脑苷肌肽在体外循环下心脏瓣膜置换手术中脑保护作用的研究
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摘要
目的:体外循环术后脑功能障碍是体外循环下心脏手术后的严重并发症。脑苷肌肽注射液是神经节苷脂和小分子多肽的复方制剂,神经节苷脂临床用于脑卒中,脊髓损伤等疾病的治疗,但对体外循环术后脑损伤的影响尚未见报道。因此,本研究观察体外循环下心脏瓣膜置换手术患者术中应用脑苷肌肽对血清S-100B蛋白、神经元特异性烯醇化酶(NSE)、细胞因子浓度以及脑氧代谢的影响,从而对其临床疗效进行相关评价。
方法:40例CPB下心脏瓣膜置换术患者,术前无心内膜炎、糖尿病、高血压、高脂血症、神经系统、免疫系统和精神疾病病史,肺、肝、肾功能未见明显异常,心功能(NYHA)Ⅱ～Ⅲ级,随机分为脑苷肌肽组(A组)和对照组(B组),每组20例。两组患者均在气管插管全身麻醉、中度低温和中度血液稀释体外循环下行心脏瓣膜置换术。麻醉后行桡动脉置管和右颈内静脉逆行置管至颈静脉球处。采用膜式氧合器行非搏动性灌注,动脉端装有微栓过滤器。灌注流量2.2～2.4L/(min.m~2),转流中维持平均动脉压50～80mmHg。冷血高钾停搏液停跳心脏,心包置冰保护心肌。CPB期间用α稳态处理酸碱血气状态,血流降温至鼻咽温30～31℃,降温速度为0.5～1℃/min,复温速度控制在每4～5min升高1℃。A组于麻醉诱导后静脉输注脑苷肌肽20ml(每毫升含神经节苷脂50μg、多肽3.2mg),B组给予等容积生理盐水。观察给药前后血流动力学变化。分别于给药前(T1)、CPB结束(T2)及结束后2小时(T3)、6小时(T4)、24小时(T5)各时间点采集颈内静脉球部血,采用酶联免疫吸附法(ELISA)测定血清S-100B蛋白、神经元特异性烯醇化酶(NSE)、白介素—6(IL-6)、白介素-8(IL-8)和肿瘤坏死因子—α(TNF-α)浓度。此外,分别于给药前(t1)、CPB开始降温至鼻咽温33℃(t2)、心肌血运阻断20分钟(t3)、CPB复温至鼻咽温33℃(t4)、CPB结束(t5)以及手术结束(t6)各时间点测定并计算脑氧摄取率(COE)、颈静脉球部和桡动脉血血糖浓度差(G_(a-jv))、以及颈静脉球部乳酸浓度(Lac)。
结果:(1)两组患者给药前后血流动力学均无显著变化。(2)两组S-100B蛋白及NSE浓度在CPB后均显著升高,CPB后24小时(T5)S-100B浓度基本恢复至基础值水平(T1),而NSE浓度仍高于基础值。组间比较显示B组S-100B浓度在T2、T3、T4和T5时间点均显著高于A组(P＜0.05),B组NSE浓度在T2、T3和T4时间点亦显著高于A组(P＜0.05)。(3)两组IL-6、IL-8和TNF-α浓度在CPB后均显著升高,组间比较显示B组IL-6和IL-8浓度在T3、T4和T5时间点均显著高于A组(P＜0.05),B组TNF-α浓度在T2、T3、T4和T5时间点均显著高于A组(P＜0.05)。(4)两组CPB降温及低温稳定阶段(t2和t3)脑氧摄取率和G_(a-jv)均显著低于基础值t1(P＜0.05),并在t2点A组显著高于B组(P＜0.05)。两组Lac在CPB开始后进行性升高,CPB结束达到峰值,在t4、t5及t6点A组均显著低于B组(P＜0.05)。
结论:脑苷肌肽可减少体外循环心脏瓣膜置换术病人S-100B蛋白、NSE以及细胞因子IL-6、IL-8和TNF-α的释放,提高体外循环心脏瓣膜置换术患者降温阶段脑氧摄取和脑糖利用,增加能量供应,减少乳酸生成,提示可能具有一定的脑保护作用。但本研究的结论尚需进一步的研究证实。
Objective: Cerebral dysfunction remains to be a major source of morbidity after cardiac surgery. Cattle encephalon glycoside and ignotin injection is a compound of gangliosides which used to treat stroke and spinal injury. Its effect in cardiac surgery is uncertain. The aim of this study is to investigate the cerebral protective effects of cattle encephalon glycoside and ignotin injection in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).
Material and Methods: Forty patients undergoing cardiac valve replacement with CPB were randomly divided into two groups: cattle encephalon glycoside and ignotin injection group (group A, n = 20) and control group (group B, n = 20). Patients who had medical history of endocarditis, diabetes mellitus, hypertension, hyperlipoidemia, neurologic disease, immunologic disease or mental disorder were excluded. In group A cattle encephalon glycoside and ignotin injection 20ml was given i.v. after induction of anesthesia. In group B normal saline was given instead of cattle encephalon glycoside and ignotin injection. The hemodynamic change was recorded. Blood samples were taken from jugular bulb after induction of anesthesia (T1), discontinuation of CPB (T2), 2h, 6h and 24 h (T3, T4 and T5) after discontinuation of CPB for determination of serum levels of S-100B protein , neuron specific enolase (NSE), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α(TNF-α). Blood samples were also taken after induction of anesthesia (t1) , 33℃cooling (t2) , stable hypothermic duration (t3), 33℃rewarming (t4) , discontinuation of CPB (t5) and discontinuation of operation (t6) for determination of arterial and jugular bulb blood gas, glucose and lactate (Lac) concentration. Utilization of glucose (G_(a-jv)) and cerebral extraction rate of oxygen (COE) were calculated.
Results: (1) There was no hemodynamic change during the infusion of the drug in both groups. (2) Serum levels of S-100B protein and NSE were significantly increased after CPB. At time of T5, serum levels of S-100B protein decreased to near baseline (T1), but serum levels of NSE remained high in both groups. At time of T2, T3, T4 and T5 , serum levels of S-100B protein were significantly higher in group B than in group A (P<0.05). At time of T2, T3 and T4, serum levels of NSE were significantly higher in group B than in group A (P<0.05). (3) Serum levels of IL-6, IL-8 and TNF-αwere significantly increased after CPB. At time of T3, T4 and T5, serum levels of IL-6 and IL-8 were significantly higher in group B than in group A (P<0.05). At time of T2,T3,T4 and T5, serum levels of TNF-αwere significantly higher in group B than in group A . (4) At points t2 and t3, COE and G_(a-jv) in two groups were markedly lower than that at t1 (P<0.05). At point t2, COE and G_(a-jv) were significantly higher in group A than in group B (P <0.05). Serum levels of Lac increased after beginning of CPB and reached peak value at discontinuation of CPB, At point t4, t5and t6, serum levels of Lac were significantly lower in group A than in group B (P <0.05).
Conclusion: Cattle encephalon glycoside and ignotin injection could decrease the serum levels of S-100B protein, NSE, IL-6, IL-8 and TNF-α. It may increase COE and glucose utilization during cooling and decrease the serum level of lactate. It showed some degree of cerebral protective effect during cardiac valve replacement with CPB.
方法:40例CPB下心脏瓣膜置换术患者,术前无心内膜炎、糖尿病、高血压、高脂血症、神经系统、免疫系统和精神疾病病史,肺、肝、肾功能未见明显异常,心功能(NYHA)Ⅱ～Ⅲ级,随机分为脑苷肌肽组(A组)和对照组(B组),每组20例。两组患者均在气管插管全身麻醉、中度低温和中度血液稀释体外循环下行心脏瓣膜置换术。麻醉后行桡动脉置管和右颈内静脉逆行置管至颈静脉球处。采用膜式氧合器行非搏动性灌注,动脉端装有微栓过滤器。灌注流量2.2～2.4L/(min.m~2),转流中维持平均动脉压50～80mmHg。冷血高钾停搏液停跳心脏,心包置冰保护心肌。CPB期间用α稳态处理酸碱血气状态,血流降温至鼻咽温30～31℃,降温速度为0.5～1℃/min,复温速度控制在每4～5min升高1℃。A组于麻醉诱导后静脉输注脑苷肌肽20ml(每毫升含神经节苷脂50μg、多肽3.2mg),B组给予等容积生理盐水。观察给药前后血流动力学变化。分别于给药前(T1)、CPB结束(T2)及结束后2小时(T3)、6小时(T4)、24小时(T5)各时间点采集颈内静脉球部血,采用酶联免疫吸附法(ELISA)测定血清S-100B蛋白、神经元特异性烯醇化酶(NSE)、白介素—6(IL-6)、白介素-8(IL-8)和肿瘤坏死因子—α(TNF-α)浓度。此外,分别于给药前(t1)、CPB开始降温至鼻咽温33℃(t2)、心肌血运阻断20分钟(t3)、CPB复温至鼻咽温33℃(t4)、CPB结束(t5)以及手术结束(t6)各时间点测定并计算脑氧摄取率(COE)、颈静脉球部和桡动脉血血糖浓度差(G_(a-jv))、以及颈静脉球部乳酸浓度(Lac)。
结果:(1)两组患者给药前后血流动力学均无显著变化。(2)两组S-100B蛋白及NSE浓度在CPB后均显著升高,CPB后24小时(T5)S-100B浓度基本恢复至基础值水平(T1),而NSE浓度仍高于基础值。组间比较显示B组S-100B浓度在T2、T3、T4和T5时间点均显著高于A组(P＜0.05),B组NSE浓度在T2、T3和T4时间点亦显著高于A组(P＜0.05)。(3)两组IL-6、IL-8和TNF-α浓度在CPB后均显著升高,组间比较显示B组IL-6和IL-8浓度在T3、T4和T5时间点均显著高于A组(P＜0.05),B组TNF-α浓度在T2、T3、T4和T5时间点均显著高于A组(P＜0.05)。(4)两组CPB降温及低温稳定阶段(t2和t3)脑氧摄取率和G_(a-jv)均显著低于基础值t1(P＜0.05),并在t2点A组显著高于B组(P＜0.05)。两组Lac在CPB开始后进行性升高,CPB结束达到峰值,在t4、t5及t6点A组均显著低于B组(P＜0.05)。
结论:脑苷肌肽可减少体外循环心脏瓣膜置换术病人S-100B蛋白、NSE以及细胞因子IL-6、IL-8和TNF-α的释放,提高体外循环心脏瓣膜置换术患者降温阶段脑氧摄取和脑糖利用,增加能量供应,减少乳酸生成,提示可能具有一定的脑保护作用。但本研究的结论尚需进一步的研究证实。
Objective: Cerebral dysfunction remains to be a major source of morbidity after cardiac surgery. Cattle encephalon glycoside and ignotin injection is a compound of gangliosides which used to treat stroke and spinal injury. Its effect in cardiac surgery is uncertain. The aim of this study is to investigate the cerebral protective effects of cattle encephalon glycoside and ignotin injection in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).
