预处理在非体外循环冠状动脉旁路移植术（OPCAB）中的心肌保护作用。方法 择期OPCAB患者40例，随机分为对照组和腺苷组，每组20例。腺苷组在取乳内动脉时经颈内静脉输注腺苷50g·kg-1·min-1，1min后上调至100g·kg-1·min-1，2min后至150g·kg-1·min-1，维持此速度至10min，输注结束后5min开始血管吻合。对照组给予生理盐水。连续监测血流

2、动力学变化，并记录麻醉诱导后10min（T0）、血运重建后30min（T1）、2h（T2）、6h（T3）、12h（T4）、24h（T5）的血流动力学参数，同时取静脉血测定血浆肌酸激酶同功酶（CK-MB）和心肌肌钙蛋白I（cTnI）浓度。分别于给药前和血运重建后15min取小块右心耳，实时荧光定量聚合酶链反应（Real time-PCR）法检测TNF-和ICAM-1mRNA的相对表达量，透射电镜观察超微结构的变化。结果 两组术前一般资料比较无显著性差异（）。血流动力学指标：与基础值比较，两组术中及术后血压（BP）无显著变化，两组心率（HR）显著增快（），静脉压（CVP）、平均肺动脉压（MPAP）

3、和肺动脉楔压（PCWP）有不同程度升高，外周循环阻力（SVR）降低，肺循环阻力（PVR）无显著变化，两组心输出量（CO）和心指数（CI）与基础值比较显著升高。两组每搏量（SV）、每搏指数（SVI）和左室每搏功指数（LVSWI）降低，右室每搏功指数（RVSWI）和右室射血分数（RVEF）无明显变化。两组间比较，除血运重建后2h腺苷组CO和CI显著高于对照组（），余各循环动力学指标均无差异。两组CK-MB的变化：与基础值比较，两组各点CK-MB值均升高，对照组T1T5点都显著高于基础值（）；腺苷组仅T2点高于基础值（）。组间比较，腺苷组T5点显著低于对照组（）。两组cTnI变化：与基础值比较，两组

4、各时点均明显升高（）。组间比较， T4T5点腺苷组低于对照组（）。电镜观察细胞超微结构，腺苷组心肌病理改变轻于对照组。对照组血运重建后心肌细胞TNF-mRNA表达是术前的倍，而腺苷组仅为倍。同时，ICAM-1mRNA表达在对照组是倍，而腺苷组为倍。两组比较，腺苷组TNF-和ICAM-1的mRNA表达均低于对照组（P和P）。结论 非体外循环冠状动脉旁路移植术中存在心肌缺血及再灌注损伤并导致术后早期心功能抑制，腺苷能减少OPCAB术后CK-MB和cTnI释放，减轻心肌组织学损伤，并可在分子水平抑制炎症因子和粘附分子的表达，但未能显著改善术后血流动力学。【关键词】腺苷 预处理 非体外循环冠状动脉旁路

5、移植术Adenosine preconditioning in Off-Pump Coronary Artery Bypass Graft SurgeryYang Jing MD, PhD， Yang Daxuan MD, PhD，Ye Jue ; Li Lihuan MD, PhD【Abstract】 Object To investigate the effect of adenosine preconditioning during off-pump coronary artery bypass graft surgery (OPCAB). Methods Patients underg

6、oing elective off-pump CABG with normal ventricular function (ejection fraction 40%), and with at least three vessel disease were selected for study. The 40 patients were allocated to two groups randomly (n=20 ADO, and n=20 control). ADO group received infusion of ADO when the surgery dissociation l

7、eft internal mammary artery, through a catheter via internal jugular vein. The initial infusion rate was 50 ug·kg-1·min-1, the rate of infusion was increased every minute by 50 ug·kg-1·min-1, until the dose 150 ug·kg-1·min-1, maintain this rate to 10min. The control gro

8、up received 0.9% saline instead during the infusion period. 5min after the completion of adenosine or saline infusion protocol, revascularization began. Hemodynamic parameters were documented at following time points: T0 (10 minutes after anesthesia), T1 (30 minutes after revascularization), T2, T3,

9、 T4 and T5 (2 hours, 6 hours, 12 hours and 24 hours respectively afterwards). Blood samples were collected simultaneously for MB isoenzyme of creatine kinase （CK-MB）and cardiac troponin I (cTnI) measurement. Right atrial myocardial were harvested before and 15 minutes after revascularization respect

