肝硬化患者复合瑞芬太尼时异丙酚的药代动力学

目的 研究肝硬化患者复合瑞芬太尼时异丙酚的药代动力学.方法拟在内镜下行食道静脉曲张套扎术的肝硬化患者10例(试验组);拟行胃镜检查术患者10例(对照组),肝功能未见异常,男女各半,年龄18～55岁,体重40～75 kg.静脉注射异丙酚1.5 mg/kg和瑞芬太尼0.5 μg/kg,5 min后再次静脉注射异丙酚0.5 mg/kg和瑞芬太尼0.2 μg/kg.分别于给药前、给药后2、5、10、15、20、30、45、60、80、120 min时采集桡动脉血样,采用气相色谱质谱联用法测定血浆异丙酚浓度,采用DAS 2.0软件计算药代动力学有关指标.结果 异丙酚的血药浓度.时间曲线符合开放性三室模型;与对照组比较,试验组分布半衰期、消除半衰期、终末半衰期、血药浓度-时间曲线下面积和转运速率常数差异无统计学意义(P＞0.05),表观分布容积和清除率升高(P＜0.01).结论 肝硬化患者复合瑞芬太尼麻醉时,异丙酚的表观分布容积和清除率升高,而其他药代动力学参数无明显变化.

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Objective To investigate the pharmacokinetics of propofol when combined with remifentanil in patients with liver cirrhosis.Methods Ten patients (5 males, 5 females) with liver cirrhosis scheduled for endoscopic esophageal varix ligation (test group) and 10 cases (5 males, 5 females) with normal liver function scheduled for gastroscopy (control group), aged 18-55 yr, weighing 40-75 kg, were studied. The patients were unpremedicated. All the patients received iv injection of propofol 1.5 mg/kg and remifentanil 0.5 μg/kg, and 5 min later propofol 0.5 mg/kg and remifentanil 0.2 μg/kg was given again. Blood samples were taken from radial artery before administration and at 2, 5, 10, 15, 20, 30, 45, 60, 80 and 120 min after administration for determination of the plasma propofol concentration using gas chromatography-mass spectrography. The pharmacokinetic parameters were calculated using DAS 2.0 software.Results The pharmacokinetics of propofol was best described by a three-compartment open model. There was no significant difference in the distribution half-life, elimination halflife , terminal half-life, area under the curve and transfer rate constant between the two groups ( P ＞ 0.05) . The apparent volume of distribution of propofol and clearance were significantly increased in test group compared with control group (P ＜0.01) .Conclusion When propofol combined with remifentanil is used in patients with liver cirrhosis, the apparent volume of distribution of propofol and clearance are significantly increased, while no changes in the other pharmacokinetic parameters are found.     

颈内动脉输注异丙酚对胶质瘤切除术患者的脑保护作用

目的 探讨颈内动脉输注异丙酚对胶质瘤切除术患者的脑保护作用.方法 择期胶质瘤切除术患者40例和立体定向胶质瘤活检术患者20例,年龄40～64岁,体重48～73 kg.采用随机数字表法,将拟行胶质瘤切除术患者随机分为2组(n=20):颈内动脉给药组(IA组)和静脉给药组(Ⅳ组).拟行立体定向胶质瘤活检术患者为对照组(C组),采用2%利多卡因15～20 ml术野局部浸润麻醉.IA组和Ⅳ组采用异丙酚-瑞芬太尼-罗库溴铵行麻醉诱导.IA组麻醉诱导后行颈内动脉穿刺置管,颈内动脉靶控输注异丙酚.两组术中调整异丙酚和瑞芬太尼靶浓度,维持BIS值40～60.间断静脉注射罗库溴铵.术中取胶质瘤组织标本,采用免疫组化法测定胶质瘤组织水通道蛋白1(AQP1)和AQP4表达.于麻醉诱导前(T1)、切皮时(T2)、术毕时(T3)、拔除气管导管时(T4)记录MAP和HR;记录手术时间、麻醉用药情况.结果 与T1时比较,Ⅳ组T2,3时MAP和HR降低(P＜0.05),IA组各时点MAP和HR比较差异无统计学意义(P＞0.05).与IA组比较,Ⅳ组MAP和HR降低(P＜0.05).与C组比较,IA组和Ⅳ组AQP1和AQP4表达下调(P＜0.05).与Ⅳ组比较,IA组异丙酚用量减少(P＜0.05),AQP1和AQP4表达、瑞芬太尼和罗库溴铵用量、手术时间比较差异无统计学意义(P＞0.05).结论 与静脉输注异丙酚相比,颈内动脉途径给药不仅可减少胶质瘤切除术患者异丙酚的用量,而且对其脑保护作用没有影响.