Material and Methods: Forty patients undergoing cardiac valve replacement with CPB were randomly divided into two groups: cattle encephalon glycoside and ignotin injection group (group A, n = 20) and control group (group B, n = 20). Patients who had medical history of endocarditis, diabetes mellitus, hypertension, hyperlipoidemia, neurologic disease, immunologic disease or mental disorder were excluded. In group A cattle encephalon glycoside and ignotin injection 20ml was given i.v. after induction of anesthesia. In group B normal saline was given instead of cattle encephalon glycoside and ignotin injection. The hemodynamic change was recorded. Blood samples were taken from jugular bulb after induction of anesthesia (T1), discontinuation of CPB (T2), 2h, 6h and 24 h (T3, T4 and T5) after discontinuation of CPB for determination of serum levels of S-100B protein , neuron specific enolase (NSE), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α(TNF-α). Blood samples were also taken after induction of anesthesia (t1) , 33℃cooling (t2) , stable hypothermic duration (t3), 33℃rewarming (t4) , discontinuation of CPB (t5) and discontinuation of operation (t6) for determination of arterial and jugular bulb blood gas, glucose and lactate (Lac) concentration. Utilization of glucose (G_(a-jv)) and cerebral extraction rate of oxygen (COE) were calculated.
Results: (1) There was no hemodynamic change during the infusion of the drug in both groups. (2) Serum levels of S-100B protein and NSE were significantly increased after CPB. At time of T5, serum levels of S-100B protein decreased to near baseline (T1), but serum levels of NSE remained high in both groups. At time of T2, T3, T4 and T5 , serum levels of S-100B protein were significantly higher in group B than in group A (P<0.05). At time of T2, T3 and T4, serum levels of NSE were significantly higher in group B than in group A (P<0.05). (3) Serum levels of IL-6, IL-8 and TNF-αwere significantly increased after CPB. At time of T3, T4 and T5, serum levels of IL-6 and IL-8 were significantly higher in group B than in group A (P<0.05). At time of T2,T3,T4 and T5, serum levels of TNF-αwere significantly higher in group B than in group A . (4) At points t2 and t3, COE and G_(a-jv) in two groups were markedly lower than that at t1 (P<0.05). At point t2, COE and G_(a-jv) were significantly higher in group A than in group B (P <0.05). Serum levels of Lac increased after beginning of CPB and reached peak value at discontinuation of CPB, At point t4, t5and t6, serum levels of Lac were significantly lower in group A than in group B (P <0.05).
Conclusion: Cattle encephalon glycoside and ignotin injection could decrease the serum levels of S-100B protein, NSE, IL-6, IL-8 and TNF-α. It may increase COE and glucose utilization during cooling and decrease the serum level of lactate. It showed some degree of cerebral protective effect during cardiac valve replacement with CPB.
引文
1 Guy M,McKhann,Maura A,et al.Stroke and encephalopathy after cardiac surgery:an update.Stroke.2006;37:562-571.
2 Mahanna EP,Blumenthal JA,White WD,et al.Defining neuropsychological dysfunction after coronary artery bypass grafting.Ann Thorac Surg.1996;61:1342-1347.
3 毕齐,张出,贺建华,等.心脏手术后早期脑血管病并发症的临床研究.中华医学杂志.1999:79:439-440.
4 皋源,张挺杰,王祥瑞,等.体外循环心脏手术后精神障碍发生率及相关因素.上海第二医科大学学报.2004:24:916-918.
5 Mocchetti I,et al.Exogenous gangliosides,neuronal plasticity and repair,and the neurotrophins.Cell Mol Life Sci.2005;62:2283o2294.
6 Alter M,et al.GM1 ganglioside for acute ischemic stroke:trial design issues.Ann N Y Acad Sci,1998;845:391-401.
7 Geisler FH,et al.Clinical trials of pharmacotherap,v for spinal cord injury.Ann N Y Acad Sci,1998;845:374-381.
8 Leon A,Lipartiti M,Seren MS,et al.Hypoxic-ischemic damage and the neuroprotective effects of GMlganglioside.Stroke.1990;21(11 Suppl):Ⅲ95-97.
9 Giacinto G,Marilyn H,Alfred T,et al.Evaluating neuroprotective agents for clinical antiischemic benefit using neuropsychological changes after cardiac surgery under cardiopulmonary bypass Methodological strategies and results of a double-blind,placebo-controlled trial of GMl ganglioside.Stroke.1996;27:858-874.
10 Redmond JM,Gillinov AM,Blue ME,et,al.The monosialoganglioside,GM1,reduces neurologic injury associated with hypothermic circulatory arrest.Surgery.1993;114:324-332.
11 Tseng EE,Brock MV,Lange MS,et al.Monosialoganglioside GM1 inhibits neurotoxicity after hypothermic circulatory arrest.Surgery.1998;124:298-306.
12 Mocchetti I.Exogenous gangliosides,neuronal plasticity and repair,and the neurotrophins.Mol Life Sci.2005;62:2283-2294.
13 Persson L,Hardemark HG,Gustafsson J,Rundstrom G,MendeI-Hartvig I,Esscher T.Pahlman S.S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum:markers of cell damage in human central nervous system.Stroke.1987;18:911-918.
14 Gao F,Harris DN,Sapsed-Byrne S.Time course of neurone-specific enolase and S-100 protein release during and after coronary artery bypass grafting,Br J Anaesth.1999;82:266-267.
15 Ingebrigtsen,T.and Romner,B.Biochemical serum markers for brain damage:A short review with emphasis on clinical utility in mild head injury.Restor Neurol Neurosci.2003;21:171-176.
16 Rosén,H.,Sunnerhagen,KS,Herlitz,J.,Blomstrand,C.and Rosengren,L.Serum levels of the brain-derived proteins S-100 and NSE predict long-term outcome after cardiac arrest.Resuscitation.200 i;49:183-191,
17 Herrmann,M.and Ehrenreich,H.Brain derived proteins as markers of acute stroke:Their relation to pathophysiology,outcome prediction and neuroprotective drug monitoring.Restor Neurol Neurosci.2003;21:177-190.
18 Gao F,Harris DN,Sapaed Byrne S,et al.Neurone-specific enolase and Sangtec 100 assays during cardiac surgery:part Ⅰ-the effects of heparin,protamine and propofol.Perfusion.1997;12:163-165.
19 Johnsson P,Backstrom M,Bergh C、et al.Increased S 100B in blood after cardiac surgery is a powerful predictor of late mortality.Ann Thorac Surg.2003;75:162-168,
20 Herrmann M.Neurobehavioral outcome prediction after cardiac surgery role of neurobiochemical markers of damage to neuronal and gilial tissure.Stroke.2000;31:645-650.
21 冀亚琦,阮新民,孙培吾,等.体外循环中S-100蛋白和神经元特异性烯醇化酶的变化及其与炎性细胞因子的关系.中国胸心血管外科临床杂志.2004;11:248-251.
22 Basile AM,Fusi C,Conti AA,et al.S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery:preliminary observation of a 6-month follow-up study.Eur Neurol.2001;45:151-159.
23 Manfred H,Anne D.Ebert,et al.Neurobehavioral outcome prediction after cardiac surgery:Role of neurobiochemical markers of damage to neuronal and glial brain tissur.Stroke.2000,31:645-650.
24,Johussou P.Markers of cerebral ischemia after cardiac surgery.J Cardiothorac Vasc Anesth.1996;10:120-126.
25 Jansen N J,van Oeveren W,van den Broek L,et al.Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass.J Thorac Cardiovasc Surg.1991;102:515-525.
26 Ashraf S,Bhattacharya K,Tian Y,et al.Cytokine and S100B levels in paediatric patients undergoing corrective cardiac surgery with or without total circulatory arrest.Eur J Cardiothorac Surg.1999;16:32-37.
27 McKeating EG,Andrews PJ,Mascia L..Relationship of neuron specific enolase and protein S-100 concentrations in systemic and jugular venous serum to injury severity and outcome after traumatic brain injury.Acta Neurochir Suppl(Wien).1998;71:117-119.
28 Colarow L,Turini M,Teneberg S,Berger A.Characterization and biological activity of gangliosides in buffalo milk.Biochim Biophys Acta.2003;1631:94-106.
29 Yang HC,Farooqui AA,Horrocks LA.Effects of glycosaminoglycans and glycosphingolipids on cytosolic phospholipases A2 from bovine brain.Biochem J.1994;299:91-95.
30 Basavarajappa BS,Saito M,Cooper TB,Hungund BL.Activation of arachidonic acidYspecific phospholipase A2 in human neuroblastoma cells after chronic alcohol exposure:prevention by GM1 ganglioside.Alcohol Clin Exp Res.1997;21:1199-1203.
31 Fukushima T,Serrero G.Characterization of calcium-independent cytosolic phospholipase A2activity in the submucosal regions of rat stomach and small intestine.Lipids.1994;29:163-169.
32 Ziegler-Heitbrock HW,Kafferlein E,Haas JG,Meyer N,Strobel M,Weber C,Flieger D:Gangliosides suppress tumor necrosis factor production in human monocytes.J Immunol.1992;148:1753-1758.
