腺苷預處理在非體外循環(huán)冠狀動脈旁路移植術中心肌保護作用的初

1、腺苷預處理在非體外循環(huán)冠狀動脈旁路移植術中心肌保護作用的初步研究北京阜外心血管病醫(yī)院麻醉科 （100037）楊靜 楊大烜 葉玨 李立環(huán)【摘要】目的 探討腺苷預處理在非體外循環(huán)冠狀動脈旁路移植術（OPCAB）中的心肌保護作用。方法 擇期OPCAB患者40例，隨機分為對照組和腺苷組，每組20例。腺苷組在取乳內(nèi)動脈時經(jīng)頸內(nèi)靜脈輸注腺苷50g·kg-1·min-1，1min后上調(diào)至100g·kg-1·min-1，2min后至150g·kg-1·min-1，維持此速度至10min，輸注結(jié)束后5min開始血管吻合。對照組給予生理鹽水。連續(xù)監(jiān)測血流

2、動力學變化，并記錄麻醉誘導后10min（T0）、血運重建后30min（T1）、2h（T2）、6h（T3）、12h（T4）、24h（T5）的血流動力學參數(shù)，同時取靜脈血測定血漿肌酸激酶同功酶（CK-MB）和心肌肌鈣蛋白I（cTnI）濃度。分別于給藥前和血運重建后15min取小塊右心耳，實時熒光定量聚合酶鏈反應（Real time-PCR）法檢測TNF-和ICAM-1mRNA的相對表達量，透射電鏡觀察超微結(jié)構(gòu)的變化。結(jié)果 兩組術前一般資料比較無顯著性差異（）。血流動力學指標：與基礎值比較，兩組術中及術后血壓（BP）無顯著變化，兩組心率（HR）顯著增快（），靜脈壓（CVP）、平均肺動脈壓（MPAP）

3、和肺動脈楔壓（PCWP）有不同程度升高，外周循環(huán)阻力（SVR）降低，肺循環(huán)阻力（PVR）無顯著變化，兩組心輸出量（CO）和心指數(shù)（CI）與基礎值比較顯著升高。兩組每搏量（SV）、每搏指數(shù)（SVI）和左室每搏功指數(shù)（LVSWI）降低，右室每搏功指數(shù)（RVSWI）和右室射血分數(shù)（RVEF）無明顯變化。兩組間比較，除血運重建后2h腺苷組CO和CI顯著高于對照組（），余各循環(huán)動力學指標均無差異。兩組CK-MB的變化：與基礎值比較，兩組各點CK-MB值均升高，對照組T1T5點都顯著高于基礎值（）；腺苷組僅T2點高于基礎值（）。組間比較，腺苷組T5點顯著低于對照組（）。兩組cTnI變化：與基礎值比較，兩組

4、各時點均明顯升高（）。組間比較， T4T5點腺苷組低于對照組（）。電鏡觀察細胞超微結(jié)構(gòu)，腺苷組心肌病理改變輕于對照組。對照組血運重建后心肌細胞TNF-mRNA表達是術前的倍，而腺苷組僅為倍。同時，ICAM-1mRNA表達在對照組是倍，而腺苷組為倍。兩組比較，腺苷組TNF-和ICAM-1的mRNA表達均低于對照組（P和P）。結(jié)論 非體外循環(huán)冠狀動脈旁路移植術中存在心肌缺血及再灌注損傷并導致術后早期心功能抑制，腺苷能減少OPCAB術后CK-MB和cTnI釋放，減輕心肌組織學損傷，并可在分子水平抑制炎癥因子和粘附分子的表達，但未能顯著改善術后血流動力學?！娟P鍵詞】腺苷 預處理 非體外循環(huán)冠狀動脈旁路

5、移植術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缺血預處理對心肌的保護被認為是迄今為止最強的內(nèi)源性保護。腺苷是內(nèi)源性調(diào)節(jié)因子，在缺血預處理的心肌保護中起著核心作用，已在多種動物實驗中證實1,2。有研究表明在阻斷主動脈前經(jīng)中心靜脈外源性輸注腺苷3或給予腺苷受體激動劑同樣可達到缺血預處理的效應4。很多研究已證明腺苷在體外循環(huán)手術中能起到心肌保護作用，在非體外冠狀