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Objective To investigate the cerebral protective effect of intracarotid infusion of propofol in patients undergoing resection of cerebral gliomas. Methods Sixty ASA Ⅰ- Ⅲ patients with cerebral glioma aged 40-64 yr weighing 48-73 kg were enrolled in this study. Forty patients undergoing resection of glioma under general anesthesia were randomly divided into 2 groups ( n = 20 each): intracarotid propofol group (group IA ) and intravenous propofol group (group Ⅳ). Twenty patients undergoing biopsy of glioma under local infiltration anesthesia with 2% lidocaine 15-20 md served as control group (group C). In IA and Ⅳ groups anesthesia was induced with TCI of propofol and remifentanil. Tracheal intubation was facilitated with rocuronium 0.6 mg/kg. The patients were mechanically ventilated. PErCO2 was maintained at 35-45 mm Hg. Anesthesia was maintained with TCI of propofol and remifentanil and intermittent iv boluses of rocuronium. In group IA internal carotid artery was cannulated after induction of anesthesia and propofol was administered by TCI via carotid artery while remifentanil was administered by TCI via peripheral vein. BIS was maintained at 40-60 during operation. ECG, MAP, HR, SpO2, PETCO2 and BIS were continuously monitored. MAP and HR were recorded before induction of anesthesia (T1) ,during skin incision (T2 ), at the end of operation (T3), during extubation ( T4 ). The glioma specimens were obtained for microscopic examination and determination of aquaporin 1 and aquaporin 4 ( AQP1, AQP4) expression by immunohistochemistry. Results MAP and HR were significantly decreased at T2 and T3 as compared with the baseline at T1 in group Ⅳ ( P ＜ 0.05), while there was no significant change in MAP and HR after induction of anesthesia in group IA ( P ＞ 0.05). The expression of AQP1 and AQP4 was down-regulated in IA and Ⅳ groups compared with group C (P ＜0.05). The propofol consumption during anesthesia was significantly less in group IA than in group Ⅳ (P ＜0.05). There was no significant diffe-rence in AQP1 and AQP4 expression, the amount of remifentanil and recuronium consumed and duration of operation betweenIA and Ⅳ groups ( P ＞ 0.05). Concltsion Intracarotid propofol can decrease the amount of propofol needed for maintenance of anesthesia as compared with intravenous administration and attenuate brain edema,indicating cerebral protective effect.     

缺血后处理对大鼠肝缺血再灌注时肝细胞线粒体膜通透性转换和膜电位的影响

目的 评价缺血后处理对大鼠肝缺血再灌注时肝细胞线粒体膜通透性转换和膜电位(△Ψm)的影响.方法 成年健康雄性SD大鼠40只,体重220～260 g,采用随机数字表法,将其随机分为5组(n=8):假手术组(S组)、苍术苷+假手术组(A+S组)、缺血再灌注组(IR组)、缺血后处理组(IPO组)和苍术苷+缺血后处理组(A+IPO组).采用阻断肝中叶和左叶60 min,恢复血流灌注6 h的方法 建立大鼠肝缺血再灌注模型.S组和A+S组仅游离肝门,不阻断血管;A+S组关腹前静脉注射苍术苷5 mg/kg;IR组制备肝缺血再灌注模型;IPO组于再灌注前行缺血后处理,再灌注1 min,缺血1 min,反复3次;A+IPO组于再灌注前静脉注射苍术苷5 mg/kg.于缺血前即刻和再灌注6 h时,采集左颈静脉血样,测定血清ALT和AST的活性.再灌注6 h时处死大鼠,取肝左叶组织,观察超微结构和细胞凋亡情况,计算凋亡指数,测定细胞色素c(Cyt c)的表达水平、△Ψm和线粒体通透性转换孔(MPTP)活性.结果 与S组比较,A+S组时血清ALT和AST的活性、凋亡指数、Cyt c表达、△Ψm和MPTP活性差异无统计学意义(P＞0.05),IR组、IPO组和A+IPO组再灌注6 h时血清ALT和AST的活性、凋亡指数升高,Cyt c表达上调,△Ψm降低,MPTP活性升高(P＜0.05);与IR组比较,IPO组血清ALT和AST的活性、凋亡指数降低,Cyt c表达下调,△Ψm升高,MPTP活性降低(P＜0.05),肝组织病理学损伤减轻,A+IPO组各指标差异无统计学意义(P＞0.05);与IPO组比较,A+IPO组血清ALT和AST的活性、凋亡指数升高,Cyt c表达上调,△Ψm降低,MPTP活性升高(P＜0.05),肝组织病理学损伤加重.结论 缺血后处理可抑制肝细胞线粒体膜通透性转换,减少线粒体△Ψm的耗散,从而减轻大鼠肝缺血再灌注损伤.