33 Park EJ,Suh M,Thomson B,et al.Dietary ganglioside inhibits acute inflammatory signals in intestinal mucosa and blood induced by systemic inflammation of Escherichia coli lipopolysaccharide.Shock..2007;28:112-117.
34 Van Eldik,L.J.,Wainwright,M.S.The Janus face of glial-derived S100B:beneficial and detrimental functions in the brain.Restor.Neurol.Neurosci.2003;21:97-108.
35 邹定全,常业恬,周建美,等.乌司他丁对心脏瓣膜置换术病人脑损伤的影响.中华麻醉学杂志.2005;25:497-500.
36 Harmon DC,Ghori KG,Eustace NP,et al.Aprotinin decreases the incidence of cognitive deficit following CABG and cardiopulmonary bypass:a pilot randomized controlled study.Can J Anaesth.2004;51:1002-1009.
37 Singh S,Hutton P.Cerebral effect s of cardiopulmonary bypass in adults.BJA-CEPD Reviews.2003;3:115-119.
38 王月兰,邵伟,邴来英,等.体外循环期间尼莫地平对脑糖代谢的影响.中华麻醉学杂忠.1999;119:596-598.
39 李景文,龙村,袁泉,等.婴幼儿围心脏手术期血乳酸浓度的变化与预后.中国体外循环杂志.2007;5:1-3.
40 Phillis JW,O'ReganMH.GMI ganglioside inhibits ischemic release of amino acid neurotransm itters from rat cortex.Neuroreport.1995;6:2010-2012.
41 胡志兵,陆雪芬,郑德枢,等.新生大鼠缺血缺氧后胶质性谷氮酸转运体的表达及GM1的干预研究.实用心脑肺血管病杂志.2006;14:774-776.
42 Liu JR,Ding MP,Wei EQ,et al.Monosialoganglioside prevented ischemic rat hippocampal slices through stabilizing expression of N-methyl-D-aspartate receptor subunit.Acta Pharmacol Sin.2004;25:727-732.
43 Avrova NF,Shestak KI,Zakharova IO,et al.The use of antioxidants to prevent glutamate-induced derangement of calcium ion metabolism in rat cerebral cortex synaptosomes.Neurosci Behav Physiol.2000;30:535-541.
44 Brock MV,Blue ME,Lowenstein CJ,et al.Induction of neuronal nitric oxide following hypothermic circulatory arrest.Ann Thorac Surg.1996;62:1313-1320.
45 刘华,濮海平,郭萍,等.新生鼠缺血再灌注脑损伤神经节苷脂的保护作用.新生儿科杂志.2004;19:261-263.
46 施建生,姜振林,秦建兵,等.神经节苷脂对不完全性脑缺血后海马CA1区NOS阳性神经元表达的影响.中国神经科学杂志.2003;19:83-87.
47 Xu Y,Kitada M,Yamaguchi M,et al.Increase in bFGF-responsive neural progenitor population following contusion injury of the adult rodent spinal cord.Neurosci Lett.2006;397:174-179.
48 Wallach CJ,Kim J S,Sobajima S,et al.Safety assessment of intradiscal gene transfer:A pilot study.Spine J.2006;6:107-112.
49 Zhou SH,Lechpammert S,Greenberger J S,et al.Hypoxia inhibition of adipocytogenesis in human bone marrow stromal cells requires transforming growth factor-β/Smad3 signaling.J Biol Chem.2005;280:22688-22696.
50 Rabin S J,BachisA,Mocchetti 1.Gangliosides activate Trk receptors by inducing the release of neurotrophins.J Biol Chem.2002;277:49466-49472.
51 Duchemin AM,Neff NH,Hadjiconstantinou M.GM1 increase the content and mRNA NGF in the brain of aged rats.Neuroreport.1997;8:3823-3827.
52 刘莉,杨国成,刘少平,等.NGF和神经节苷脂GM1对2,5-己二酮中毒性PC12细胞的协同保护作用.中国临床约理学与治疗学.2006;11:173-177.
53 Bachis A,Rabin SJ,Del Fiacco M,et al.Gangliosides prevent excitotoxity through activation of TrkB receptor.Neurotox Res.2002;4:225-234.
1 Guy M,McKhann,Maura A,et al.Stroke and encephalopathy after cardiac surgery:an update.Stroke.2006;37:562-571.
2 Mahanna EP,Blumenthal JA,White WD,et al.Defining neuropsychological dysfunction after coronary artery bypass grafting.Ann Thorac Surg.1996;61:1342-1347.
3 毕齐,张茁,贺建华,等.心脏手术后早期脑血管病并发症的临床研究.中华医学杂志.1999:79:439-440.
4 皋源,张挺杰,王祥瑞,等.体外循环心脏手术后精神障碍发生率及相关因素.上海第二医科大学学报.2004:24:916-918.
5 Eagle KA,Guyton RA,Davidoff R,et al.ACC/AHA guidelines for coronary artery bypass graft surgery:a report of the American College of Cardiology/American Heart Association task force on practice guidelines(Committee to revise the 1991 guidelines for coronary artery bypass graft surgery).J Am Coil Cardiol.1999;34:1262-347.
6 McKhann GM,Goldsborough MA,Borowicz LM,et al.Predictors of stroke risk in coronary artery bypass patients.Ann Thorac Surg.1997;63:516-521.
7 Redmond JM,Greene PS,Goldsborough MA,et al.Neurologic injury in cardiac surgical patients with a history of stroke.Ann Thorac Surg.1996;61:42-47.
8 Stolz E,Gerriets T,Kluge A,et al.Diffusion-weighted magnetic resonance imaging and neurobiochemical markers after aortic valve replacement:implications for future neuroprotective trials? Stroke.2004;35:888-892.
9 Almassi GH,Sommers T,Moritz TE,et al.Stroke in cardiac surgical patients:determinants and outcome.Ann Thorac Surg.1999;68:391-398.
10 Hogue CW,Barzilai B,Pieper KS,et al.Sex differences in neurological outcomes and mortality after cardiac surgery.Circulation.2001;103:2133-2137.
11 Knipp SC,Matatko N,Wilhelm H,et al.Evaluation of brain injury after coronary artery bypass grafting:a prospective study using neuropsychological assessment and diffusion weighted magnetic resonance imaging.Eur J Cardiothorac Surg.2004;25:791-800.
12 Bendszus M,Reents W,Franke D,et al.Brain damage after coronary artery bypass grafting.Arch Neurol.2002;59:1090-1095.
13 Restrepo L, Wityk RJ, Grega MA. et al. Diffusion- and perfusion-weighted magnetic resonance imaging of the brain before and after coronary artery bypass grafting surgery.Stroke.2002;33:2909-2915.
14 Kornfeld DS, Heller SS, Frank KA, Edie RN, Barsa J. Delirium after coronary artery bypass surgery. J Thorac Cardiovasc Surg. 1978;76:93-96.
15 McKhann GM, Grega MA, Borowicz LM, et al. Encephalopathy and stroke after coronary artery bypass grafting. Arch Neurol. 2002;59:1422-1428.
16 Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgery. N Engl J Med. 1996;335:1857-1863.
17 Newman MF, Croughwell ND, Blumenthal JA, et al. Predictors of cognitive decline after cardiac arrest. Ann Thorac Surg. 1995;59:1326-1330.
18 Pugsley W, Klinger L, Paschalis C, et al. The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke . 1994;25:1393-1399.
19 Fearn SJ. Pole R. Wesnes K, et al. Cerebral injury during cardiopulmonary bypass: emboli impair memory. J Thorac Cardiovasc Surg.2001; 121:1150-1160.
20 Sotaniemi KA, Mononen H, Hokkanen TE. Long-term cerebral outcome after open-heart surgery: a five-year neuropsychological follow-up study. Stroke. 1986; 17:410-416.
21 Newman MF, Kirchner JL, Phillips-Bute B, et al. Longitudinal assessment of neurocognitive function after coronary artery bypass surgery. N Engl J Med.2001 ;344:395-402.
22 Seines OA. Grega MA, Borowicz LM, et al. Cognitive outcomes three years after coronary artery bypass surgery: a comparison of on-pump coronary artery bypass graft surgery and nonsurgical controls. Ann Thorac Surg.2005;79:1201-1209.
23 Seines OA, McKhann GM. Neurocognitive complications after coronary artery bypass surgery.Ann Neurol.2005;57:615-621.
24 Gold JP, Charlson ME, Williams-Russo P, et al. Improvement of outcomes after coronary artery bypass. A randomized trial comparing intraoperative high versus low mean arterial pressure. J Thorac Cardiovasc Surg.1995; 110:1302-11.
25 Hartman GS, Yao FS, Bruefach M, 3rd, et al. Severity of aortic atheromatous disease diagnosed by transesophageal echocardiography predicts stroke and other outcomes associated with coronary artery surgery: a prospective study. Anesth Analg.1996;83: 701-08.
26 Lazar HL, Menzoian JO. Coronary artery bypass grafting in patients with cerebrovascular disease. Ann Thorac Surg.1998;66:968-974.
27 Tufo HM, Oltfeld AM, Shekelle R. Central nervous system dysfunction following open-heart surgery. JAMA. 1970;212:1333-1340.
28 Habib RH, Zacharias A, Schwann TA, et al. Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed? J Thorac Cardiovasc Surg. 2003;125:1438-1450.
29 Caplan LR, Hennerici M. Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke. Arch Neural.1998;55:1475-82.
30 Mackensen GB, Ti LK, Phillips-Bute BG, et al. Cerebral embolization during cardiac surgery:impact of aortic atheroma burden. Br J Anaesth.2003;91:656-661.
31 Goto T, Baba T, Matsumaya K, et al. Aortic atherosclerosis and postoperative neurological dysfunction in elderly coronary surgical patients. Ann Thorac Surg .2003;75:1912-1918.
32 Kapetanakis El, Stamou SC, Dullum MKC, et al. The impact of aortic manipulation on neurologic outcomes after coronary artery bypass surgery: a risk-adjusted study. Ann Thorac Surg.2004;78:1564-1571.
