摘要
一、前言
尽管麻醉、体外循环技术和外科手术方法不断改进和提高，脑损伤仍是困扰心脏外科的主要并发症之一。据临床观察体外循环下CABG术后脑中风的发生率3％，应用深低温停循环行主动脉弓部手术脑部并发症达7-15％。临床资料显示心脏手术后通过精神神经系统检查发现的脑损伤高达60-70％。轻微的并发症通过仔细的精神神经学检查才能发现，而明显的并发症如中风等可能会延长ICU时间及住院时间或直接影响患者的预后，还有一部分患者可能只是存在亚临床的脑损伤，而没有明显的临床表现。目前对体外循环术后脑损伤的评价多根据临床症状，通过粗略的神经系统检查结合头颅CT、MRI、脑电图等辅助检查来判断，这些辅助检查既昂贵又费时，且术后早期患者处于麻醉状态、需要呼吸机支持或循环状态不稳定，不能配合，临床检查，因此特异性的生化指标对于脑损伤的评价具有很重要的意义。神经元特异性烯醇化酶(NSE)存在于神经元细胞内，血浆中的水平与脑损伤平行，但由于也存在于红细胞和血小板内，体外循环引起的溶血可显著增加其血浆水平，降低了其脑损伤评价的特异性。肌酸磷酸激酶脑型同工酶(CK-BB)分布在胶质细胞和神经元胞浆中，可以较好的反映神经元和胶质细胞损伤的程度，但同样存在于心肌细胞内和不耐热，因而其价值有待于进一步考察。S100蛋白是一种正常存在于神经胶质细胞内的特异性蛋白，其血浆浓度不受溶血、异丙酚等影响，具有热稳定性。国外部分研究表明在脑损伤的评价中具有重要意义。本实验主要研究血浆S100蛋白在体外循环中的变化情况，初步研究其在脑损伤
军医进修学院硕士研究生毕业论文 中文摘要
评价中的意义以及与全身炎症反应的关系。
二、材料与方法
2002年3月－5月间体外循环下行。C内手术的瓣膜病患者和筒单先。0
病患者 40例，其中简单先天性心脏病 15例，瓣膜置换手术 23例，瓣膜
置换并冠状动脉搭桥2例。所有患者按标准化方式进行麻醉诱导和维持。
麻醉诱导采用静脉滴注咪哇安定、万可松、及芬太尼，麻醉维持采用间断
静滴芬太尼为主，辅以吸入异氟醚。手术期间间断给予万可松及镇静剂。
机械通气潮气量1045ml／kg，呼吸频率12q 次／分。建立标准的体外
循环，在中度血液稀释（25－30％），中度低温下（28－30C）进行心内手
术。分X4在CPB前、CPB开始20分钟、CPB结束、CPB后Zh、4h、sh、
24h、48h经由颈内静脉抽血测定血浆幻 00蛋白、TNF、IL－6、IL－8、ET－l
浓度，并对患者术后精神神经系统进行系统检查，评价患者神经系统并发
症。
三、结果
1．术后有3倒患者出现精神神经系统症状，发生率7．5％，其中二例为
精神症状，l例并发右侧大面积脑梗塞。
2．CPB开始前患者血浆引 00蛋白浓度均低于0．5 fig／l。CPB开始后患者
血浆中s10o蛋白水平迅速升高，＊m0分钟时达到O石二士O．15 U旮1，在
CPB结束时达到峰值 l．98 f 0．89fig／l，最高的达到 2．31 fig／l。CPB结束后血
浆 SI 00白水平平稳下降，术后 8小时内维持在较高的水平，在 CPB结束后
2448小时恢复到术前水平；而在存在明显神经精神系统并发症的3倒患者
CPB结束时水平明显高于其他患者，术后24）、时仍处于较高水平，发生右
侧大面积脑梗塞的患者术后血浆 SI 00蛋白水平有继发性升高。
3．血浆炎症因子与 SI 00蛋白水平呈明显的相关。
2
军医进修学院硕士研究生毕业论文 中文摘要
四、结论
1．体外循环可引起血浆S100蛋白水平明显升高，体外循环结束时处于
高峰，体外循环结束后小、时内维持在较高水平，2448小时后恢复至术前
水平。
工术后连续检查血浆SI 00蛋白对判断体外循环术后脑损伤的判断有
重要作用。
3．没有明显临床症状的患者可能存在亚临床性脑损伤。
4．体外循环引起的全身炎症反应在CPB后早期 SI 00蛋白升高中占有
重要地位，可能是引起术后早期脑损伤的主要原因。
Introduction: Despite advance in anaesthesia , cardiopulmonary bypass ( CPB ) and surgical techniques , cerebral injury remains a major source of morbidity after cardiac surgery. According to the clinical investigation, subtle cerebral injury can be detected by neuropsychometric testing in 60-70 % of patients within a week, and persist in one third of patients 6 months later. A reported incidence of stroke after CABG is 0.9-5.9%. Thoracic aortic surgery utilizing profound hypothermic circulatory arrest has an incidence of permanent neurological deficit of 7-15% and a 19-25% incidence of transient neurological injury. Currently, documentation of neurological deficit relied on crude physical examination, but the battery of neuropsychological and neurophysiological tests for cognitive dysfunction require a specified personnel to perform them, are prolonged and tedious, and are not appropriate for infants and children. Continuous electroencephalograph, transcranial Doppler, computed tomography, and magnetic resonance imaging are methods that have been used to detect cerebral injury, but this methods are expensive and time consuming, and these method are always not suitable for use immediately after cardiac surgery when patients may be unconscious, sedated and artificially ventilated, or haemodynamically unstable, and thus unable to cooperate. A specific biochemical marker for early detection of cerebral injury would be of great value. NSE has been proved to be a useful marker in evaluating the cerebral