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Objective To investigate the effects of ischemic postconditioning on mitochondrial permeability transition and mitochondrial transmembrane potential(△Ψm)following hepatic ischemia-reperfusion(I/R)in rats.Methods Forty male SD rats weighing 220-260 g were randomly divided into 5 groups with 8 animals in each group:sham operation group(group S);atractyloside+sham operation group(group A+S);I/R group;ischemic postconditioning group(group IPO)and atractyloside+ischemic postconditioning group(group A+IPO).The animals were anesthetized with intramuscular injection of atropine 0.05 mg/kg.Hepatic I/R was produced by occlusion of hepatic blood flow for 60 min followed by 6 h reperfusion.In group A+S,atractyloside 5 mg/kg was injected intravenously before abdomen Was closed.In group IPO,the animals were subjected to 3 cycles of 1 min reperfusion interspersed with 1 min hepatic isehemia at the end of 60 min hepatic ischemia.In group A+IPO,atractyloside 5 mg/kg was injected intravenously before reperfusion. Venous blood samples were collected for determination of serum ALT and AST activities immediately before ischemia and at 6 h of reperfusion. The animals were then sacrificed.Their livers were removed for microscopic examination, detection of apoptosis and determination of cytochrome c (Cyt c) expression, △Ψm and mitochonerial permeability transition pore (MPTP)activity. Apoptosis index (AI) was calculated. Results There was no significant difference in serum ALT and AST activities, AI, Cyt c expression, △Ψm and MPTP activity between S and A + S groups (P＞0.05). Compared with group S, serum ALT and AST activities and AI were significantly increased, Cyt c expression was up-regulated, △Ψm was decreased and MPTP activity was increased in groups I/R, IPO and A+IPO(P＜0.05).Compared with group I/R, serum ALT and AST activities and AI were significantly decreased,Cyt c expression was down-regulated, △Ψm was increased and MPTP activity was decreased in group IPO(P＜0.05), while no significant change was found in group A+IPO(P＞0.05).Compared with group IPO,serum ALT and AST activities and AI were significantly increased, Cyt c expression was up-regulated, △Ψm was decreased and MPTP activity was increased in group A + IPO(P＜ 0.05).Microscopic examination showed that hepatic injury was reduced in group IPO compared with group I/R, while aggravated in group A+ IPO compared with group IPO. Conclusion Ischemic postconditioning can protect liver from I/R injury by attenuating the I/R-induced increase in MPTP opening and decrease in △Ψm in rats.     

小剂量氯胺酮对抑郁大鼠异丙酚麻醉下电休克疗效的影响

目的 评价小剂量氯胺酮对抑郁大鼠异丙酚麻醉下电休克疗效的影响.方法 成年雄性SD大鼠60只,体重200～250 g,采用慢性不可预见轻度应激建立抑郁模型.采用随机数字表法,将大鼠随机分为6组(n=10):对照组(C组)、抑郁组(D组)、异丙酚组(P组)、异丙酚+电休克治疗组(PE组)、氯胺酮+异丙酚组(KP组)和氯胺酮+异丙酚+电休克治疗组(KPE组).C组不作任何处理;P组和PE组腹腔注射异丙酚100mg/kg,KP组和KPE组腹腔注射氯胺酮10 mg/kg和异丙酚80mg/kg,待翻正反射消失后,将电极夹在双侧鼠耳,P组和KP组不通电,PE组和KPE组通电治疗,1次/d,连续7 d.分别于建模前、建模后和治疗结束后,行糖水消耗(SFC)实验,计算SFC百分比;行Morris水迷宫实验,测试学习记忆功能.结果 与C组比较,建模后D组、P组、FE组、KP组及KPE组SFC百分比降低,逃避潜伏期延长,目标象限停留时间缩短(P＜0.05),治疗后KPE组SFC百分比、逃避潜伏期及目标象限停留时间差异无统计学意义(P＞0.05).与D组比较,治疗后KPE组SFC百分比升高(P＜0.05),逃避潜伏期及目标象限停留时间差异无统计学意义(P＞0.05),FE组SFC百分比升高,逃避潜伏期延长,目标象限停留时间缩短(P＜0.05).与PE组比较,治疗后KPE组SFC百分比升高,逃避潜伏期缩短,目标象限停留时间延长(P＜0.05).结论 小剂量氯胺酮不仅可增强异丙酚麻醉下电休克治疗抑郁大鼠的效果,还可进一步减轻电休克所致认知功能损害.