33 Brown WR, Moody DM, Challa VR, Stump DA, Hammon JW. Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli. Stroke.2000;31:707-713.
34 Jones TJ, Deal DD, Vernon JC, Blackburn N, Stump DA. Does vacuum-assisted venous drainage increase gaseous microemboli during cardiopulmonary bypass? Ann Thorac Surg .2002;74:2132-2137.
35 Bar-Yosef S, Anders M, Mackensen GB, et al. Aortic atheroma burden and cognitive dysfunction after coronary artery bypass graft surgery. Neurologic Outcomes Research Group.CARE Investigators. Ann Thorac Surg.2004; 78:1556-1562.
36 Fearn SJ, Pole R, Wesnes K, et al. Cerebral injury during cardiopulmonary bypass: emboli impair memory. J Thorac Cardiovasc Surg.2001; 121:1150-1160
37 Moody DM, Brown WR, Challa VR, et al. Brain microemboli associated with cardiopulmonary bypass: a histologic and magnetic resonance imaging study. Ann Thorac Surg.l995;59:1304-1307.
38 Friday G, Sutter F, Curtin A, et al. Brain magnetic resonance imaging abnormalities followingo. -pump cardiac surgery. Heart Surg Forum.2005; 8: E105-109.
39 Almassi GH, Sommers T, Moritz TE, et al. Stroke in cardiac surgical patients: determinants and outcome. Ann Thorac Surg.1999;68:391-398.
40 D'Agostino RS, Svensson LG, Neumann DJ, et al. Screening carotid ultrasonography and risk factors for stroke in coronary artery surgery patients. Ann Thorac Surg. 1996;62:1714-1723.
41 Yoon BW, Bae HJ, Kang DW, et al. Intracranial cerebral artery disease as a risk factor for central nervous system complications of coronary artery bypass graft surgery.Stroke.2001;32:94-99.
42 Westaby S, Saatvedt K, White S, et al. Is there a relationship between cognitive dysfunction and systemic inflammatory response after cardiopulmonary bypass? Ann Thorac Surg.2001;71:667-672.
43 Mathew JP, Shernan SK, White WD. Preliminary report of the effects of complement suppression with pexelizumab on neurocognitive decline after coronary artery bypass graft surgery. Stroke.2004;35:2335-39.
44 Mathew JP, Grocott HP, Phillips-Bute B, et al. Lower endotoxin immunity predicts increased cognitive dysfunction in elderly patients after cardiac surgery. Stroke.2003;34:508-513.
45 Jansen NJ, van Oeveren W, van den Broek L, et al. Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1991;102:515-525.
46 Ohata T, Sawa Y, Kadoba K, et al. Normothermia has beneficial effects in cardiopulmonary bypass attenuating inflammatory reactions. ASAIO J.1995; 41 :M288-M291.
47 McMahon SB, Cafferty WB, Marchand F. Immune and glial cell factors as pain mediators and modulators. Exp Neurol.2005; 192:444-462.
48 Matsumura K, Kobayashi S. Signaling the brain in inflammation: the role of endothelial cells.Front Biosci.2004;9:2819-2826.
49 Giovannini MG, Scali C, Prosperi C, et al. Experimental brain inflammation and neurodegeneration as model of Alzheimer's disease: protective effects of selective COX-2 inhibitors. Int J Immunopathol Pharmacol.2003;16(suppl):31-40.
50 Sparks DL, Gross DR, Hunsaker JC. Neuropathology of mitral valve prolapse in man and cardiopulmonary bypass (CPB) surgery in adolescent Yorkshire pigs. Neurobiol Aging.2000;21:363-372.
51 Seines OA, Goldsborough MA, Borowicz LM Jr. et al. Determinants of cognitive change after coronary artery bypass surgery: a multifactorial problem. Ann Thorac Surg.1999;67:1669-1676.
52 Yao Y, Chinnici C, Tang H, et al. Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimerlike brain amyloidosis. J Neuroinflammation .2004; 1:21.
53 Cacquevel M, Lebeurrier N, Cheenne S, et al. Cytokines in neuroinflammation and Alzheimer's disease. Curr Drug Targets.2004;5:529-534.
54 Kushi H, Saito T, Makino K, et al. IL-8 is a key mediator of neuroinflammation in severe traumatic brain injuries. Acta Neurochir Suppl.2003;86:347-350.
55 Edwardson J, Morris C. The genetics of Alzheimer's disease. BMJ.1998;317:361-362.
56 Tardiff BE, Newman MF, Saunders AM et al. Preliminary report of a genetic basis for cognitive decline after cardiac operations. Ann Thorac Surg.1997;64:715-720.
57 Newman MF, Mathew JP,Grocott HP,et,al.Central nervous system injury associated with cardiac surgery. Lancet.2006;368:694-703.
58 Myles PS,Cairo S.Artifact in the bispectral index in a patient with severe ischemic brain injury.Anesth Analg.2004;98:706-707.
59 Lundell JC, Scuderi PE, Butterworth JF. Less isoflurane is required after than before cardiopulmonary bypass to maintain a constant bispectral index value. J Cardiothorac Vasc Anesth. 2001;15:551-554.
60 Honan D, Doherty D, Frizelle H. A comparison of the effects on bispectral index of mild vs.moderate hypothermia during cardiopulmonary bypass. Eur J Anaesthesiol. 2006; 14:1-6.
61 Austin EH 3rd,Edmonds HL Jr,Auden SM,et al. Benefit of neurophysiologic monitoring for pediatric cardiac surgery. J Thorac Cardiovasc Surg. 1997;114:707-715.
62 Schell RM, Kern FH, Reves JGThe role of continuous jugular venous saturation monitoring during cardiac surgery with cardiopulmonary bypass. Anesth Analg. l992;74:627-629.
63 Schell RM, Cole DJ. Cerebral monitoring: jugular venous oximetry.Anesth Analg. 2000 90:559-566.
64 Sakamoto T, Zurakowski D. Interaction of temperature with hematocrit level and pH determines safe duration of hypothermic circulatory arrest.. J Thorac Cardiovasc Surg.2004;128:220-232.
65 Morimoto Y, Niida Y. Changes in cerebral oxygenation in children undergoing surgical repair of ventricular septal defects. Anaesthesia.2003;58:77-83.
66 Shaaban AM, Harmer M. A pilot study of evaluation of cerebral function by S100beta protein and near-infrared spectroscope during cold and warm cardiopulmonarybypass in infants and children undergoing open-heart surgery. Anaesthesia .2004;59:20-26.
67 Andropoulos DB, Stayer SA. Neurological monitoring for congenital heart surgery. Anesth Analg.2004;99:1365-1375.
68 Diegeler A, Hirsch R, Schneider F, Schilling LO, Falk V, Rauch T, Mohr FW.Neuromonitoring and neurocognitive outcome in off pump versus conventional coronary bypass operation.Ann T'horac Surg. 2000;69:1162-1166.
69 Persson L, Hardemark HG Gustafsson J, Rundstrom G, Mendel-Hartvig I, Esscher T, Pahlman S.S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system. Stroke. 1987; 18:911-918.
70 Gao F, Harris DN, Sapsed-Byrne S. Time course of neurone-specific enolase and S-100 protein release during and after coronary artery bypass grafting. Br J Anaesth.l999;82:266-267.
71 Johnsson P, Backstrom M, Bergh C, et al.Increased S 100B in blood after cardiac surgery is a powerful predictor of late mortality. Ann Thorac Surg. 2003;75:162-168.
72 Basile AM, Fusi C, Conti AA, et al. S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery: preliminary observation of a 6-month follow-up study.Eur Neurol. 2001;45:151-159.
73 Nakamura K, Ueno T, Yamamoto H, et al.Relationship between cerebral injury and inflammatory responses in patients undergoing cardiac surgery with cardiopulmonary bypass. Cytokine. 2005;29:95-104.
74 Svenmarker SEngstrom KG Karlsson T, et al.Influence of pericardia! suction blood retransfusion on memory function and release of protein S100B. Perfusion. 2004; 19:337-343.
75 Fazio V, Bhudia SK, Marchi N, Aumayr B, Janigro D. Peripheral detection of S100beta during cardiothoracic surgery: what are we really measuring?Ann Thorac Surg.2004;78:46-52;discussion 52-3.
76 Nathan HJ, Wells GA, Munson JL, Wozny D. Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass. Circulation.2001;104(Suppl. 1):85-91.
77 Grigore AM, Grocott HP, Mathew J et al. The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery. Anesth Analg.2002; 94: 4-10.
78 Busto R, Globus MY, Dietrich WD, Martinez E, Valdes I, Ginsberg MD. Effect of mild hypothermia on ischemiainduced release of neurotransmitters and free fatty acids in rat brain.Stroke. 1989; 20: 904-910.
79 Jones TJ, Stump DA, Deal DD, Vemon JC, Manuel JC. Hypothermia protects the brain from embolization by reducing and redirecting the embolic load. Ann Thorac Surg.l999;68:1465.
80 Grocott HP, Mackensen B, Grigore AM et al. Postoperative hyperthermia is associated with cognitive dysfunction after coronary artery bypass graft surgery. Stroke.2002;33:537-41.
81 Barbut D, Grassineau D, Lis E, et al. Posterior distribution of infarcts in strokes related to cardiac operations. Ann Thorac Surg.1998;65:1656-1659.
82 Sadahiro M, Haneda K, Mohri H. Experimental study of cerebral autoregulation during cardiopulmonary bypass with or without pulsatile perfusion. J Thorac Cardiovasc Surg.1994; 108:446-454.
83 Murkin JM, Martzke JS, Buchan AM, et al. A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery. I. Mortality and cardiovascular morbidity. II. Neurologic and cognitive outcome J Thorac Cardiovasc Surg.1995; 110:340-62.
84 Kirklin JW, Barrat-Boyes BG. Hypothermia, circulatory arrest, and cardiopulmonary bypass.In: Cardiac surgery. New York: Churchill Livingstone. 1993:62-73.
85 Mathew J, Grocott H, Phillips-Bute B, et al. Extreme hemodilution is associated with increased cognitive dysfunction in the elderly after cardiac surgery. Anesth Analg.2004;98:SCA21.
