The mechanism of Blood-brain barrier disturbance after cardiopulmonary bypass in cardiovascular surgery

心血管手术体外循环后血脑屏障紊乱的机制

• 批准号: 12671474
• 负责人: ISHIDA Kazuyoshi
• 金额: $ 2.05万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671474/
• 关键词: cardiovascular surgery; neurological complication; blood-brain barrier; MAP2; GFAP; S1OOb protein; NSE; 体外循環; Neuron specific enolase; 脳浮腫; 血液脳関門破綻; 開胸返血; エバンスブルー

Marked cerebral swelling visible on magnetic resonance images has been found immediately after cardiopulmonary bypass (CPB) and may be the cause of neuropsychological disorders after cardiovascular surgery. In autopsy patients, microembolization due to cardiopulmonary bypass can be detected in the brain as lipid deposits that create small capillary and arteriolar dilations (SCADs). This lipid emboli possibly come from cardiotomy suction blood and become the cause of cerebral swelling. But this interaction has not been explored. The purposes of this study are to examine the effect of returning the cardiotomy suction blood to the blood-brain barrier in rabbit model and whether serum concentrations of S100b protein and neuron specific enolase (NSE) are predictors of cerebral damage in clinical cases of cardiovascular surgery.Animal study. Sternotomy of the rabbit was done and infusion line was cannulated into the ascending aorta via left ventricle (after heparinization). The mediastinal c … More avity was manipulated for 90 min and 75 ml suction blood was returned into the cannula under transcranial Doppler monitor on right eye (n=6). Only cannulation was done in the control rabbits (n=6). The blood-brain barrier impairment (of the right side the brain) was evaluated with the measurement of extravasated evans blue. The left side brain was dried at 110℃ for 24hr and water content was calculated. The rest of the right side of the brain was used as histopathologic evaluation. During returning the cardiotomy suction blood, multiple emboli was detected on TCD monitor and the extravasation of evans blue occur significantly in this animal. The water content was not larger than control group. There was significant difference not in MAP2 staining but in GFAP staining (increase) between groups.Human study. S100b and NSE were measured in the blood obtained at 7 time points during and after operation in eighteen patients with conventional CPB and seven with selective cerebral perfusion (SCP). Concentrations of these markers were also examined in the blood of surgical field and cell saving device. The mean values of S100b in CPB group (2.08 ± 2.00 ng ml^<-1>) and SCP group (1.46 ± 0.77 ng ml^<-1>) were largest after aortic declamp and after termination of SCP, respectively. The mean values of NSE in CPB group (29.1±14.0 ng ml^<-1>) and SCP group (31.2 ±13.6 ng ml^<-1>) were largest after termination of CPB and at the end of operation, respectively. Three patients suffered from cerebral complications but the elevation of these markers during operation was indistinguishable from those in the other patients. S100b protein and NSE concentrations in the blood of surgical field were significantly larger than those in arterial blood, while these concentrations of the blood in cell saving device were not elevated.The maneuver of returning the cardiotomy suction blood into ascending aorta become the cause of contamination of S100b protein and NSE and impairment of blood-brain barrier. Less

在心肺转流术（CPB）后立即发现磁共振图像上可见的明显脑肿胀，可能是心血管手术后神经心理障碍的原因。在尸检患者中，可在脑中检测到由心肺转流引起的微栓塞，其为脂质沉积物，可产生小毛细血管和小动脉扩张（SCAD）。这些脂质栓子可能来自心切开术后的抽血，成为脑肿胀的原因。但这种相互作用尚未被探索。本研究的目的是在兔模型中检查心切开术抽吸血液返回血脑屏障的效果，以及血清S100 b蛋白和神经元特异性烯醇化酶（NSE）浓度是否是心血管手术临床病例中脑损伤的预测因子。对家兔进行胸骨切开术，并将输注管路通过左心室插入升主动脉（肝素化后）。纵隔C ...更多信息 6例右眼在经颅多普勒监测下，将75 ml抽吸血回输至插管内。仅在对照兔（n=6）中进行插管。通过测定外渗的伊文思蓝来评价血脑屏障（右侧大脑）的损害。左侧脑在110℃下干燥24小时，并计算含水量。右侧大脑的其余部分用作组织病理学评价。在心切开术抽吸血液返回过程中，TCD监测器检测到多个栓子，该动物出现明显的伊文思蓝外渗。含水量不大于对照组。在组之间，MAP2染色没有显著差异，但GFAP染色（增加）有显著差异。对18例常规CPB和7例选择性脑灌注（SCP）患者在术中、术后7个时间点取血测定S100 b和NSE。还检查了手术区域和细胞保存装置的血液中这些标记物的浓度。CPB组和SCP组的S100 b均值分别为2.08 ± 2.00 ng ml <-1>^和1.46 ± 0.77 ng ml^<-1>，以主动脉阻断后和SCP终止后最高。CPB组和SCP组的NSE平均值分别为29.1±14.0 ng ml <-1>^和31.2 ±13.6 ng ml^<-1>，以CPB结束时和手术结束时最高。3例患者出现脑部并发症，但手术期间这些标记物的升高与其他患者无区别。术野血中S100b蛋白和NSE浓度显著高于动脉血，而细胞保存装置中血中S100b蛋白和NSE浓度未升高，术中将心切开吸引血回升主动脉操作是造成S100b蛋白和NSE污染及血脑屏障损伤的原因。少

项目成果

Ishida,Kazuyoshi et al.: "Are serum S100 protein and neuron specific enolase the predictors of cerebral damaga in cardiovascular surgery ?"Anesthesiology Abstract. (2001)

Ishida, Kazuyoshi 等人：“血清 S100 蛋白和神经元特异性烯醇化酶是心血管手术中脑损伤的预测因子吗？”麻醉学摘要。

Kazuyoshi Ishida, et al.: "Are serum S100 protein and neuron specific enolase the predictors of cerebral damage in cardiovascular surgery?"Anesthesiology. (Abstract). (2001)

Kazuyoshi Ishida 等人：“血清 S100 蛋白和神经元特异性烯醇化酶是心血管手术中脑损伤的预测因子吗？”麻醉学。

Kazuyoshi Ishida, et al.: "Are serum S100 protein and neuron specific enolase predictors of cerebral damage in cardiovascular surgery?"J Cardiothrac Vasc Anesth. (submitted to).

Kazuyoshi Ishida 等人：“血清 S100 蛋白和神经元特异性烯醇化酶是心血管手术中脑损伤的预测因子吗？”J Cardiothrac Vasc Anesth。

Kazuyoshi Ishida, et al.: "Are serum S100 protein and neuron specific enolase the predictors of cerebral damage in cardiovascular surgery?"Anesthesiology. Abstract. (2001)

Kazuyoshi Ishida 等人：“血清 S100 蛋白和神经元特异性烯醇化酶是心血管手术中脑损伤的预测因子吗？”麻醉学。

Ishida,Kazuyoshi et al.: "Are serum S100 protein and neuron specific enolase the predictors of cerebral damaga in cardiovascular surgery ?"Cardiothrac Vasc Anesth. submitted.

Ishida、Kazuyoshi 等人：“血清 S100 蛋白和神经元特异性烯醇化酶是心血管手术中脑损伤的预测因子吗？”Cardiothrac Vasc Anesth。