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Objective To evaluate the effect of low-dose ketamine on the efficacy of electroconvulsive therapy (ECT) under propofol anesthesia in depressed rats. Methods Sixty adult male SD rats weighing 200-250 g were used in this study. The depression model was established by chronic unpredictable mild stress (CUMS). The animals were then randomly divided into 6 groups (n = 10 each): control group (group C), depression group (group D), propofol group ( group P), propofol + ECT group ( group PE), ketamine + propofol group ( group KP), and ketamine + propofol + ECT group (group KPE). Groups P and KP received intraperitoneal propofol 100 mg/kg and ketamine 10 mg/kg + propofol 80 mg/kg respectively, and groups PE and KPE received ECT after intraperitoneal injection of propofol 100 mg/kg and ketamine 10 mg/kg + propofol 80 mg/kg respectively once a day for 7 consecutive days. All rats underwent sucrose fluid consumption and Morris water maze tests before CUMS, after CUMS, and after treatment. Results Compared with group C, the sucrose consumption percentage was significantly decreased, the escape latency was prolonged, and the time spent in the target quadrant (the original platform quadrant) was shortened after CUMS in D, P, PE, KP and KE groups ( P ＜ 0.05). Compared with group D,the sucrose consumption percentage was significantly increased (P ＜ 0.05), while no significant change in the escape latency and time spent in the target quadrant was found after treatment in group KPE ( P ＞ 0.05 ), and the sucrose consumption percentage was significantly increased, the escape latency was prolonged, and the time spent in the target quadrant was shortened after treatment in group PE ( P ＜ 0.05). Compared with group PE, the sucrose consumption percentage was significantly increased, the escape latency was shortened, and the time spent in the target quadrant was prolonged after treatment in group KPE ( P ＜ 0.05). Conclusion Low-dose ketamine can not only enhance the efficacy of ECT under propofol anesthesia in depressed rats, but also reduce cognitive impairment induced by ECT.     

异丙酚对氯胺酮诱发新生大鼠脑损伤的影响

目的 探讨异丙酚对氯胺酮诱发新生大鼠脑损伤的影响.方法 新生SD大鼠80只,日龄7 d,雌雄不拘,体重12～20 g,采用随机数字表法,将大鼠随机分为4组(n=20):生理盐水对照组(NS组)腹腔注射生理盐水1 ml;氯胺酮致脑损伤组(K组)、异丙酚对照组(P组)和异丙酚+氯胺酮组(PK组)分别腹腔注射氯胺酮70mg/kg、异丙酚70mg/kg、异丙酚70mg/kg+氯胺酮70mg/kg,每隔2 h注射1次,共3次.于苏醒后24 h时各组随机取10只大鼠,处死后取海马组织,采用TUNEL法检测海马CA1区神经元凋亡情况,计算凋亡率,采用免疫组化法检测Bcl-2和Bax的蛋白表达,腹腔注射后21d时各组余大鼠采用Morris水迷宫实验测定学习记忆功能(逃避潜伏期和穿越平台次数).结果 与NS组相比,K组神经元凋亡率升高,P组和PK组Bcl-2蛋白表达上调,其余各组Bax蛋白表达上调,逃避潜伏期延长,穿越平台次数减少(P＜0.05或0.01);与K组相比,PK组神经元凋亡率降低,P组Bax蛋白表达下调,P组和PK组Bcl-2蛋白表达上调,逃避潜伏期缩短,穿越平台次数增加(P＜0.05).结论 异丙酚可减轻氯胺酮诱发新生大鼠的脑损伤,可能与其调节Bcl-2和Bax蛋白表达从而抑制海马神经元凋亡有关.

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Objective To investigate the effect of propofol on the cerebral injury induced by ketamine in neonatal rats. Methods Eighty 7-day-old SD rats of both sexes, weighing 12-20 g, were randomly divided into 4 groups (n = 20 each): normal saline (NS) group, ketamine-induced cerebral injury group (group K), propofol group (group P) and propofol combined with ketamine group (group PK). Group NS received intraperitoneal NS 1 ml. In groups K, P and PK, ketamine 70 mg/kg, propofol 70 mg/kg and propofol 70 mg/kg + ketamine 70 mg/kg were injected intraperitoneally once every 2 h for 3 times respectively. Ten rats in each group were selected and sacrificed at 24 h after emergence from anesthesia and the hippocampi obtained to determine the neuronal apoptosis (by TUNEL) and Bcl-2 and Bax protein expression(by immunohitochemistry). The apoptosis rate was calculated.The other 10 rats in each group were selected at 21 days after the intraperitoneal injection and the learning and memory functions (escape latency and frequency of crossing the original platform) were evaluated using Morris water maze. Results Compared with group NS, the apoptosis rate was significantly increased in group K, Bcl-2 protein expression was up-regulated in groups P and PK, and Bax protein expression was up-regulated, the escape latency was significantly prolonged and the frequency of crossing the original platform was significantly decreased in the other groups (P ＜ 0.05 .or 0.01 ). Compared with group K, the apoptosis rate was significantly decreased in group PK, Bax protein expression was down-regulated in group P, and Bcl-2 protein expression was up-regulated,the escape latency was significantly shortened and the frequency of crossing the original platform was significantlyincreased in groups P and PK ( P ＜ 0.05). Conclusion Propofol can reduce the cerebral injury induced by ketamine in neonatal rats, and the regulation of the Bcl-2 and Bax protein expression and inhibition of the neuronal apoptosis in hippocampus may be involved in the mechanism.     