10、ively, for analyzing the ultrastructure and TNF-mRNA and ICAM-1mRNA expression. Results Compared with the baseline, there were no significant differences in blood pressure postoperatively, but HR increased significantly ( P<0.01)，pulmonary capillary wedge pressure (PCWP) , central venous pressure

11、（CVP）and mean pulmonary artery pressure (MPAP) increased significantly (P<0.01). Cardiac output (CO) and cardiac index (CI) increased markedly（P<0.01）. Systemic vascular resistance (SVR) , systemic vascular resistance index (SVRI) , stroke volume (SV) and stroke volume index (SVI) and left ven

12、tricular stroke work index (LVSWI) decreased significantly, while right ventricular stroke work index (RVSWI) was decreased transiently (ADO group at T1 and control group at T2 , P<0.01). Compared with the control group, CO and CI of ADO group increased markedly at T2 (). Compared with the baseli

13、ne, CK-MB of control group increased from T1 to T5 (P<0.05), that of adenosine group increased only at T2 (P<0.05), patients of ADO group released significantly less CK-MB at T5(1). Compared with the baseline, cTnI increased significantly from T1 to T5 (P<0.05) in both groups, patients of A

14、DO group released less cTnI than control group, especially at T4 and T5 point (P<0.05). The myocardial ultrastructure of control group after revascularization was damaged more seriously than that of ADO group. The expression of TNF-mRNA in ADO group decreased than the control group, but not signi

15、ficant(P=0.07). ICAM-1mRNA expression decreased significantly in ADO group (P=0.048). Conclusion The performance of OPCAB result in ischemia/reperfusion injury and heart function inhibition. Adenosine preconditioning can reduce the release of CK-MB and cTnI, also can reduce the expression of TNF-and

16、 ICAM-1mRNA, but can not improve cardiac function postoperatively. 【Keywords】Adenosine preconditioning, off-pump, Coronary Artery Bypass Surgery缺血预处理对心肌的保护被认为是迄今为止最强的内源性保护。腺苷是内源性调节因子，在缺血预处理的心肌保护中起着核心作用，已在多种动物实验中证实1,2。有研究表明在阻断主动脉前经中心静脉外源性输注腺苷3或给予腺苷受体激动剂同样可达到缺血预处理的效应4。很多研究已证明腺苷在体外循环手术中能起到心肌保护作用，在非体外冠状

17、动脉旁路移植术应用少有报道，本研究拟观察在非体外循环冠状动脉旁路移植术中，腺苷预处理能否起到心肌保护作用。资料与方法 病例选择：选择择期初次非体外循环下冠状动脉旁路移植术患者，年龄< 70岁，射血分数（EF）40%，多支冠状动脉病变，收缩压90mmHg。既往有糖尿病、哮喘或支气管痉挛病史、病态窦房结综合征或II、III度房室传导阻滞、合并瓣膜病、术前两月内心肌梗死病人或遗传性心脏病患者除外。所有患者实验前两天不食用甲基黄嘌呤（咖啡、茶、茶碱）或双密达莫（潘生丁）。所有患者随机分为腺苷组(n=20)或对照组（n=20）。 麻醉方法：视病人术前情况给予适当的心血管药物，术前2h口服安定10m

18、g，术前30min肌肉注射吗啡10mg，入手术室后常规监测心电图和脉搏血氧饱和度，行外周静脉和桡动脉穿刺。以依托咪酯0.3mg / kg，哌库溴铵0.15 mg / kg，芬太尼1020mg / kg麻醉诱导。气管插管后以丙泊酚持续静脉输注（TCI血浆靶浓度0.51 mg/ml），间断注射芬太尼和阿端维持麻醉。气管插管后行颈内静脉穿刺置漂浮导管，锁骨下静脉穿刺置三腔静脉导管。 给药方法：取乳内动脉时腺苷组经颈内静脉导管输注腺苷50g·kg-1·min-1，1min 后上调至100g·kg-1·min-1，2min后上调至150g·kg-1

19、83;min-1，维持此速度至10min。输注过程中如遇收缩压低于90mmHg，加快补液速度和/或间断注射去甲肾上腺素4-8g维持收缩压90mmHg以上。对照组输注生理盐水。输注结束后5min以上开始血管吻合。 检测指标：循环指标：于麻醉诱导后10min（T0）、开侧壁钳后30min（T1）、开侧壁钳后2h（T2）、6h（T3）、12h（T4）、24h（T5）记录收缩压（SBP）、舒张压（DBP）、中心静脉压（CVP）、肺动脉收缩压（SPAP）、舒张压（DPAP）、肺动脉楔压（PCWP）、心输出量（CO）、心指数（CI）、体循环阻力（SVR）、体循环阻力指数（SVRI）、肺循环阻力（PVR）、

