中深度血液稀释对围体外循环期血浆S100β蛋白和NSE水平的影响
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摘要
背景与目的：20世纪50年代体外循环应用于心脏外科初期采用全血预充，临床应用后发现血液破坏严重，库血需求量大，并且引起临床输血综合征。20世纪70年代晶体胶体液混合预充成功应用于临床并得到广泛应用，大大减少了体外循环后并发症及库血用量。体外循环采用液体预充技术，降低了血液粘稠度，增加了微循环内血流速度，减少了重要器官体外循环后并发症，节约了大量库血。但是，过度的血液稀释，使组织器官缺氧水肿，导致心脑肾等重要器官功能受损。因此，需要通过实验和临床研究确定一个相对安全的合理的血液稀释程度。
多数学者认为体外循环中HCT＜20％是血液稀释的警戒线。近来有研究显示HCT15-20％的中深度血液稀释在临床上是安全的。人们对中深度血液稀释临床应用的安全性尚有争议，体外循环可导致不同程度的脑损伤，体外循环脑损伤情况是反映体外循环全身灌注是否合理的敏感指标之一。S100 β蛋白和NSE是存在于神经系统中的神经生化标志物，是评价中枢神经细胞损伤的有效检测指标。近年来，研究发现体外循环心脏手术血浆中S100 β蛋白和NSE水平明显升高，可作为体外循环心脏手术后亚临床脑损伤的有效检测指标。
本研究通过检测围体外循环期血浆S100 β蛋白和NSE水平的动态变化来探讨中深度血液稀释对脑损伤的影响，为确定合理的相对安全的血液稀释度提供临床证据。
方法：20例无神经精神系统病史拟行瓣膜置换术病人随机分为中度血液稀释
郑州大学2(X抖届硕士研究生毕业论文
中深度血液稀释对围体夕隔环期血浆sI的e蛋白和NSE水平的影响
组(对照组月CT25一30%)和中深度血液稀释组(实验组，HCT15一20%)，分别于
术前(A)体外循环开始后20分钟坦)，体外循环结束时(C)体外循环结束后30
分钟(D)，体外循环结束后5小时伍)体外循环结束后24小时(F)采集颈内静脉
血测定5100目蛋白和NSE。分别术前1天，术后1天，术后5天用简易智力评分
表(ND吐SE)对所有病人进行神经精神学评分，记录所有病人的体外循环前放血
量，术后清醒时间，术后呼吸机辅助时间，术后ICU时间，术后住院日及术后红细
胞用量。，
结果:(l)所有病例无死亡，均顺利出院，术后未发现与血液稀释有关严重
并发症，患者一般资料两组比较无统计学差异。(2)各时间点两组间5 loop蛋白
水平比较未见显著差异(P>0.05)，与基础值相比，两组5 loop蛋白水平均于体外
循环开始后20分钟有显著升高(P<0 .01)，在体外循环结束时达到峰值，与峰值相
比，体外循环结束后5小时显著下降(P<0.05)，体外循环结束后24小时恢复到术
前水平(P<习.05)。.(3)各时间点两组间NSE水平比较未见显著差异(P>.05)，
与基础值相比，体外循环开始后20分钟两组NSE有显著升高(P<0.01)，在体外
循环结束后30分钟达到峰值((P<0.01)，与峰值相比，体外循环结束后5小时显
著下降(P<0.01)，体外循环结束后24小时恢复至术前水平(P>.05)。(4)体外
循环时间和主动脉阻断时间均与5 loop蛋白峰值水平和NSE峰值水平有直线相关
关系。slOOp蛋白水平与NSE水平有直线相关关系。(5)术前1天术后l天术后
5天，两组入且以SE评分比较均无显著性差异(P>0.05)，两组均有1例病人术后1
天出现短暂认知功能障碍，其MMSE评分均<22。(6)中深度血液稀释组体外循
环前放血量显著高于中度血液稀释组(1205nU士456mIVS660d士296nd)(P<0 .01)，
术后红细胞用量显著低于中度血液稀释组(240nil月58nilVS780nil士274nil)
(P<0 .01)，两组术后清醒时间，术后ICU时间，术后呼吸机辅助时间，术后住院
日比较均无显著性差异。
结论:(1)5100日蛋白和NSE是检测体外循环早期脑损伤有效神经生化指标。
(2)体外循环可导致一过性脑损伤。(3)两组围体外循环期5100旦蛋白和和NSE
水平均无显著性差异，中深度血液稀释组所致脑损伤与中度血液稀释组对比无明
显加重。(4)中深度血液稀释结合中度低温体外循环在临床上是相对安全的。(5)
中深度血液稀释是一种良好的血液保护措施。
Background and objective:Clinical doctor applicated blood priming in cardiopulmonary hypass(CPB) in the initial stage of cardiac surgery unilizing CPB in the early 1950's. They dicovered that blood priming led to blood injuryed seriously and the demand in homologous blood increasing and the clinical synthetic symptom of transfusion. Crystal fluid and colloid fluid priming was unilized successfully and was generalized extensively in clinic in 1970's.It decreases greatly the complications after CPB and the