不同麻醉方法对神经外科手术患者脑血管自身调节功能影响的比较

目的 比较不同麻醉方法对神经外科手术患者脑血管自身调节功能的影响.方法 拟行颅脑肿瘤切除术患者69例,ASA分级Ⅱ或Ⅲ级,年龄23～62岁,采用随机数字表法,将患者随机分为3组(n=23):异丙酚-瑞芬太尼复合麻醉组(PR组)、七氟醚.瑞芬太尼复合麻醉组(SR组)和异丙酚-七氟醚-瑞芬太尼复合麻醉组(PSR组).麻醉诱导:PR组和PSR组TCI异丙酚,血浆靶浓度为3μg/ml;SR组吸入8%七氟醚;3组均静脉注射瑞芬太尼1 mg/kg和阿曲库铵0.5 mg/kg.气管插管后机械通气,维持PETCO2 32～35 mm Hg.麻醉维持:PR组TCI异丙酚,血浆靶浓度2.0～3.5/μg/ml,SR组吸入1.5%～2.5%七氟醚,PSR组TCI异丙酚(血浆靶浓度1.5～3.0 μg/ml)复合吸入1%七氟醚,3组均TCI瑞芬太尼(血浆靶浓度2.0～4.5 ng/ml),静脉输注阿曲库铵6 μg·kg-1·min-1,维持听觉诱发电位指数值40～45.分别于麻醉诱导前(基础状态,T0)、气管插管后即刻(T1)、打开颅骨前即刻(T2)及开始缝皮时(T3)记录大脑中动脉时间-平均峰值流速,于相应时点压迫一侧颈总动脉7 s,计算脑短暂充血反应率(THRR),以反映脑血管自身调节功能.结果 与T0时比较,PR组T2时THRR升高,SR组T2,3时THRR降低(P<0.05),PSR组THRR差异无统计学意义(P>0.05).与PR组比较,SR组和PSR组THRR降低(P<0.05);与SR组比较,PSR组THRR升高(P<0.05).结论 异丙酚-瑞芬太尼复合麻醉可提高神经外科手术患者脑血管自身调节功能,七氟醚-瑞芬太尼复合麻醉可降低其脑血管自身调节功能,异丙酚-七氟醚-瑞芬太尼复合麻醉对其脑血管自身调节功能无影响.

Abstract：

Objective To compare the effect of different methods of anesthesia on cerebral autoregulation in patients undergoing neurosurgery.Methods Sixty-nine ASA Ⅱ orⅢ patients with brain tumor, aged 23-62 yr, scheduled for neurosurgery under general anesthesia, were randomly divided into 3 groups ( n = 23 each) : propofol-remifentanil group (group PR), sevoflurane-remifentanil group (group SR) and propofol-sevoflurane-remifentanil group (group PSR) . Anesthesia was induced with target-controlled infusion (TCI) of propofol (target plasma concentration3 μg/ml, PR and PSR groups) or inhalation of 8% sevoflurane (group SR) and iv injection of remifentanil 1 mg/kg and atracurium 0.5 mg/kg. The patients were mechanically ventilated after tracheal intubation. PETCO2 was maintained at 32-35 mm Hg. Anesthesia was maintained with TCI of propofol (target plasma concentration 2.0-3.5 μg/ml) in group PR, with inhalation of 1.5%-2.5% sevoflurane in group SR, with TCI of propofol (target plasma concentration 1.5-3.0 μg/ml) and inhalation of 1% sevoflurane in group PSR, and with TCI of remifentanil (target plasma concentration 2.0-4.5 ng/ml) and iv infusion of atracurium at 6 μg · kg-1 · min-1 in all groups. Auditory evoked potential index was maintained between 40-45. The middle cerebral artery time-average peak flow velocity was recorded before induction (baseline) , immediately after intubation, immediately before craniotomy and at the beginning of skin suture. The unilateral carotid artery was compressed for 7 s at the corresponding time points mentioned above. The transient hyperemic response ratio (THRR) was calculated to reflect cerebral autoregulation. Results Compared with the baseline value at T0, THRR was significantly increased at T2in group PR and decreased at T2,3 in group SR (P <0.05) ,while no significant change was found in THRR at T1-3in group PSR (P >0.05). The THRR was significantly lower in SR and PSR groups than in group PR, and higher in group PSR than in group SR ( P < 0.05). Conclusion Propofol-remifentanil anesthesia can improve cerebral autoregulation, sevoflurane-remifentanil anesthesia can reduce cerebral autoregulation, and propofol-sevofluraneremifentanil anesthesia exerts no effect on cerebral autoregulation in patients undergoing neurosurgery.     