20、肺循环阻力指数（PVRI）、每搏量（SV）、每搏指数（SVI）、左室每搏功指数（LVSWI）、右室每搏功指数（RVSWI）及混合静脉氧饱和度（SvO2）。生化指标：于上述六个时点取静脉血肝素抗凝化学发光法（贝克曼化学发光仪）检测血浆CK-MB和cTnI浓度。组织标本的制备：分别于输注腺苷或生理盐水前和开侧壁钳后15min取右心耳，分成两份，一份快速液氮保存，用于Real-time PCR反应测定心肌TNF-和ICAM-1mRNA的相对表达量；一份以3% 戊二醛固定，透射电镜观察细胞超微结构的变化。 TNF-和ICAM-1mRNA表达测定以Oligo6.0软件进行引物设计（奥科生物技术公司制作）

21、。序列见表1。表1 TNF-、ICAM-1和-actin引物序列及扩增片断长度引物名称序列扩增片断长度TNF-F: 5' -GCCAGCTCCCTCTATTTATG -3'R: 5'-TGGTCACCAAATCAGCATTG -3'273bpICAM-1F: 5' -TGCCCAGACATCTGTGTCCC -3'R: 5' -GCAGCGTAGGGTAAGGTTCTT- 3'336bp-actinF: 5'-CAGCACAATGAAGATCAAGATCA -3'R: 5'-CGGACTCGTCATACTC

22、CTGC -3'120bpPCR反应体系：10×Buffer（5l），MgCl2（5l），SYBRGREEN I（l），引物(3M，5l) ，dNTP（3l），Taq DNA聚合酶（l），cDNA（20l），dH2O（l）。PCR反应程序为： 95变性5min，95变性30s，55退火 30s，72延伸30s，循环40次，72延伸5min。每对引物和模板均各以三个平行管反应。获得同一样品目的基因的CT值与-actin的CT值，计算出：CT= CT目的基因CT-actin，目的基因的相对表达量=2CT，（CT= CT未知CT参照）。 统计学处理 采用统计软件进行分析。计量资料以

23、均数±标准差（±s）表示，组间比较采用单因素方差分析，组内比较采用双因素方差分析，P<0.05 为差异有统计学意义。结 果40例患者顺利完成实验。围术期无心肌梗死，IABP使用和死亡。 两组术前一般资料和冠脉病变程度、搭桥数及阻断冠脉时间比较无显著性差异（P>0.05），见表1。表1 两组一般资料组别年龄（岁）体重（Kg）性别比（男/女）冠脉病变支数高血压史（有/无）陈旧心梗史（有/无）术前超声EF（%）搭桥数（支）阻断时间（min）对照组58±±17/3±11/96/1466±±±腺苷组±&

24、#177;14/6±12/85/15±±± 两组血流动力学变化及比较，见表2。 两组各时点CK-MB变化及组内组间比较，见图1。图1 CK-MB的变化 （# 与T0比较P<0.01，* 组间比较P<0.05） 两组各时点cTnI变化及组内组间比较，图2。 图2 cTnI 的变化（# 与T0比较P<0.01，* 组间比较P<0.05） 心肌超微结构两组术前心肌纤维结构均清晰，排列整齐，线粒体形态结构正常（见图3）。对照组术后部分肌节短缩、肌原纤维结构不清，溶解消失；部分线粒体、基质网中度肿胀扩张（见图4）。而实验组术后心肌纤维排列整

25、齐，肌节结构清晰，肌原纤维结构排列清楚，仅部分肌质网轻度扩张，线粒体轻度肿胀（见图5）。图3 透射电镜下术前右心耳心肌组织形态（1×10000倍）图4 透射电镜下对照组血运重建后右心耳心肌组织形态（1×10000倍）图5 透射电镜下腺苷组血运重建后右心耳心肌组织形态（1×10000倍） 心肌 TNF-和ICAM-1mRNA的表达对照组血运重建后心肌细胞TNF-mRNA表达是术前的6.27倍，而腺苷组为术前的3.08倍；对照组血运重建后心肌细胞ICAM-1mRNA表达是术前的4.53倍，而腺苷组为1.62倍。两组比较，腺苷组ICAM-1mRNA表达低于对照组，有统计