requirment of homologous blood .The fliud priming in CPB dcreases blood viscifity and increases blood relocity in subtle circulation and reduces complications after CPB and conserves a large quality of homologous blood. But exorbitant hemodilution leads to the deficiency of oxygen and dropsy of important organs and the function of important organs (such as heart brain kidney)injuryed.Therefore ,it is important to definite a reasonable and safety hemodilution extent by means of a series of clinic and experime
nt research.
Many academicans thinks that hemodilution extent that HCT < 20% is a danger line in cardiac surgery.But recently some academicans discovered that extereme hemodilution of HCT 15-20% were safety in clinic.There is objections on safe of extereme hemodilution. CPB can lead to cerebral injury of different extent .Cerebral
injury extent after CPB is a sensitive index of reflecting entire priming of CPB. S100 B protein and NSE are neurobiochemistry markers existing in center nerve systems and are effective monitor indexs evalutating cerebral cell injury. In recently years ,it was discovered that S100β protein and NSE increased obviously after CPB, S100β protein and NSE in plasma were effective monitor indexs evaluating cerebral injury after CPB.
This study attempted to discuss the effect of extreme hemodilution on cerebral injury through assays S100β protein and NSE levels in plasma during the peri-cardipulmonary bypass and to provided evidences to definite reasonable and safe hemodilution externt.
Methods:Twenty rheumatic cardiac valve patients planned to be opereated DVR or MVR divived into moderate hemodilution group (control group , HCT25-30% in CPB) and extreme hemodilution group (experiment group ,HCT15-20%in CPB) , blood samples were taken from internal juguar rein before operation(A), 20min after the beginning of CPB(B),at the cessation of CPB(C),30minute(D)5hour(E) and 24hour(F) after CPB,to measure plasma levels of S100β protein and NSE.Mini-mental state examination(MMSE) scores was performed one day before surgery and on day one after the operation and on day five after the operation .The blood volume released before CPB ,time of wakening and mechanical ventilatory support,days in ICU and in hospital after operation ,the volume of homologous blood were recorded in tra-operatively and post-operatively.