17、動脈旁路移植術應用少有報道，本研究擬觀察在非體外循環(huán)冠狀動脈旁路移植術中，腺苷預處理能否起到心肌保護作用。資料與方法 病例選擇：選擇擇期初次非體外循環(huán)下冠狀動脈旁路移植術患者，年齡< 70歲，射血分數(shù)（EF）40%，多支冠狀動脈病變，收縮壓90mmHg。既往有糖尿病、哮喘或支氣管痙攣病史、病態(tài)竇房結(jié)綜合征或II、III度房室傳導阻滯、合并瓣膜病、術前兩月內(nèi)心肌梗死病人或遺傳性心臟病患者除外。所有患者實驗前兩天不食用甲基黃嘌呤（咖啡、茶、茶堿）或雙密達莫（潘生?。Ｋ谢颊唠S機分為腺苷組(n=20)或?qū)φ战M（n=20）。 麻醉方法：視病人術前情況給予適當?shù)男难芩幬?，術前2h口服安定10m

18、g，術前30min肌肉注射嗎啡10mg，入手術室后常規(guī)監(jiān)測心電圖和脈搏血氧飽和度，行外周靜脈和橈動脈穿刺。以依托咪酯0.3mg / kg，哌庫溴銨0.15 mg / kg，芬太尼1020mg / kg麻醉誘導。氣管插管后以丙泊酚持續(xù)靜脈輸注（TCI血漿靶濃度0.51 mg/ml），間斷注射芬太尼和阿端維持麻醉。氣管插管后行頸內(nèi)靜脈穿刺置漂浮導管，鎖骨下靜脈穿刺置三腔靜脈導管。 給藥方法：取乳內(nèi)動脈時腺苷組經(jīng)頸內(nèi)靜脈導管輸注腺苷50g·kg-1·min-1，1min 后上調(diào)至100g·kg-1·min-1，2min后上調(diào)至150g·kg-1

19、83;min-1，維持此速度至10min。輸注過程中如遇收縮壓低于90mmHg，加快補液速度和/或間斷注射去甲腎上腺素4-8g維持收縮壓90mmHg以上。對照組輸注生理鹽水。輸注結(jié)束后5min以上開始血管吻合。 檢測指標：循環(huán)指標：于麻醉誘導后10min（T0）、開側(cè)壁鉗后30min（T1）、開側(cè)壁鉗后2h（T2）、6h（T3）、12h（T4）、24h（T5）記錄收縮壓（SBP）、舒張壓（DBP）、中心靜脈壓（CVP）、肺動脈收縮壓（SPAP）、舒張壓（DPAP）、肺動脈楔壓（PCWP）、心輸出量（CO）、心指數(shù)（CI）、體循環(huán)阻力（SVR）、體循環(huán)阻力指數(shù)（SVRI）、肺循環(huán)阻力（PVR）、

20、肺循環(huán)阻力指數(shù)（PVRI）、每搏量（SV）、每搏指數(shù)（SVI）、左室每搏功指數(shù)（LVSWI）、右室每搏功指數(shù)（RVSWI）及混合靜脈氧飽和度（SvO2）。生化指標：于上述六個時點取靜脈血肝素抗凝化學發(fā)光法（貝克曼化學發(fā)光儀）檢測血漿CK-MB和cTnI濃度。組織標本的制備：分別于輸注腺苷或生理鹽水前和開側(cè)壁鉗后15min取右心耳，分成兩份，一份快速液氮保存，用于Real-time PCR反應測定心肌TNF-和ICAM-1mRNA的相對表達量；一份以3% 戊二醛固定，透射電鏡觀察細胞超微結(jié)構(gòu)的變化。 TNF-和ICAM-1mRNA表達測定以Oligo6.0軟件進行引物設計（奧科生物技術公司制作）

21、。序列見表1。表1 TNF-、ICAM-1和-actin引物序列及擴增片斷長度引物名稱序列擴增片斷長度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反應體系：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反應程序為： 95變性5min，95變性30s，55退火 30s，72延伸30s，循環(huán)40次，72延伸5min。每對引物和模板均各以三個平行管反應。獲得同一樣品目的基因的CT值與-actin的CT值，計算出：CT= CT目的基因CT-actin，目的基因的相對表達量=2CT，（CT= CT未知CT參照）。 統(tǒng)計學處理 采用統(tǒng)計軟件進行分析。計量資料以

23、均數(shù)±標準差（±s）表示，組間比較采用單因素方差分析，組內(nèi)比較采用雙因素方差分析，P<0.05 為差異有統(tǒng)計學意義。結(jié) 果40例患者順利完成實驗。圍術期無心肌梗死，IABP使用和死亡。 兩組術前一般資料和冠脈病變程度、搭橋數(shù)及阻斷冠脈時間比較無顯著性差異（P>0.05），見表1。表1 兩組一般資料組別年齡（歲）體重（Kg）性別比（男/女）冠脈病變支數(shù)高血壓史（有/無）陳舊心梗史（有/無）術前超聲EF（%）搭橋數(shù)（支）阻斷時間（min）對照組58±±17/3±11/96/1466±±±腺苷組±&