26、学意义（P=0.048），TNF-mRNA表达未达到统计学意义（P=0.07），但仍可看出腺苷组TNF-mRNA表达弱于对照组，见图6。图6 血运重建后心肌细胞TNF-和ICAM-1mRNA相对表达量（* 组间比较P<0.05） 术后资料两组病人术后机械通气时间、正性肌力药（多巴胺5g·kg-1·min-1和肾上腺素）支持、ICU停留时间和术后住院时间均无差异，术后7天复查经胸超声心动图，两组左室EF亦无差异。表3 两组术后资料（n=20）术后机械呼吸时间（h）ICU停留时间（h）术后住院时间（天）术后7天EF（%）正性肌力药（人）对照组5/20腺苷组4/20讨 论虽

27、然OPCABG可避免CPB、低温、全心缺血及再灌注，心肌损伤轻，全身炎症反应轻，但OPCABG时需要阻断冠脉，同时手术操作引起的循环波动，以及心肌固定器对心脏的挤压，仍会造成全心或局部心肌缺血。常温下工作的心脏耐受缺血的能力是有限的，即使是短暂的缺血也有可能造成心肌损伤5，再血管化后的再灌注会使心肌损伤加重，所有这些因素都会造成术后早期心功能异常。本研究中两组病人再灌注后都有不同程度的左右心功能抑制。表现为HR快PCWP升高，SVI、LVSWI和RVSWI降低。与其他相关研究的结果基本一致6。随着OPCABG应用越来越普遍，如何减轻OPCABG时的心肌损伤也越来越受到重视。冠脉内分流栓可减少缺

28、血损伤，但在易受损伤的冠脉内使用分流栓可损伤其内皮7。1986年Murry等1首次报道缺血预处理可提高心肌对长时间缺血的耐受性，减少心肌梗死面积。此后这种现象在多种属动物实验中得到证实。Przyklenk 等8报道OPCABG中短暂的一支血管缺血可使远处的心肌在随后的长时间缺血中得到保护，可减少再灌注后心肌酶的释放。IP 已成为一种强有力的心肌保护方法。腺苷是内源性调节因子，在缺血时快速释放，在缺血预处理中起着核心作用，动物及临床实验均表明体外循环手术中外源性输注腺苷或加入心肌停搏液中均能起到心肌保护作用9-11。在OPCABG中的应用少见报道。在本实验中再灌注后两组的CK-MB和cTnI均持

29、续显著升高，但腺苷组的升高幅度显著低于对照组，提示腺苷组病人心肌损伤轻。炎症反应在缺血再灌注损伤中起着重要作用。TNF-和细胞表面粘附分子表达水平反映了血管内皮细胞损伤及炎症浸润的程度12,13。Li等14报道静脉持续注射腺苷可显著抑制心肌细胞核内NF-B活性，继而下调TNF-mRNA的表达，减轻心肌炎性损伤，并呈剂量相关性。柯剑娟等15利用大鼠在体缺血再灌注模型，也得到同样的结论。高岚等16g的腺苷预处理，可下调心肌TNF-和ICAM-1mRNA的表达。但在Wei等10的临床研究中，虽然腺苷预处理（140g·kg-1·min-1，输注7min）改善了体外循环冠状动脉旁路移

30、植术后血流动力学，但没能抑制血浆细胞因子水平。为了客观地反映细胞因子在局部的生成情况，本研究直接测定心肌组织的TNF-和ICAM-1mRNA的表达，观察到在OPCAB术中，再灌注心肌TNF-和ICAM-1mRNA的表达增加，腺苷预处理可显著降低再灌注心肌ICAM-1mRNA表达（P=0.048）。TNF-mRNA的表达两组间虽未达到统计学意义（P=0.07），但有明显降低趋势。同时，电镜的超微结构检查也显示出腺苷预处理可减轻再灌注后心肌细胞的损伤程度。遗憾的是在本实验中，腺苷预处理未能显著改善术后早期血流动力学和心功能。除CO和CI在再灌注后2h（T3点）腺苷组显著高于对照组，其余指标均无差异

31、。由于两组同时点的SVI和LVSWI平行降低，CO和CI的增加可能是HR增快和SVR降低的结果，因此CI并不能全面反映心功能状态。这可能与所选择的病例有关，所有患者均为三支病变，重度狭窄，但每个病人的侧枝循环情况难以评估，可能会削弱腺苷预处理的效果。另外腺苷的预处理作用呈剂量相关性，随剂量增大，作用增强，报道的最大剂量为350g·kg-1·min-1输注10min，能改善体外循环后心功能13。通过前期预实验，我们认为150g·kg-1·min-1的速度是大多数病人能耐受的不致引起严重低血压的最大剂量，为了病人的安全采用了这一剂量，其预处理作用可能达不到血