Results: (1) All patients survived the surgery and were discharged in good condition .No complication directely attributable to the hemodilution were observed .There were no statistical difference in patient characteristics between morderate hemodilution group and extreme hemodilntion group.(2)There were no difference between two groups in the levels of S100β protein in all times (P>0.05).The levels of S100β protein increased significantly in both groups 20minute after the beginning of CPB compared with baseline values (P<0.01),and reach peak level at cessation of CPB(P<0.01),and decreased significantly 5hour after CPB compared with
peak values(P<0.05),and there were no difference with baseline value 24 hour after CPB(P<0.05).(3)There were no difference between two groups in the levels of NSE in all times (P>0.05).The levels of NSE increased significantly in both group 20minute after the beginning of CPB compared with baseline values(P<0.01) and reached peak values 30minute after CPB(P<0.01)and increased significantly 5hour after CPB compare with peak values(P<0.01),and there was no difference with baseline value 24hour after CPB(P>0.05). (4)The time of aorta blocked up and the tim
多数学者认为体外循环中HCT＜20％是血液稀释的警戒线。近来有研究显示HCT15-20％的中深度血液稀释在临床上是安全的。人们对中深度血液稀释临床应用的安全性尚有争议，体外循环可导致不同程度的脑损伤，体外循环脑损伤情况是反映体外循环全身灌注是否合理的敏感指标之一。S100 β蛋白和NSE是存在于神经系统中的神经生化标志物，是评价中枢神经细胞损伤的有效检测指标。近年来，研究发现体外循环心脏手术血浆中S100 β蛋白和NSE水平明显升高，可作为体外循环心脏手术后亚临床脑损伤的有效检测指标。
本研究通过检测围体外循环期血浆S100 β蛋白和NSE水平的动态变化来探讨中深度血液稀释对脑损伤的影响，为确定合理的相对安全的血液稀释度提供临床证据。
方法：20例无神经精神系统病史拟行瓣膜置换术病人随机分为中度血液稀释
郑州大学2(X抖届硕士研究生毕业论文
中深度血液稀释对围体夕隔环期血浆sI的e蛋白和NSE水平的影响
组(对照组月CT25一30%)和中深度血液稀释组(实验组，HCT15一20%)，分别于
术前(A)体外循环开始后20分钟坦)，体外循环结束时(C)体外循环结束后30
分钟(D)，体外循环结束后5小时伍)体外循环结束后24小时(F)采集颈内静脉
血测定5100目蛋白和NSE。分别术前1天，术后1天，术后5天用简易智力评分
表(ND吐SE)对所有病人进行神经精神学评分，记录所有病人的体外循环前放血
量，术后清醒时间，术后呼吸机辅助时间，术后ICU时间，术后住院日及术后红细
胞用量。，
结果:(l)所有病例无死亡，均顺利出院，术后未发现与血液稀释有关严重
并发症，患者一般资料两组比较无统计学差异。(2)各时间点两组间5 loop蛋白
水平比较未见显著差异(P>0.05)，与基础值相比，两组5 loop蛋白水平均于体外
循环开始后20分钟有显著升高(P<0 .01)，在体外循环结束时达到峰值，与峰值相
比，体外循环结束后5小时显著下降(P<0.05)，体外循环结束后24小时恢复到术
前水平(P<习.05)。.(3)各时间点两组间NSE水平比较未见显著差异(P>.05)，
与基础值相比，体外循环开始后20分钟两组NSE有显著升高(P<0.01)，在体外
循环结束后30分钟达到峰值((P<0.01)，与峰值相比，体外循环结束后5小时显
著下降(P<0.01)，体外循环结束后24小时恢复至术前水平(P>.05)。(4)体外
循环时间和主动脉阻断时间均与5 loop蛋白峰值水平和NSE峰值水平有直线相关
关系。slOOp蛋白水平与NSE水平有直线相关关系。(5)术前1天术后l天术后
5天，两组入且以SE评分比较均无显著性差异(P>0.05)，两组均有1例病人术后1
天出现短暂认知功能障碍，其MMSE评分均<22。(6)中深度血液稀释组体外循
环前放血量显著高于中度血液稀释组(1205nU士456mIVS660d士296nd)(P<0 .01)，
术后红细胞用量显著低于中度血液稀释组(240nil月58nilVS780nil士274nil)
(P<0 .01)，两组术后清醒时间，术后ICU时间，术后呼吸机辅助时间，术后住院
日比较均无显著性差异。
结论:(1)5100日蛋白和NSE是检测体外循环早期脑损伤有效神经生化指标。
(2)体外循环可导致一过性脑损伤。(3)两组围体外循环期5100旦蛋白和和NSE
水平均无显著性差异，中深度血液稀释组所致脑损伤与中度血液稀释组对比无明
显加重。(4)中深度血液稀释结合中度低温体外循环在临床上是相对安全的。(5)
中深度血液稀释是一种良好的血液保护措施。
Background and objective:Clinical doctor applicated blood priming in cardiopulmonary hypass(CPB) in the initial stage of cardiac surgery unilizing CPB in the early 1950's. They dicovered that blood priming led to blood injuryed seriously and the demand in homologous blood increasing and the clinical synthetic symptom of transfusion. Crystal fluid and colloid fluid priming was unilized successfully and was generalized extensively in clinic in 1970's.It decreases greatly the complications after CPB and the requirment of homologous blood .The fliud priming in CPB dcreases blood viscifity and increases blood relocity in subtle circulation and reduces complications after CPB and conserves a large quality of homologous blood. But exorbitant hemodilution leads to the deficiency of oxygen and dropsy of important organs and the function of important organs (such as heart brain kidney)injuryed.Therefore ,it is important to definite a reasonable and safety hemodilution extent by means of a series of clinic and experime
nt research.