86 Jonas RA, Wypij D, Roth SJ, et al. The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants. J Thorac Cardiovasc Surg.2003; 126:1765-1774.
87 Bathein G, Townes B.A randomized trial of carbon dioxide management during hypothermic cardiopulmonary bypass. Anesthesiology.l990;72:7-15.
88 Stephan H, Weyland A.Acid-base management during hypothermic cardiopulmonary bypass does not affect cerebral metabolism but dose affect blood flow and neurological outcome. Br J Anaesth.l992;69:51-57.
89 du Plessis AJ, Jonas RA, Wypij D, et al. Perioperative effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg.1997;114:991-1001.
90 Aoki M, Nomura F. Effects of pH on brain energetics after hypothermic circulatory arrest.Ann Thorac Surg.1993;55:1093-1103.
91 Bellinger DC, Wypij D, du Plessis AJ, et al. Developmental and neurologic effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg.2001; 121:374-383.
92 De Ferranti S, Gauvreau K, Kickey PR, et al. Intraoperative hyperglycemia during infant cardiac surgery is not associated with adverse neurodevelopmental outcomes at 1,4, and 8 years. Anesthesiology.2004; 100:1339-1341.
93 Butterworth J, Wagenknecht LE, Legault C, et al. Attempted control of hyperglycemia during cardiopulmonary bypass fails to improve neurologic or neurobehavioral outcomes in patients without diabetes mellitus undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg.2005; 130:1319-1325.
94 Gaynor JW, Nicolson SC. Increasing duration of deep hypothermic circulatory arrest is associated with an increased incidence of postoperative electroencephalographic seizures. J Thorac Cardiovasc surg.2005; 130:1278-1286.
95 Williams GD.Ramamoorthy C. Brain monitoring and protection during pediatric cardiac surgery. Semin Cardiothorac Vasc Anesth. 2007; 11:23-33.
96 Reichenspurner H, Navia JA, Berry G et al. Paniculate emboli capture by an intra-aortic filter device during cardiac surgery. J Thorac Cardiovasc Surg.2000;119:233-241.
97 Bergman P,Hadjinikolaou L, van der Linden J.Aortic atheroma is related to number of particulates captured by intra-aortic filtration in CABG. Eur J Cardiothorac Surg.2002;22:539-544.
98 White BC, Sullivan JM, DeGarcia DJ, et al. Brain ischemia and reperfusion: molecular mechanism of neuronal injury. J Neurol Sci.2000; 179:1 -33.
99 Brock MV, Blue ME, Lowenstein CJ, et al. Induction of neuronal nitric oxide following hypothermic circulatory arrest. Ann Thorac Surg. 1996;62:1313-1320.
100 Nussmeier NA, Arlund C, Slogoff S. Neuropsychiatric complications after cardiopulmonary bypass: cerebral protection by a barbiturate. Anesthesiolgy.1986;64:165-170.
101 Zaidan JR, Klochany A, Martin WM, et al. Effect of thiopental on neurologic outcome following coronary artery bypass grafting. Anesthesiology. 1991 ;74:406-411.
102 Roach GW, Newman MF, Murkin JM, et al., for the Multicenter Study of Perioperative Ischemia (McSPI) Research Group. Ineffectiveness of burst suppression therapy in mitigating perioperative cerebrovascular dysfunction. Anesthesiology.1999;90:1255-1264.
103 Hindman BJ, Todd MM. Improving neurologic outcome after cardiac surgery.Anesthesiology. 1999;90:1243-1247.
104 Arrowsmith JE, Harrison MJ, Newman SP, et al. Neuroprotection of the brain during cardiopulmonary bypass: a randomized trial of remacemide during cardiopulmonary bypass.Stroke.1998;29:2357-2362.
105 Mitchell SJ, Pellet O, Gorman DF. Cerebral protection by lidocaine during cardiac operations.Ann Thorac Surg.1999;67:1117-1124.
106 Wang D, Wu X, Li J, et al. The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery. Anesth Analg.2002;95:1134-1141.
107 Mathew JP, Shernan SK, White WD, et al. Preliminary report of the effects of complement suppression with pexelizumab on neurocognitive decline after coronary artery bypass graft surgery. Stroke.2004;35:2335-2339.
108 Levy J, Pifarre R, Schaff H, et al. A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood los and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting. Circulation. 1995;92:2236-2244.
109 Harmon DC, Ghori KG, Eustace NP, et al. Aprotinin decreases the incidence of cognitive deficit following CABG and cardiopulmonary bypass: a pilot randomized controlled study.Can J Anaesth.2004;51:1002-1009.
110 Ferguson TB, Coombs LP, Peterson ED. Preoperative beta-blocker use and mortality and morbidity following CABG surgery in North America. JAMA.2002;287:2221-2227.
111 Amory DW, Grigore A, Amory JK et al. Neuroprotection is associated with beta-adrenergic receptor antagonists during cardiac surgery: evidence from 2575 patients. J Cardiothorac Vasc Anesth.2002;16:270-277.
112 Mocchetti I. Exogenous gangliosides,neuronal plasticity and repair, and the neurotrophins.Cell Mol Life Sci.2005;62:2283-2294.
113 Alter M. GM1 ganglioside for acute ischemic stroke: trial design issues. Ann N Y Acad Sci. 1998;845:391 -401.
114 Geisler FH. Clinical trials of pharmacotherapy for spinal cord injury. Ann N Y Acad Sci.1998;845:374-381.
115 Giacinto G, Marilyn H, Alfred T, et al. Evaluating neuroprotective agents for clinical antiischemic benefit using neuropsychological changes after cardiac surgery under cardiopulmonary bypass Methodological strategies and results of a double-blind,placebo-controlled trial of GM1 ganglioside. Stroke.1996;27:858-874.
116 Redmond JM, Gillinov AM, Blue ME,et,al. The monosialoganglioside, GM1, reduces neurologic injury associated with hypothermic circulatory arrest. Surgery. 1993; 114:324-332.
117 Phillis JW, O'ReganMH. GM1 ganglioside inhibits ischemic release of amino acid neurotransmitters from rat cortex. Neuroreport.1995;6:2010-2012.
118 Liu JR ,Ding MP ,Wei EQ , et al. Monosialoganglioside prevented ischemic rat hippocampal slices through stabilizing expression of N - methyl - D - aspartate receptor subunit . Acta Pharmacol Sin.2004;25:727-732.
119 Avrova NF, Shestak KI, Zakharova 10, et al. The use of antioxidants to prevent glutamate-induced derangement of calcium ion metabolism in rat cerebral cortex synaptosomes. Neurosci Behav Physiol.2000;30:535-541.
120 Tseng EE ,Brock MV ,Lange MS , et al . Monosialoganglioside GM1 inhibits neurotoxicity after hypothermic circulatory arrest. Surgery. 1998; 124:298-306.
121 Rabin SJ, BachisA, Mocchetti I. Gangliosides activate Trk receptors by inducing the release of neurotrophins. J Biol Chem.2002;277: 49466-49472.
2 Mahanna EP,Blumenthal JA,White WD,et al.Defining neuropsychological dysfunction after coronary artery bypass grafting.Ann Thorac Surg.1996;61:1342-1347.
3 毕齐,张出,贺建华,等.心脏手术后早期脑血管病并发症的临床研究.中华医学杂志.1999:79:439-440.
4 皋源,张挺杰,王祥瑞,等.体外循环心脏手术后精神障碍发生率及相关因素.上海第二医科大学学报.2004:24:916-918.
5 Mocchetti I,et al.Exogenous gangliosides,neuronal plasticity and repair,and the neurotrophins.Cell Mol Life Sci.2005;62:2283o2294.
6 Alter M,et al.GM1 ganglioside for acute ischemic stroke:trial design issues.Ann N Y Acad Sci,1998;845:391-401.
7 Geisler FH,et al.Clinical trials of pharmacotherap,v for spinal cord injury.Ann N Y Acad Sci,1998;845:374-381.
8 Leon A,Lipartiti M,Seren MS,et al.Hypoxic-ischemic damage and the neuroprotective effects of GMlganglioside.Stroke.1990;21(11 Suppl):Ⅲ95-97.
9 Giacinto G,Marilyn H,Alfred T,et al.Evaluating neuroprotective agents for clinical antiischemic benefit using neuropsychological changes after cardiac surgery under cardiopulmonary bypass Methodological strategies and results of a double-blind,placebo-controlled trial of GMl ganglioside.Stroke.1996;27:858-874.
10 Redmond JM,Gillinov AM,Blue ME,et,al.The monosialoganglioside,GM1,reduces neurologic injury associated with hypothermic circulatory arrest.Surgery.1993;114:324-332.
11 Tseng EE,Brock MV,Lange MS,et al.Monosialoganglioside GM1 inhibits neurotoxicity after hypothermic circulatory arrest.Surgery.1998;124:298-306.
12 Mocchetti I.Exogenous gangliosides,neuronal plasticity and repair,and the neurotrophins.Mol Life Sci.2005;62:2283-2294.
13 Persson L,Hardemark HG,Gustafsson J,Rundstrom G,MendeI-Hartvig I,Esscher T.Pahlman S.S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum:markers of cell damage in human central nervous system.Stroke.1987;18:911-918.
14 Gao F,Harris DN,Sapsed-Byrne S.Time course of neurone-specific enolase and S-100 protein release during and after coronary artery bypass grafting,Br J Anaesth.1999;82:266-267.
15 Ingebrigtsen,T.and Romner,B.Biochemical serum markers for brain damage:A short review with emphasis on clinical utility in mild head injury.Restor Neurol Neurosci.2003;21:171-176.
16 Rosén,H.,Sunnerhagen,KS,Herlitz,J.,Blomstrand,C.and Rosengren,L.Serum levels of the brain-derived proteins S-100 and NSE predict long-term outcome after cardiac arrest.Resuscitation.200 i;49:183-191,
17 Herrmann,M.and Ehrenreich,H.Brain derived proteins as markers of acute stroke:Their relation to pathophysiology,outcome prediction and neuroprotective drug monitoring.Restor Neurol Neurosci.2003;21:177-190.