damage, but there also exist a high concentration in the red blood cell and platelet, subtle haemolysis will greatly increase its level in serum, thus reduce its specificity in the evaluation of cerebal damage after cardiac surgery. CK-BB also exist in myocardium, the damage of myocardium during CPB and reperfusion injury will also influence its level. SI00 protein is calcium protein present in astroglial and microglial cells and is highly specific for the brain. Some studies on abroad have proven it will increase after CPB and is helpful in cerebral injury detection, especially for 'subclinical' problem such as cognitive dysfunction. Our this study is to investigate its changing pattern and the value in evaluating in neuropsychological deficit.
Material and method: From March to May in 2002, 23 valve replacement, 2 valve replacement combined with CABG and 15 simple congenital heart disease were enrolled in this study. Premedication comprised morphine ,scopolamine. Anaesthesia was induced with fentanyl (3Qug/kg), muscle relaxation was achieved with pancuronium (0.1-0.2mg/kg intravenously). Mechanical ventilation was initiated (tidal volume, 10-15ml/kg; rate, 12-15 breaths per minute) and anaesthesia was supported by inhalation 1% isoflurane. Operative monitoring was identical in all patients. Cardiopulmonary bypass was instituted using a nonpulsatile roller pump, membrane oxygenator, and a -stat acid-base protocol. Mean Pa02 was controlled under 250mmHg. All operations were performed with pump flow 2.4L / m"2/ min"1, moderate hypothermia (28-32癈), and perfusion pressure was maintained pharmacologically between 50-80 mmHg. Blood sample were taken on induction of anaesthesia, 20 minutes after initiating CPB, at the end of CPB, 2 ,4 ,8, 24, 48 hours after the termination CPB. All
sample were centrifuged for 10 minutes at 3000 rpm. The resultant serum was frozen at -20 and saved for batch analysis. Neurophysiological e xamination was taken at the first and seventh day postoperation. Serum S100 protein levels was measured using ELISA; TNF, IL-6, IL-8, ET-1 levels was measured using RIA method.
Results: There were neurological events in three patients, two of them were psychological symptoms, the third patient occurred fatally cerebral infarction. The concentrations of SI00 were in normal levels in all patients. After initiating CPB, its level increased significantly, and reached peak level at the end of CPB, then gradually decreased to normal levels at 24-48hours after the CPB in the patients without c
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