高渗氯化钠羟乙基淀粉40注射液高容量血液稀释对大鼠肝脏缺血再灌注损伤的影响

Objective To investigate the effects of hypervolemic hemodilution (HH) with hypertonic saline plus hetastarch solution 40 injectio on hepatic ischemia-reperfusion (I/R) injury in rats. Methods Thirty male Wistar rats weighing 300-350 g were randomly divided into 3 groups ( n = 10 each): group I sham operation (group S); group II I/R and group Ⅲ HH. Partial liver ischemia was produced by clamping hepatic portal vein and left arteria hepatica for 30 min with atraumatic mini-clamp, followed by 2 h of reperfusion in I/R group and HH group. In HH group the animals were infused hypertonic saline plus hetastarch solution 40 injectio 10 ml/kg through vena caudalis over 30 min and then hepatic I/R was performed IS min after the infusion.The animals were killed at 2 h of reperfusion. The left liver was removed and blood sample was taken from inferior caval vein for determination of (1) serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities; (2) superoxide dismutase ( SOD) activity and malondialdehyde ( MDA) content in the liver; ( 3 ) microscopic examination. Results The serum ALT and AST activities and MDA content in the liver were significantly higher, SOD activity in the liver significantly lower after hepatic I/R and pathological changes in the liver severer in group I/R and HH than in group S. The serum ALT and AST activities and MDA content in the liver were significantly lower, SOD activity in the liver significantly higher after hepatic I/R and pathological changes in the liver milder in group HH than in group I/R. Conclusion Hypervolemic hemodilution with hypertonic saline plus hetastarch solution 40 injectio can ameliorate hepatic I/R injury by decreasing oxygen free radical production in rats.     

高渗氯化钠羟乙基淀粉40注射液高容量血液稀释对大鼠肝脏缺血再灌注损伤的影响

Objective To investigate the effects of hypervolemic hemodilution (HH) with hypertonic saline plus hetastarch solution 40 injectio on hepatic ischemia-reperfusion (I/R) injury in rats. Methods Thirty male Wistar rats weighing 300-350 g were randomly divided into 3 groups ( n = 10 each): group I sham operation (group S); group II I/R and group Ⅲ HH. Partial liver ischemia was produced by clamping hepatic portal vein and left arteria hepatica for 30 min with atraumatic mini-clamp, followed by 2 h of reperfusion in I/R group and HH group. In HH group the animals were infused hypertonic saline plus hetastarch solution 40 injectio 10 ml/kg through vena caudalis over 30 min and then hepatic I/R was performed IS min after the infusion.The animals were killed at 2 h of reperfusion. The left liver was removed and blood sample was taken from inferior caval vein for determination of (1) serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities; (2) superoxide dismutase ( SOD) activity and malondialdehyde ( MDA) content in the liver; ( 3 ) microscopic examination. Results The serum ALT and AST activities and MDA content in the liver were significantly higher, SOD activity in the liver significantly lower after hepatic I/R and pathological changes in the liver severer in group I/R and HH than in group S. The serum ALT and AST activities and MDA content in the liver were significantly lower, SOD activity in the liver significantly higher after hepatic I/R and pathological changes in the liver milder in group HH than in group I/R. Conclusion Hypervolemic hemodilution with hypertonic saline plus hetastarch solution 40 injectio can ameliorate hepatic I/R injury by decreasing oxygen free radical production in rats.     