18 Gao F,Harris DN,Sapaed Byrne S,et al.Neurone-specific enolase and Sangtec 100 assays during cardiac surgery:part Ⅰ-the effects of heparin,protamine and propofol.Perfusion.1997;12:163-165.
19 Johnsson P,Backstrom M,Bergh C、et al.Increased S 100B in blood after cardiac surgery is a powerful predictor of late mortality.Ann Thorac Surg.2003;75:162-168,
20 Herrmann M.Neurobehavioral outcome prediction after cardiac surgery role of neurobiochemical markers of damage to neuronal and gilial tissure.Stroke.2000;31:645-650.
21 冀亚琦,阮新民,孙培吾,等.体外循环中S-100蛋白和神经元特异性烯醇化酶的变化及其与炎性细胞因子的关系.中国胸心血管外科临床杂志.2004;11:248-251.
22 Basile AM,Fusi C,Conti AA,et al.S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery:preliminary observation of a 6-month follow-up study.Eur Neurol.2001;45:151-159.
23 Manfred H,Anne D.Ebert,et al.Neurobehavioral outcome prediction after cardiac surgery:Role of neurobiochemical markers of damage to neuronal and glial brain tissur.Stroke.2000,31:645-650.
24,Johussou P.Markers of cerebral ischemia after cardiac surgery.J Cardiothorac Vasc Anesth.1996;10:120-126.
25 Jansen N J,van Oeveren W,van den Broek L,et al.Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass.J Thorac Cardiovasc Surg.1991;102:515-525.
26 Ashraf S,Bhattacharya K,Tian Y,et al.Cytokine and S100B levels in paediatric patients undergoing corrective cardiac surgery with or without total circulatory arrest.Eur J Cardiothorac Surg.1999;16:32-37.
27 McKeating EG,Andrews PJ,Mascia L..Relationship of neuron specific enolase and protein S-100 concentrations in systemic and jugular venous serum to injury severity and outcome after traumatic brain injury.Acta Neurochir Suppl(Wien).1998;71:117-119.
28 Colarow L,Turini M,Teneberg S,Berger A.Characterization and biological activity of gangliosides in buffalo milk.Biochim Biophys Acta.2003;1631:94-106.
29 Yang HC,Farooqui AA,Horrocks LA.Effects of glycosaminoglycans and glycosphingolipids on cytosolic phospholipases A2 from bovine brain.Biochem J.1994;299:91-95.
30 Basavarajappa BS,Saito M,Cooper TB,Hungund BL.Activation of arachidonic acidYspecific phospholipase A2 in human neuroblastoma cells after chronic alcohol exposure:prevention by GM1 ganglioside.Alcohol Clin Exp Res.1997;21:1199-1203.
31 Fukushima T,Serrero G.Characterization of calcium-independent cytosolic phospholipase A2activity in the submucosal regions of rat stomach and small intestine.Lipids.1994;29:163-169.
32 Ziegler-Heitbrock HW,Kafferlein E,Haas JG,Meyer N,Strobel M,Weber C,Flieger D:Gangliosides suppress tumor necrosis factor production in human monocytes.J Immunol.1992;148:1753-1758.
33 Park EJ,Suh M,Thomson B,et al.Dietary ganglioside inhibits acute inflammatory signals in intestinal mucosa and blood induced by systemic inflammation of Escherichia coli lipopolysaccharide.Shock..2007;28:112-117.
34 Van Eldik,L.J.,Wainwright,M.S.The Janus face of glial-derived S100B:beneficial and detrimental functions in the brain.Restor.Neurol.Neurosci.2003;21:97-108.
35 邹定全,常业恬,周建美,等.乌司他丁对心脏瓣膜置换术病人脑损伤的影响.中华麻醉学杂志.2005;25:497-500.
36 Harmon DC,Ghori KG,Eustace NP,et al.Aprotinin decreases the incidence of cognitive deficit following CABG and cardiopulmonary bypass:a pilot randomized controlled study.Can J Anaesth.2004;51:1002-1009.
37 Singh S,Hutton P.Cerebral effect s of cardiopulmonary bypass in adults.BJA-CEPD Reviews.2003;3:115-119.
38 王月兰,邵伟,邴来英,等.体外循环期间尼莫地平对脑糖代谢的影响.中华麻醉学杂忠.1999;119:596-598.
39 李景文,龙村,袁泉,等.婴幼儿围心脏手术期血乳酸浓度的变化与预后.中国体外循环杂志.2007;5:1-3.
40 Phillis JW,O'ReganMH.GMI ganglioside inhibits ischemic release of amino acid neurotransm itters from rat cortex.Neuroreport.1995;6:2010-2012.
41 胡志兵,陆雪芬,郑德枢,等.新生大鼠缺血缺氧后胶质性谷氮酸转运体的表达及GM1的干预研究.实用心脑肺血管病杂志.2006;14:774-776.
42 Liu JR,Ding MP,Wei EQ,et al.Monosialoganglioside prevented ischemic rat hippocampal slices through stabilizing expression of N-methyl-D-aspartate receptor subunit.Acta Pharmacol Sin.2004;25:727-732.
43 Avrova NF,Shestak KI,Zakharova IO,et al.The use of antioxidants to prevent glutamate-induced derangement of calcium ion metabolism in rat cerebral cortex synaptosomes.Neurosci Behav Physiol.2000;30:535-541.
44 Brock MV,Blue ME,Lowenstein CJ,et al.Induction of neuronal nitric oxide following hypothermic circulatory arrest.Ann Thorac Surg.1996;62:1313-1320.
45 刘华,濮海平,郭萍,等.新生鼠缺血再灌注脑损伤神经节苷脂的保护作用.新生儿科杂志.2004;19:261-263.
46 施建生,姜振林,秦建兵,等.神经节苷脂对不完全性脑缺血后海马CA1区NOS阳性神经元表达的影响.中国神经科学杂志.2003;19:83-87.
47 Xu Y,Kitada M,Yamaguchi M,et al.Increase in bFGF-responsive neural progenitor population following contusion injury of the adult rodent spinal cord.Neurosci Lett.2006;397:174-179.
48 Wallach CJ,Kim J S,Sobajima S,et al.Safety assessment of intradiscal gene transfer:A pilot study.Spine J.2006;6:107-112.
49 Zhou SH,Lechpammert S,Greenberger J S,et al.Hypoxia inhibition of adipocytogenesis in human bone marrow stromal cells requires transforming growth factor-β/Smad3 signaling.J Biol Chem.2005;280:22688-22696.
50 Rabin S J,BachisA,Mocchetti 1.Gangliosides activate Trk receptors by inducing the release of neurotrophins.J Biol Chem.2002;277:49466-49472.
51 Duchemin AM,Neff NH,Hadjiconstantinou M.GM1 increase the content and mRNA NGF in the brain of aged rats.Neuroreport.1997;8:3823-3827.
52 刘莉,杨国成,刘少平,等.NGF和神经节苷脂GM1对2,5-己二酮中毒性PC12细胞的协同保护作用.中国临床约理学与治疗学.2006;11:173-177.
53 Bachis A,Rabin SJ,Del Fiacco M,et al.Gangliosides prevent excitotoxity through activation of TrkB receptor.Neurotox Res.2002;4:225-234.
1 Guy M,McKhann,Maura A,et al.Stroke and encephalopathy after cardiac surgery:an update.Stroke.2006;37:562-571.
2 Mahanna EP,Blumenthal JA,White WD,et al.Defining neuropsychological dysfunction after coronary artery bypass grafting.Ann Thorac Surg.1996;61:1342-1347.
3 毕齐,张茁,贺建华,等.心脏手术后早期脑血管病并发症的临床研究.中华医学杂志.1999:79:439-440.
4 皋源,张挺杰,王祥瑞,等.体外循环心脏手术后精神障碍发生率及相关因素.上海第二医科大学学报.2004:24:916-918.
5 Eagle KA,Guyton RA,Davidoff R,et al.ACC/AHA guidelines for coronary artery bypass graft surgery:a report of the American College of Cardiology/American Heart Association task force on practice guidelines(Committee to revise the 1991 guidelines for coronary artery bypass graft surgery).J Am Coil Cardiol.1999;34:1262-347.
6 McKhann GM,Goldsborough MA,Borowicz LM,et al.Predictors of stroke risk in coronary artery bypass patients.Ann Thorac Surg.1997;63:516-521.
7 Redmond JM,Greene PS,Goldsborough MA,et al.Neurologic injury in cardiac surgical patients with a history of stroke.Ann Thorac Surg.1996;61:42-47.
8 Stolz E,Gerriets T,Kluge A,et al.Diffusion-weighted magnetic resonance imaging and neurobiochemical markers after aortic valve replacement:implications for future neuroprotective trials? Stroke.2004;35:888-892.
9 Almassi GH,Sommers T,Moritz TE,et al.Stroke in cardiac surgical patients:determinants and outcome.Ann Thorac Surg.1999;68:391-398.
10 Hogue CW,Barzilai B,Pieper KS,et al.Sex differences in neurological outcomes and mortality after cardiac surgery.Circulation.2001;103:2133-2137.
11 Knipp SC,Matatko N,Wilhelm H,et al.Evaluation of brain injury after coronary artery bypass grafting:a prospective study using neuropsychological assessment and diffusion weighted magnetic resonance imaging.Eur J Cardiothorac Surg.2004;25:791-800.
12 Bendszus M,Reents W,Franke D,et al.Brain damage after coronary artery bypass grafting.Arch Neurol.2002;59:1090-1095.
13 Restrepo L, Wityk RJ, Grega MA. et al. Diffusion- and perfusion-weighted magnetic resonance imaging of the brain before and after coronary artery bypass grafting surgery.Stroke.2002;33:2909-2915.
14 Kornfeld DS, Heller SS, Frank KA, Edie RN, Barsa J. Delirium after coronary artery bypass surgery. J Thorac Cardiovasc Surg. 1978;76:93-96.
15 McKhann GM, Grega MA, Borowicz LM, et al. Encephalopathy and stroke after coronary artery bypass grafting. Arch Neurol. 2002;59:1422-1428.