24、#177;14/6±12/85/15±±± 兩組血流動力學變化及比較，見表2。 兩組各時點CK-MB變化及組內(nèi)組間比較，見圖1。圖1 CK-MB的變化 （# 與T0比較P<0.01，* 組間比較P<0.05） 兩組各時點cTnI變化及組內(nèi)組間比較，圖2。 圖2 cTnI 的變化（# 與T0比較P<0.01，* 組間比較P<0.05） 心肌超微結(jié)構(gòu)兩組術前心肌纖維結(jié)構(gòu)均清晰，排列整齊，線粒體形態(tài)結(jié)構(gòu)正常（見圖3）。對照組術后部分肌節(jié)短縮、肌原纖維結(jié)構(gòu)不清，溶解消失；部分線粒體、基質(zhì)網(wǎng)中度腫脹擴張（見圖4）。而實驗組術后心肌纖維排列整

25、齊，肌節(jié)結(jié)構(gòu)清晰，肌原纖維結(jié)構(gòu)排列清楚，僅部分肌質(zhì)網(wǎng)輕度擴張，線粒體輕度腫脹（見圖5）。圖3 透射電鏡下術前右心耳心肌組織形態(tài)（1×10000倍）圖4 透射電鏡下對照組血運重建后右心耳心肌組織形態(tài)（1×10000倍）圖5 透射電鏡下腺苷組血運重建后右心耳心肌組織形態(tài)（1×10000倍） 心肌 TNF-和ICAM-1mRNA的表達對照組血運重建后心肌細胞TNF-mRNA表達是術前的6.27倍，而腺苷組為術前的3.08倍；對照組血運重建后心肌細胞ICAM-1mRNA表達是術前的4.53倍，而腺苷組為1.62倍。兩組比較，腺苷組ICAM-1mRNA表達低于對照組，有統(tǒng)計

26、學意義（P=0.048），TNF-mRNA表達未達到統(tǒng)計學意義（P=0.07），但仍可看出腺苷組TNF-mRNA表達弱于對照組，見圖6。圖6 血運重建后心肌細胞TNF-和ICAM-1mRNA相對表達量（* 組間比較P<0.05） 術后資料兩組病人術后機械通氣時間、正性肌力藥（多巴胺5g·kg-1·min-1和腎上腺素）支持、ICU停留時間和術后住院時間均無差異，術后7天復查經(jīng)胸超聲心動圖，兩組左室EF亦無差異。表3 兩組術后資料（n=20）術后機械呼吸時間（h）ICU停留時間（h）術后住院時間（天）術后7天EF（%）正性肌力藥（人）對照組5/20腺苷組4/20討 論雖

27、然OPCABG可避免CPB、低溫、全心缺血及再灌注，心肌損傷輕，全身炎癥反應輕，但OPCABG時需要阻斷冠脈，同時手術操作引起的循環(huán)波動，以及心肌固定器對心臟的擠壓，仍會造成全心或局部心肌缺血。常溫下工作的心臟耐受缺血的能力是有限的，即使是短暫的缺血也有可能造成心肌損傷5，再血管化后的再灌注會使心肌損傷加重，所有這些因素都會造成術后早期心功能異常。本研究中兩組病人再灌注后都有不同程度的左右心功能抑制。表現(xiàn)為HR快PCWP升高，SVI、LVSWI和RVSWI降低。與其他相關研究的結(jié)果基本一致6。隨著OPCABG應用越來越普遍，如何減輕OPCABG時的心肌損傷也越來越受到重視。冠脈內(nèi)分流栓可減少缺

28、血損傷，但在易受損傷的冠脈內(nèi)使用分流栓可損傷其內(nèi)皮7。1986年Murry等1首次報道缺血預處理可提高心肌對長時間缺血的耐受性，減少心肌梗死面積。此后這種現(xiàn)象在多種屬動物實驗中得到證實。Przyklenk 等8報道OPCABG中短暫的一支血管缺血可使遠處的心肌在隨后的長時間缺血中得到保護，可減少再灌注后心肌酶的釋放。IP 已成為一種強有力的心肌保護方法。腺苷是內(nèi)源性調(diào)節(jié)因子，在缺血時快速釋放，在缺血預處理中起著核心作用，動物及臨床實驗均表明體外循環(huán)手術中外源性輸注腺苷或加入心肌停搏液中均能起到心肌保護作用9-11。在OPCABG中的應用少見報道。在本實驗中再灌注后兩組的CK-MB和cTnI均持