高渗氯化钠羟乙基淀粉40注射液高容量血液稀释对大鼠肝脏缺血再灌注损伤的影响

Objective To investigate the effects of hypervolemic hemodilution (HH) with hypertonic saline plus hetastarch solution 40 injectio on hepatic ischemia-reperfusion (I/R) injury in rats. Methods Thirty male Wistar rats weighing 300-350 g were randomly divided into 3 groups ( n = 10 each): group I sham operation (group S); group II I/R and group Ⅲ HH. Partial liver ischemia was produced by clamping hepatic portal vein and left arteria hepatica for 30 min with atraumatic mini-clamp, followed by 2 h of reperfusion in I/R group and HH group. In HH group the animals were infused hypertonic saline plus hetastarch solution 40 injectio 10 ml/kg through vena caudalis over 30 min and then hepatic I/R was performed IS min after the infusion.The animals were killed at 2 h of reperfusion. The left liver was removed and blood sample was taken from inferior caval vein for determination of (1) serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities; (2) superoxide dismutase ( SOD) activity and malondialdehyde ( MDA) content in the liver; ( 3 ) microscopic examination. Results The serum ALT and AST activities and MDA content in the liver were significantly higher, SOD activity in the liver significantly lower after hepatic I/R and pathological changes in the liver severer in group I/R and HH than in group S. The serum ALT and AST activities and MDA content in the liver were significantly lower, SOD activity in the liver significantly higher after hepatic I/R and pathological changes in the liver milder in group HH than in group I/R. Conclusion Hypervolemic hemodilution with hypertonic saline plus hetastarch solution 40 injectio can ameliorate hepatic I/R injury by decreasing oxygen free radical production in rats.     

高渗氯化钠羟乙基淀粉40注射液高容量血液稀释对大鼠肝脏缺血再灌注损伤的影响

Objective To investigate the effects of hypervolemic hemodilution (HH) with hypertonic saline plus hetastarch solution 40 injectio on hepatic ischemia-reperfusion (I/R) injury in rats. Methods Thirty male Wistar rats weighing 300-350 g were randomly divided into 3 groups ( n = 10 each): group I sham operation (group S); group II I/R and group Ⅲ HH. Partial liver ischemia was produced by clamping hepatic portal vein and left arteria hepatica for 30 min with atraumatic mini-clamp, followed by 2 h of reperfusion in I/R group and HH group. In HH group the animals were infused hypertonic saline plus hetastarch solution 40 injectio 10 ml/kg through vena caudalis over 30 min and then hepatic I/R was performed IS min after the infusion.The animals were killed at 2 h of reperfusion. The left liver was removed and blood sample was taken from inferior caval vein for determination of (1) serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities; (2) superoxide dismutase ( SOD) activity and malondialdehyde ( MDA) content in the liver; ( 3 ) microscopic examination. Results The serum ALT and AST activities and MDA content in the liver were significantly higher, SOD activity in the liver significantly lower after hepatic I/R and pathological changes in the liver severer in group I/R and HH than in group S. The serum ALT and AST activities and MDA content in the liver were significantly lower, SOD activity in the liver significantly higher after hepatic I/R and pathological changes in the liver milder in group HH than in group I/R. Conclusion Hypervolemic hemodilution with hypertonic saline plus hetastarch solution 40 injectio can ameliorate hepatic I/R injury by decreasing oxygen free radical production in rats.     

结构脂肪乳与中/长链脂肪乳对危重症患者肝功能和血脂的影响比较

目的：探讨结构脂肪乳及中/长链脂肪乳对危重症患者肝功能和血脂的影响。方法采用随机法将98例患者分为两组，即MCT/LCT组与STG组，两组均为49例，两组所患疾病、APACHE II评分、年龄及性别等均无显著性差异（P＞0.05），具有可比性。患者进入ICU后，立即对身体状况及病情进行评估，确定不存在肠外营养支持方面的禁忌证后采用MCT/LCT及STG进行治疗。在第1～2天静脉输注葡萄糖，第3天后开始实施肠外营养支持治疗，两组均连续治疗15d。结果采用两种不同的脂肪乳进行治疗后，两组的AST、TG及TCH、LDL-C差异有统计学意义（P＜0.05），MCT/LCT组的AST、TG、TCH及LDL-C值大于STG组。在HDL-C、DBIL、TBIL、ALP、及ALT方面，治疗前后两组的差异均不明显（P＞0.05）。结论在为危重症患者提供营养支持时，STG对血脂及肝功能各项指标的影响较小，应推广使用STG。     