16 Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgery. N Engl J Med. 1996;335:1857-1863.
17 Newman MF, Croughwell ND, Blumenthal JA, et al. Predictors of cognitive decline after cardiac arrest. Ann Thorac Surg. 1995;59:1326-1330.
18 Pugsley W, Klinger L, Paschalis C, et al. The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke . 1994;25:1393-1399.
19 Fearn SJ. Pole R. Wesnes K, et al. Cerebral injury during cardiopulmonary bypass: emboli impair memory. J Thorac Cardiovasc Surg.2001; 121:1150-1160.
20 Sotaniemi KA, Mononen H, Hokkanen TE. Long-term cerebral outcome after open-heart surgery: a five-year neuropsychological follow-up study. Stroke. 1986; 17:410-416.
21 Newman MF, Kirchner JL, Phillips-Bute B, et al. Longitudinal assessment of neurocognitive function after coronary artery bypass surgery. N Engl J Med.2001 ;344:395-402.
22 Seines OA. Grega MA, Borowicz LM, et al. Cognitive outcomes three years after coronary artery bypass surgery: a comparison of on-pump coronary artery bypass graft surgery and nonsurgical controls. Ann Thorac Surg.2005;79:1201-1209.
23 Seines OA, McKhann GM. Neurocognitive complications after coronary artery bypass surgery.Ann Neurol.2005;57:615-621.
24 Gold JP, Charlson ME, Williams-Russo P, et al. Improvement of outcomes after coronary artery bypass. A randomized trial comparing intraoperative high versus low mean arterial pressure. J Thorac Cardiovasc Surg.1995; 110:1302-11.
25 Hartman GS, Yao FS, Bruefach M, 3rd, et al. Severity of aortic atheromatous disease diagnosed by transesophageal echocardiography predicts stroke and other outcomes associated with coronary artery surgery: a prospective study. Anesth Analg.1996;83: 701-08.
26 Lazar HL, Menzoian JO. Coronary artery bypass grafting in patients with cerebrovascular disease. Ann Thorac Surg.1998;66:968-974.
27 Tufo HM, Oltfeld AM, Shekelle R. Central nervous system dysfunction following open-heart surgery. JAMA. 1970;212:1333-1340.
28 Habib RH, Zacharias A, Schwann TA, et al. Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed? J Thorac Cardiovasc Surg. 2003;125:1438-1450.
29 Caplan LR, Hennerici M. Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke. Arch Neural.1998;55:1475-82.
30 Mackensen GB, Ti LK, Phillips-Bute BG, et al. Cerebral embolization during cardiac surgery:impact of aortic atheroma burden. Br J Anaesth.2003;91:656-661.
31 Goto T, Baba T, Matsumaya K, et al. Aortic atherosclerosis and postoperative neurological dysfunction in elderly coronary surgical patients. Ann Thorac Surg .2003;75:1912-1918.
32 Kapetanakis El, Stamou SC, Dullum MKC, et al. The impact of aortic manipulation on neurologic outcomes after coronary artery bypass surgery: a risk-adjusted study. Ann Thorac Surg.2004;78:1564-1571.
33 Brown WR, Moody DM, Challa VR, Stump DA, Hammon JW. Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli. Stroke.2000;31:707-713.
34 Jones TJ, Deal DD, Vernon JC, Blackburn N, Stump DA. Does vacuum-assisted venous drainage increase gaseous microemboli during cardiopulmonary bypass? Ann Thorac Surg .2002;74:2132-2137.
35 Bar-Yosef S, Anders M, Mackensen GB, et al. Aortic atheroma burden and cognitive dysfunction after coronary artery bypass graft surgery. Neurologic Outcomes Research Group.CARE Investigators. Ann Thorac Surg.2004; 78:1556-1562.
36 Fearn SJ, Pole R, Wesnes K, et al. Cerebral injury during cardiopulmonary bypass: emboli impair memory. J Thorac Cardiovasc Surg.2001; 121:1150-1160
37 Moody DM, Brown WR, Challa VR, et al. Brain microemboli associated with cardiopulmonary bypass: a histologic and magnetic resonance imaging study. Ann Thorac Surg.l995;59:1304-1307.
38 Friday G, Sutter F, Curtin A, et al. Brain magnetic resonance imaging abnormalities followingo. -pump cardiac surgery. Heart Surg Forum.2005; 8: E105-109.
39 Almassi GH, Sommers T, Moritz TE, et al. Stroke in cardiac surgical patients: determinants and outcome. Ann Thorac Surg.1999;68:391-398.
40 D'Agostino RS, Svensson LG, Neumann DJ, et al. Screening carotid ultrasonography and risk factors for stroke in coronary artery surgery patients. Ann Thorac Surg. 1996;62:1714-1723.
41 Yoon BW, Bae HJ, Kang DW, et al. Intracranial cerebral artery disease as a risk factor for central nervous system complications of coronary artery bypass graft surgery.Stroke.2001;32:94-99.
42 Westaby S, Saatvedt K, White S, et al. Is there a relationship between cognitive dysfunction and systemic inflammatory response after cardiopulmonary bypass? Ann Thorac Surg.2001;71:667-672.
43 Mathew JP, Shernan SK, White WD. Preliminary report of the effects of complement suppression with pexelizumab on neurocognitive decline after coronary artery bypass graft surgery. Stroke.2004;35:2335-39.
44 Mathew JP, Grocott HP, Phillips-Bute B, et al. Lower endotoxin immunity predicts increased cognitive dysfunction in elderly patients after cardiac surgery. Stroke.2003;34:508-513.
45 Jansen NJ, van Oeveren W, van den Broek L, et al. Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1991;102:515-525.
46 Ohata T, Sawa Y, Kadoba K, et al. Normothermia has beneficial effects in cardiopulmonary bypass attenuating inflammatory reactions. ASAIO J.1995; 41 :M288-M291.
47 McMahon SB, Cafferty WB, Marchand F. Immune and glial cell factors as pain mediators and modulators. Exp Neurol.2005; 192:444-462.
48 Matsumura K, Kobayashi S. Signaling the brain in inflammation: the role of endothelial cells.Front Biosci.2004;9:2819-2826.
49 Giovannini MG, Scali C, Prosperi C, et al. Experimental brain inflammation and neurodegeneration as model of Alzheimer's disease: protective effects of selective COX-2 inhibitors. Int J Immunopathol Pharmacol.2003;16(suppl):31-40.
50 Sparks DL, Gross DR, Hunsaker JC. Neuropathology of mitral valve prolapse in man and cardiopulmonary bypass (CPB) surgery in adolescent Yorkshire pigs. Neurobiol Aging.2000;21:363-372.
51 Seines OA, Goldsborough MA, Borowicz LM Jr. et al. Determinants of cognitive change after coronary artery bypass surgery: a multifactorial problem. Ann Thorac Surg.1999;67:1669-1676.
52 Yao Y, Chinnici C, Tang H, et al. Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimerlike brain amyloidosis. J Neuroinflammation .2004; 1:21.
53 Cacquevel M, Lebeurrier N, Cheenne S, et al. Cytokines in neuroinflammation and Alzheimer's disease. Curr Drug Targets.2004;5:529-534.
54 Kushi H, Saito T, Makino K, et al. IL-8 is a key mediator of neuroinflammation in severe traumatic brain injuries. Acta Neurochir Suppl.2003;86:347-350.
55 Edwardson J, Morris C. The genetics of Alzheimer's disease. BMJ.1998;317:361-362.
56 Tardiff BE, Newman MF, Saunders AM et al. Preliminary report of a genetic basis for cognitive decline after cardiac operations. Ann Thorac Surg.1997;64:715-720.
57 Newman MF, Mathew JP,Grocott HP,et,al.Central nervous system injury associated with cardiac surgery. Lancet.2006;368:694-703.
58 Myles PS,Cairo S.Artifact in the bispectral index in a patient with severe ischemic brain injury.Anesth Analg.2004;98:706-707.
59 Lundell JC, Scuderi PE, Butterworth JF. Less isoflurane is required after than before cardiopulmonary bypass to maintain a constant bispectral index value. J Cardiothorac Vasc Anesth. 2001;15:551-554.
60 Honan D, Doherty D, Frizelle H. A comparison of the effects on bispectral index of mild vs.moderate hypothermia during cardiopulmonary bypass. Eur J Anaesthesiol. 2006; 14:1-6.
61 Austin EH 3rd,Edmonds HL Jr,Auden SM,et al. Benefit of neurophysiologic monitoring for pediatric cardiac surgery. J Thorac Cardiovasc Surg. 1997;114:707-715.
62 Schell RM, Kern FH, Reves JGThe role of continuous jugular venous saturation monitoring during cardiac surgery with cardiopulmonary bypass. Anesth Analg. l992;74:627-629.
63 Schell RM, Cole DJ. Cerebral monitoring: jugular venous oximetry.Anesth Analg. 2000 90:559-566.
64 Sakamoto T, Zurakowski D. Interaction of temperature with hematocrit level and pH determines safe duration of hypothermic circulatory arrest.. J Thorac Cardiovasc Surg.2004;128:220-232.
65 Morimoto Y, Niida Y. Changes in cerebral oxygenation in children undergoing surgical repair of ventricular septal defects. Anaesthesia.2003;58:77-83.
66 Shaaban AM, Harmer M. A pilot study of evaluation of cerebral function by S100beta protein and near-infrared spectroscope during cold and warm cardiopulmonarybypass in infants and children undergoing open-heart surgery. Anaesthesia .2004;59:20-26.
67 Andropoulos DB, Stayer SA. Neurological monitoring for congenital heart surgery. Anesth Analg.2004;99:1365-1375.
68 Diegeler A, Hirsch R, Schneider F, Schilling LO, Falk V, Rauch T, Mohr FW.Neuromonitoring and neurocognitive outcome in off pump versus conventional coronary bypass operation.Ann T'horac Surg. 2000;69:1162-1166.
69 Persson L, Hardemark HG Gustafsson J, Rundstrom G, Mendel-Hartvig I, Esscher T, Pahlman S.S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system. Stroke. 1987; 18:911-918.