29、續(xù)顯著升高，但腺苷組的升高幅度顯著低于對照組，提示腺苷組病人心肌損傷輕。炎癥反應在缺血再灌注損傷中起著重要作用。TNF-和細胞表面粘附分子表達水平反映了血管內(nèi)皮細胞損傷及炎癥浸潤的程度12,13。Li等14報道靜脈持續(xù)注射腺苷可顯著抑制心肌細胞核內(nèi)NF-B活性，繼而下調(diào)TNF-mRNA的表達，減輕心肌炎性損傷，并呈劑量相關性?？聞甑?5利用大鼠在體缺血再灌注模型，也得到同樣的結(jié)論。高嵐等16g的腺苷預處理，可下調(diào)心肌TNF-和ICAM-1mRNA的表達。但在Wei等10的臨床研究中，雖然腺苷預處理（140g·kg-1·min-1，輸注7min）改善了體外循環(huán)冠狀動脈旁路移

30、植術后血流動力學，但沒能抑制血漿細胞因子水平。為了客觀地反映細胞因子在局部的生成情況，本研究直接測定心肌組織的TNF-和ICAM-1mRNA的表達，觀察到在OPCAB術中，再灌注心肌TNF-和ICAM-1mRNA的表達增加，腺苷預處理可顯著降低再灌注心肌ICAM-1mRNA表達（P=0.048）。TNF-mRNA的表達兩組間雖未達到統(tǒng)計學意義（P=0.07），但有明顯降低趨勢。同時，電鏡的超微結(jié)構(gòu)檢查也顯示出腺苷預處理可減輕再灌注后心肌細胞的損傷程度。遺憾的是在本實驗中，腺苷預處理未能顯著改善術后早期血流動力學和心功能。除CO和CI在再灌注后2h（T3點）腺苷組顯著高于對照組，其余指標均無差異

31、。由于兩組同時點的SVI和LVSWI平行降低，CO和CI的增加可能是HR增快和SVR降低的結(jié)果，因此CI并不能全面反映心功能狀態(tài)。這可能與所選擇的病例有關，所有患者均為三支病變，重度狹窄，但每個病人的側(cè)枝循環(huán)情況難以評估，可能會削弱腺苷預處理的效果。另外腺苷的預處理作用呈劑量相關性，隨劑量增大，作用增強，報道的最大劑量為350g·kg-1·min-1輸注10min，能改善體外循環(huán)后心功能13。通過前期預實驗，我們認為150g·kg-1·min-1的速度是大多數(shù)病人能耐受的不致引起嚴重低血壓的最大劑量，為了病人的安全采用了這一劑量，其預處理作用可能達不到血

32、流動力學和心功能明顯改善的程度，但仍可有效減少CK-MB和cTnI的釋放，降低炎性因子和黏附分子的表達，減輕心肌損傷。結(jié)論：腺苷預處理可減少非體外循環(huán)冠狀動脈旁路移植術后CK-MB和cTnI的釋放，降低炎性因子和黏附分子的表達，減輕心肌損傷，但對術后早期心功能無明顯改善。表2 血流動力學數(shù)據(jù)指標組別誘導后開側(cè)壁鉗30min術后2h術后6h 術后12h術后24hHR（次/分）對照組±±11.1#±12.2#95±13.9#±16.4#±13.0#腺苷組±±10.7#±10.1#98±13.7#&#

33、177;12.9#±9.0#SBP(mmHg)對照組±±±±±±腺苷組±±±±±±DBP(mmHg)對照組±±±±±±腺苷組±±±±±±CVP(mmHg)對照組±±±±2.2#±3.0#±3.0#腺苷組±±±±±3.1#±2.8#

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

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

36、)對照組±±±±252.1#±361.5#±425.7#腺苷組±±±353.2#±289.6#±361.5#±278.9#SVRI(dyne·s·m-2·m-5)對照組±±±±±±腺苷組±±±±±±PVR(dyne·s·m-5)對照組±±±±±±腺苷

37、組±±±±±±PVRI(dyne·s·m-2·m-5)對照組±±±±±±腺苷組±±±±±±SVI(ml·beat·m-2)對照組±±±6.7#±4.1#±±6.4#腺苷組±±7.7#±±±±LVWSI(g/ m2)對照組±13±&

38、#177;±±±腺苷組±13±±±±±RVWSI(g/ m2)對照組±±±1.1#±±±腺苷組±±±±±±RVEF(%)對照組±±±±±±腺苷組±±±±±±SvO2（%）對照組82±81±±±±±腺苷組

39、7;±±±±±參考文獻 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

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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. 柯劍娟，王焱林，李建國，等. 腺苷預處理對大鼠缺血-再灌注心肌NF

47、-B和TNF的影響. 臨床麻醉學雜志. 2004; 20(12): 738-739. 16. 高嵐，張京范，于德水，等. 腺苷對離體心臟再灌注后炎性因子TNF-、ICAM-1mRNA表達的影響. 中華麻醉學雜志. 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