32、流动力学和心功能明显改善的程度，但仍可有效减少CK-MB和cTnI的释放，降低炎性因子和黏附分子的表达，减轻心肌损伤。结论：腺苷预处理可减少非体外循环冠状动脉旁路移植术后CK-MB和cTnI的释放，降低炎性因子和黏附分子的表达，减轻心肌损伤，但对术后早期心功能无明显改善。表2 血流动力学数据指标组别诱导后开侧壁钳30min术后2h术后6h 术后12h术后24hHR（次/分）对照组±±11.1#±12.2#95±13.9#±16.4#±13.0#腺苷组±±10.7#±10.1#98±13.7#&#

33、177;12.9#±9.0#SBP(mmHg)对照组±±±±±±腺苷组±±±±±±DBP(mmHg)对照组±±±±±±腺苷组±±±±±±CVP(mmHg)对照组±±±±2.2#±3.0#±3.0#腺苷组±±±±±3.1#±2.8#

34、SPAP(mmHg)对照组±±±±4.4#±5.1#±6.4#腺苷组±±±±5.7#±5.3#±6.2#DPAP(mmHg)对照组±±±±3.1#±4.3#±腺苷组±±±±3.2#±2.9#±PCWP(mmHg)对照组±±1.8#±±2.4#±3.0#±2.3#腺苷组±±

35、7;±±±CO(L/min)对照组±±±0.8*±1.1#±1.6#±1.2#腺苷组±±±1.2*±1.7#±1.5#±1.2#CI(L·min-1·m-2) 对照组±±±0.4*±0.5#±0.8#±0.6#腺苷组±±±0.5*#±0.8#±0.7#±0.6#SVR(dyne·s·m-5

36、)对照组±±±±252.1#±361.5#±425.7#腺苷组±±±353.2#±289.6#±361.5#±278.9#SVRI(dyne·s·m-2·m-5)对照组±±±±±±腺苷组±±±±±±PVR(dyne·s·m-5)对照组±±±±±±腺苷

37、组±±±±±±PVRI(dyne·s·m-2·m-5)对照组±±±±±±腺苷组±±±±±±SVI(ml·beat·m-2)对照组±±±6.7#±4.1#±±6.4#腺苷组±±7.7#±±±±LVWSI(g/ m2)对照组±13±&

38、#177;±±±腺苷组±13±±±±±RVWSI(g/ m2)对照组±±±1.1#±±±腺苷组±±±±±±RVEF(%)对照组±±±±±±腺苷组±±±±±±SvO2（%）对照组82±81±±±±±腺苷组

39、7;±±±±±参考文献 1. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay in lethal injury in ischemic myocardium. J Circulation, 1986, 74: 1124-11362. Hori M, Kitakaze M, Takashima S, et al. Benificial Role of Adenosine in myocardial ischemic and reperfusion i

40、njury. Drug Dev Res. 1993; 28: 432-437.3. Liu CS, Thorton J, Van Winkle DM, et al. Protection against infraction is afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart. Circulation. 1991; 84: 350-356.4. Canyon SJ, Dobson GP. Pretreatment with an adenosine A1 receptor ag

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44、rdioprotective effect of adenosine pretreatment in coronary artery bypass grafting. Chest. 2001; 120: 860-865.11. Cohen G, Feder-Elituv R, Iazetta J, et al. Phase 2 Studies of Adenosine Cardioplegia. Circulation 1998; 98(19s): 225 II-233II12. Grisham MB, Granger DN, Lefer DJ. Modulation of leukocyte

45、-endothelial interactions by reactive metabolites of oxygen and nitrogen: relevance to ischemic heart disease. Free Radic Biol Med. 1998; 25(4-5): 404-433.13. Vermeiren GL, Claeys MJ, Van Bockstaele D, et al. Reperfusion injury after focal myocardial ischemia: polymophonuclear leukocyte activation a

46、nd its clinical implications. Resuscitation. 2000; 45(1): 35-61.14. Li C, Ha T, Liu L, et al. Adenosine prevents activation of transcription factor NF-kappa B and enhances activator protein-1 binding activity inischemic rat heart. Surgery. 2000; 127(2): 161-169. 15. 柯剑娟，王焱林，李建国，等. 腺苷预处理对大鼠缺血-再灌注心肌NF