Many academicans thinks that hemodilution extent that HCT < 20% is a danger line in cardiac surgery.But recently some academicans discovered that extereme hemodilution of HCT 15-20% were safety in clinic.There is objections on safe of extereme hemodilution. CPB can lead to cerebral injury of different extent .Cerebral
injury extent after CPB is a sensitive index of reflecting entire priming of CPB. S100 B protein and NSE are neurobiochemistry markers existing in center nerve systems and are effective monitor indexs evalutating cerebral cell injury. In recently years ,it was discovered that S100β protein and NSE increased obviously after CPB, S100β protein and NSE in plasma were effective monitor indexs evaluating cerebral injury after CPB.
This study attempted to discuss the effect of extreme hemodilution on cerebral injury through assays S100β protein and NSE levels in plasma during the peri-cardipulmonary bypass and to provided evidences to definite reasonable and safe hemodilution externt.
Methods:Twenty rheumatic cardiac valve patients planned to be opereated DVR or MVR divived into moderate hemodilution group (control group , HCT25-30% in CPB) and extreme hemodilution group (experiment group ,HCT15-20%in CPB) , blood samples were taken from internal juguar rein before operation(A), 20min after the beginning of CPB(B),at the cessation of CPB(C),30minute(D)5hour(E) and 24hour(F) after CPB,to measure plasma levels of S100β protein and NSE.Mini-mental state examination(MMSE) scores was performed one day before surgery and on day one after the operation and on day five after the operation .The blood volume released before CPB ,time of wakening and mechanical ventilatory support,days in ICU and in hospital after operation ,the volume of homologous blood were recorded in tra-operatively and post-operatively.
Results: (1) All patients survived the surgery and were discharged in good condition .No complication directely attributable to the hemodilution were observed .There were no statistical difference in patient characteristics between morderate hemodilution group and extreme hemodilntion group.(2)There were no difference between two groups in the levels of S100β protein in all times (P>0.05).The levels of S100β protein increased significantly in both groups 20minute after the beginning of CPB compared with baseline values (P<0.01),and reach peak level at cessation of CPB(P<0.01),and decreased significantly 5hour after CPB compared with
peak values(P<0.05),and there were no difference with baseline value 24 hour after CPB(P<0.05).(3)There were no difference between two groups in the levels of NSE in all times (P>0.05).The levels of NSE increased significantly in both group 20minute after the beginning of CPB compared with baseline values(P<0.01) and reached peak values 30minute after CPB(P<0.01)and increased significantly 5hour after CPB compare with peak values(P<0.01),and there was no difference with baseline value 24hour after CPB(P>0.05). (4)The time of aorta blocked up and the tim
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36. 刘建新，王明安，黄培等．小儿体外循环中采用无血预充的探讨．中国当代儿科，2001；3：265-267．
37. 徐新根，潘治，顾凯时等．中深度血液稀释在体外循环中的应用．中华胸心血管外科 1987，3：226-228．
38. Mathru M, Kleinman B, Blakeman B, et.al. Myocardial metabolism and adaptation during extreme .hemodilation in hunmans after coronary revasculatzation.Crit Care Med. 1992 Oct;20:1420-1425.