70 Gao F, Harris DN, Sapsed-Byrne S. Time course of neurone-specific enolase and S-100 protein release during and after coronary artery bypass grafting. Br J Anaesth.l999;82:266-267.
71 Johnsson P, Backstrom M, Bergh C, et al.Increased S 100B in blood after cardiac surgery is a powerful predictor of late mortality. Ann Thorac Surg. 2003;75:162-168.
72 Basile AM, Fusi C, Conti AA, et al. S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery: preliminary observation of a 6-month follow-up study.Eur Neurol. 2001;45:151-159.
73 Nakamura K, Ueno T, Yamamoto H, et al.Relationship between cerebral injury and inflammatory responses in patients undergoing cardiac surgery with cardiopulmonary bypass. Cytokine. 2005;29:95-104.
74 Svenmarker SEngstrom KG Karlsson T, et al.Influence of pericardia! suction blood retransfusion on memory function and release of protein S100B. Perfusion. 2004; 19:337-343.
75 Fazio V, Bhudia SK, Marchi N, Aumayr B, Janigro D. Peripheral detection of S100beta during cardiothoracic surgery: what are we really measuring?Ann Thorac Surg.2004;78:46-52;discussion 52-3.
76 Nathan HJ, Wells GA, Munson JL, Wozny D. Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass. Circulation.2001;104(Suppl. 1):85-91.
77 Grigore AM, Grocott HP, Mathew J et al. The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery. Anesth Analg.2002; 94: 4-10.
78 Busto R, Globus MY, Dietrich WD, Martinez E, Valdes I, Ginsberg MD. Effect of mild hypothermia on ischemiainduced release of neurotransmitters and free fatty acids in rat brain.Stroke. 1989; 20: 904-910.
79 Jones TJ, Stump DA, Deal DD, Vemon JC, Manuel JC. Hypothermia protects the brain from embolization by reducing and redirecting the embolic load. Ann Thorac Surg.l999;68:1465.
80 Grocott HP, Mackensen B, Grigore AM et al. Postoperative hyperthermia is associated with cognitive dysfunction after coronary artery bypass graft surgery. Stroke.2002;33:537-41.
81 Barbut D, Grassineau D, Lis E, et al. Posterior distribution of infarcts in strokes related to cardiac operations. Ann Thorac Surg.1998;65:1656-1659.
82 Sadahiro M, Haneda K, Mohri H. Experimental study of cerebral autoregulation during cardiopulmonary bypass with or without pulsatile perfusion. J Thorac Cardiovasc Surg.1994; 108:446-454.
83 Murkin JM, Martzke JS, Buchan AM, et al. A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery. I. Mortality and cardiovascular morbidity. II. Neurologic and cognitive outcome J Thorac Cardiovasc Surg.1995; 110:340-62.
84 Kirklin JW, Barrat-Boyes BG. Hypothermia, circulatory arrest, and cardiopulmonary bypass.In: Cardiac surgery. New York: Churchill Livingstone. 1993:62-73.
85 Mathew J, Grocott H, Phillips-Bute B, et al. Extreme hemodilution is associated with increased cognitive dysfunction in the elderly after cardiac surgery. Anesth Analg.2004;98:SCA21.
86 Jonas RA, Wypij D, Roth SJ, et al. The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants. J Thorac Cardiovasc Surg.2003; 126:1765-1774.
87 Bathein G, Townes B.A randomized trial of carbon dioxide management during hypothermic cardiopulmonary bypass. Anesthesiology.l990;72:7-15.
88 Stephan H, Weyland A.Acid-base management during hypothermic cardiopulmonary bypass does not affect cerebral metabolism but dose affect blood flow and neurological outcome. Br J Anaesth.l992;69:51-57.
89 du Plessis AJ, Jonas RA, Wypij D, et al. Perioperative effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg.1997;114:991-1001.
90 Aoki M, Nomura F. Effects of pH on brain energetics after hypothermic circulatory arrest.Ann Thorac Surg.1993;55:1093-1103.
91 Bellinger DC, Wypij D, du Plessis AJ, et al. Developmental and neurologic effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg.2001; 121:374-383.
92 De Ferranti S, Gauvreau K, Kickey PR, et al. Intraoperative hyperglycemia during infant cardiac surgery is not associated with adverse neurodevelopmental outcomes at 1,4, and 8 years. Anesthesiology.2004; 100:1339-1341.
93 Butterworth J, Wagenknecht LE, Legault C, et al. Attempted control of hyperglycemia during cardiopulmonary bypass fails to improve neurologic or neurobehavioral outcomes in patients without diabetes mellitus undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg.2005; 130:1319-1325.
94 Gaynor JW, Nicolson SC. Increasing duration of deep hypothermic circulatory arrest is associated with an increased incidence of postoperative electroencephalographic seizures. J Thorac Cardiovasc surg.2005; 130:1278-1286.
95 Williams GD.Ramamoorthy C. Brain monitoring and protection during pediatric cardiac surgery. Semin Cardiothorac Vasc Anesth. 2007; 11:23-33.
96 Reichenspurner H, Navia JA, Berry G et al. Paniculate emboli capture by an intra-aortic filter device during cardiac surgery. J Thorac Cardiovasc Surg.2000;119:233-241.
97 Bergman P,Hadjinikolaou L, van der Linden J.Aortic atheroma is related to number of particulates captured by intra-aortic filtration in CABG. Eur J Cardiothorac Surg.2002;22:539-544.
98 White BC, Sullivan JM, DeGarcia DJ, et al. Brain ischemia and reperfusion: molecular mechanism of neuronal injury. J Neurol Sci.2000; 179:1 -33.
99 Brock MV, Blue ME, Lowenstein CJ, et al. Induction of neuronal nitric oxide following hypothermic circulatory arrest. Ann Thorac Surg. 1996;62:1313-1320.
100 Nussmeier NA, Arlund C, Slogoff S. Neuropsychiatric complications after cardiopulmonary bypass: cerebral protection by a barbiturate. Anesthesiolgy.1986;64:165-170.
101 Zaidan JR, Klochany A, Martin WM, et al. Effect of thiopental on neurologic outcome following coronary artery bypass grafting. Anesthesiology. 1991 ;74:406-411.
102 Roach GW, Newman MF, Murkin JM, et al., for the Multicenter Study of Perioperative Ischemia (McSPI) Research Group. Ineffectiveness of burst suppression therapy in mitigating perioperative cerebrovascular dysfunction. Anesthesiology.1999;90:1255-1264.
103 Hindman BJ, Todd MM. Improving neurologic outcome after cardiac surgery.Anesthesiology. 1999;90:1243-1247.
104 Arrowsmith JE, Harrison MJ, Newman SP, et al. Neuroprotection of the brain during cardiopulmonary bypass: a randomized trial of remacemide during cardiopulmonary bypass.Stroke.1998;29:2357-2362.
105 Mitchell SJ, Pellet O, Gorman DF. Cerebral protection by lidocaine during cardiac operations.Ann Thorac Surg.1999;67:1117-1124.
106 Wang D, Wu X, Li J, et al. The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery. Anesth Analg.2002;95:1134-1141.
107 Mathew JP, Shernan SK, White WD, et al. Preliminary report of the effects of complement suppression with pexelizumab on neurocognitive decline after coronary artery bypass graft surgery. Stroke.2004;35:2335-2339.
108 Levy J, Pifarre R, Schaff H, et al. A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood los and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting. Circulation. 1995;92:2236-2244.
109 Harmon DC, Ghori KG, Eustace NP, et al. Aprotinin decreases the incidence of cognitive deficit following CABG and cardiopulmonary bypass: a pilot randomized controlled study.Can J Anaesth.2004;51:1002-1009.
110 Ferguson TB, Coombs LP, Peterson ED. Preoperative beta-blocker use and mortality and morbidity following CABG surgery in North America. JAMA.2002;287:2221-2227.
111 Amory DW, Grigore A, Amory JK et al. Neuroprotection is associated with beta-adrenergic receptor antagonists during cardiac surgery: evidence from 2575 patients. J Cardiothorac Vasc Anesth.2002;16:270-277.
112 Mocchetti I. Exogenous gangliosides,neuronal plasticity and repair, and the neurotrophins.Cell Mol Life Sci.2005;62:2283-2294.
113 Alter M. GM1 ganglioside for acute ischemic stroke: trial design issues. Ann N Y Acad Sci. 1998;845:391 -401.
114 Geisler FH. Clinical trials of pharmacotherapy for spinal cord injury. Ann N Y Acad Sci.1998;845:374-381.
115 Giacinto G, Marilyn H, Alfred T, et al. Evaluating neuroprotective agents for clinical antiischemic benefit using neuropsychological changes after cardiac surgery under cardiopulmonary bypass Methodological strategies and results of a double-blind,placebo-controlled trial of GM1 ganglioside. Stroke.1996;27:858-874.
116 Redmond JM, Gillinov AM, Blue ME,et,al. The monosialoganglioside, GM1, reduces neurologic injury associated with hypothermic circulatory arrest. Surgery. 1993; 114:324-332.
117 Phillis JW, O'ReganMH. GM1 ganglioside inhibits ischemic release of amino acid neurotransmitters from rat cortex. Neuroreport.1995;6:2010-2012.
118 Liu JR ,Ding MP ,Wei EQ , et al. Monosialoganglioside prevented ischemic rat hippocampal slices through stabilizing expression of N - methyl - D - aspartate receptor subunit . Acta Pharmacol Sin.2004;25:727-732.
119 Avrova NF, Shestak KI, Zakharova 10, et al. The use of antioxidants to prevent glutamate-induced derangement of calcium ion metabolism in rat cerebral cortex synaptosomes. Neurosci Behav Physiol.2000;30:535-541.
120 Tseng EE ,Brock MV ,Lange MS , et al . Monosialoganglioside GM1 inhibits neurotoxicity after hypothermic circulatory arrest. Surgery. 1998; 124:298-306.
121 Rabin SJ, BachisA, Mocchetti I. Gangliosides activate Trk receptors by inducing the release of neurotrophins. J Biol Chem.2002;277: 49466-49472.