47、-B和TNF的影响. 临床麻醉学杂志. 2004; 20(12): 738-739. 16. 高岚，张京范，于德水，等. 腺苷对离体心脏再灌注后炎性因子TNF-、ICAM-1mRNA表达的影响. 中华麻醉学杂志. 2001; 21(5): 305.Adenosine Preconditioning in Off-Pump Coronary Artery Bypass Graft SurgeryYang Jing MD, Yang Daxuan MD, Ye Jue ; Li Lihuan MD【Abstract】 Object To investigate the effect of aden

48、osine preconditioning during off-pump coronary artery bypass graft surgery (OPCAB). Methods Patients undergoing elective OPCAB with normal ventricular function (ejection fraction 40%), and with at least three vessel disease were selected for study. The 40 patients were allocated to two groups random

49、ly (n=20 ADO, and n=20 control). ADO group received infusion of ADO when the surgeon dissociation left internal mammary artery, through a catheter via internal jugular vein. The initial infusion rate was 50 g·kg-1·min-1, the rate of infusion was increased every minute by 50 g·kg-1

50、3;min-1, until the dose 150 g·kg-1·min-1, maintain this rate to 10min. The control group received 0.9% saline instead during the infusion period. 5min after the completion of adenosine or saline infusion protocol, revascularization began. Hemodynamic parameters were documented at following

51、 time points: T0 (10 minutes after anesthesia), T1 (30 minutes after revascularization), T2, T3, T4 and T5 (2 hours, 6 hours, 12 hours and 24 hours respectively afterwards). Blood samples were collected simultaneously for MB isoenzyme of creatine kinase （CK-MB）and cardiac troponin I (cTnI) measureme

52、nt. Right atrial myocardium were harvested before and 15 minutes after revascularization respectively, for analyzing the ultra structure and TNF-mRNA and ICAM-1mRNA expression. Results Compared with the baseline, there were no significant differences in blood pressure postoperatively, but HR increas

53、ed significantly ( P<0.01)，pulmonary capillary wedge pressure (PCWP) , central venous pressure（CVP）and mean pulmonary artery pressure (MPAP) increased significantly (P<0.01). Cardiac output (CO) and cardiac index (CI) increased markedly（P<0.01）. Systemic vascular resistance (SVR) , systemic

54、 vascular resistance index (SVRI) , stroke volume (SV) and stroke volume index (SVI) and left ventricular stroke work index (LVSWI) decreased significantly, while right ventricular stroke work index (RVSWI) was decreased transiently (ADO group at T1 and control group at T2 , P<0.01). Compared wit

55、h the control group, CO and CI of ADO group increased markedly at T2 (). Compared with the baseline, CK-MB of control group increased from T1 to T5 (P<0.05), that of adenosine group increased only at T2 (P<0.05), patients of ADO group released significantly less CK-MB at T5(1). Compared with t

56、he baseline, cTnI increased significantly from T1 to T5 (P<0.05) in both groups, patients of ADO group released less cTnI than control group, especially at T4 and T5 point (P<0.05). The myocardial ultra structure of control group after revascularization was damaged more seriously than that of

57、ADO group. The expression of TNF-and 3). Conclusion The performances of OPCAB result in ischemia/reperfusion injury and heart function inhibition. Adenosine preconditioning can reduce the release of CK-MB and cTnI, also can reduce the expression of TNF-and ICAM-1mRNA, but can not improve cardiac fun

58、ction postoperatively. 【Keywords】Adenosine preconditioning, off-pump, Coronary Artery Bypass SurgeryBackground：Ischemic preconditioning (IPC) is in experimental studies the most powerful mode of myocardial protection known. As an endogenous modulator, adenosine (ADO) takes an important role in IPC,

59、and has been confirmed in many animal studies 1, 2. Canyon and associates study indicated that infusion either ADO or adenosine receptor agonist can get the effects of IPC 4. Many studies indicated ADO preconditioning have myocardial protection effect during cardiopulmonary bypass surgery. To our kn

60、owledge, there have been no studies investigating ADO preconditioning effect during off-pump coronary artery bypass graft surgery (OPCAB). The prospective, randomized study was designed to investigate the cardioprotective effect of ADO preconditioning during OPCAB. MATERIALS AND METHODSPatients Sele

61、ctionThe investigation was approved by hospital ethics committee. Forty patients with multiple-vessel coronary artery disease and stable angina admitted to the hospital for the first time selective OPCAB were selected. The criteria in selecting patients included: age< 70 years old, ejection fraction (EF) 40%, systo