含不同脂肪乳剂的肠外营养对肝移植大鼠肝脏功能的影响

目的　研究含不同脂肪乳剂的肠外营养 (TPN)对肝移植大鼠肝脏功能的影响。方法　建立肝移植大鼠模型 ,按照提供的能源不同分为单糖 (GLU )、脂肪乳剂MCT/LCT、LCT、STG 4个组 ,实验期为 7d ,记录实验期内动物死亡情况 ,于TPN后第 1、4、7d收集标本 ,检测AKBR(动脉血酮体比值 )、血ALT、AST、血TBIL。以正常和肝移植大鼠作为对照。结果　单糖组 7d动物死亡率显著高于脂肪乳剂组 (5 0 %vs0 % )。与脂肪乳组相比 ,单糖组动物 7d内血清ALT和AST水平降低缓慢、TBIL水平持续显著升高 ,AKBR水平在TPN后 1d恢复并稳定于较高水平 ,但于 7d时显著降低。在 1、4d时STG组动物血清ALT降低较MCT/LCTTPN组及LCTTPN组更为显著 ,MCT/LCTTPN组血清ALT水平低于LCTTPN组。结论　单糖TPN加重移植肝脏功能损害 ,动物死亡率增高 ,含脂肪乳的TPN能促进移植肝功能恢复。在减轻移植肝功能损害方面的优越性 ,依次为STG、MCT/LCT和LCT。     

实验性肝移植中透明质酸的变化

目的 通过实验性猪背驮式肝移植手术,观察肝移植手术过程中不同时期受体猪外周血液中透明质酸的变化,以及供体肝脏植入、血流再通、温血再灌注后受体的外周血液中透明质酸变化,并探讨这些变化在肝移植手术中的意义。方法 健康种猪15对,分别抽取手术前、无肝期前、无肝期、新肝期各时点的外周静脉血,经放射兔疫分析法检测透明质酸浓度。结果 手术平均时间(343.33±73.99)min,其中麻醉后至手术开始平均时间为(8.34±21.56)min,收缩压平均下降(23.51±5.87)mm Hg,舒张压平均下降(11.35±7.81)mm Hg,手术开始至无肝期前平均时间为(146.13±41.61)min,无肝期平均时间为(47.07±25.35)min。手术前透明质酸达到267μg/L,无肝期前上升到1743μg/L(P<0.05),无肝期内外周血透明质酸浓度急剧上升,达到9530μg/L,明显较其余各时点高(P<0.01),供体肝脏植入重新开放血流后外周血透明质酸浓度下降至1485μg/L,其变化与ALT和AST有较好的相关性(分别r=0.674 P=0.000和r=0.509 P=0.008)。结论 麻醉过程、麻醉药物以及肝移植手术中各种因素都可以引起外周血液中透明质酸浓度的增高。供体肝脏经过冷灌注保养和温血再灌注后受体的外周血液透明质酸浓度明显增高,并与肝功能的变化有一定的相关性。     

肝移植术后早期脂肪乳剂支持治疗对移植肝功能影响的临床研究

目的　研究含脂肪乳剂的肠外营养 (TPN)对肝移植受体肝脏功能的影响。方法　选择2 0 0 1年 9月～ 2 0 0 4年 6月期间在我所肝移植中心住院行肝移植手术治疗的患者 ,取符合标准的 30例作为研究对象 ,随机分组 ,进行前瞻性的临床研究。肝移植术后 6h开始给予单糖或脂肪乳剂和单糖联合功能的TPN(分别为Glu对照组和MCT/LCT组 ) ,TPN期为 7d ,期间严格禁食。于TPN后第 1、4、7、10、30、90及 180天收集标本 ,检测血ALT、AST、GGT、TBil及DBil。结果　TPN支持后MCT/LCT和Glu组ALT、AST、GGT、TBil及DBil水平均呈现下降趋势 ,与单糖组相比 ,脂肪乳组降低迅速。结论　含脂肪乳的TPN较单糖TPN更有利于促进移植肝早期功能恢复     

The injection pain of propofol with different emulsion

BACKGROUND: Incidence and intensity of pain on intravenous injection of propofol were assessed with emulsion of long-chain/medium-chain triglycerides (LCT/MCT, 50: 50) and only long-chain triglycerides (LCT, 100) in patients undergoing different elective surgical interventions in this prospective, randomized, cross over and double-blinded study. METHODS: 1) Forty six patients were assigned to two groups. One group received 0.2 mg x kg(-1) LCT/ MCT propofol prior to LCT propofol administration. The other group received 0.2 mg x kg(-1) LCT propofol prior to LCT/MCT propofol administration. Pain elicited upon questioning was assessed with each injection in the two groups. Patients were asked to grade the pain as VAS of 0 to 100 mm. 2) Fifty one patients were randomly assigned to two groups. One group received 0.4 mg x kg(-1) LCT propofol. The other group received 0.4 mg x kg(-1) LCT/MCT propofol. Patients were asked to grade the pain as VAS of 0 to 100 mm. RESULTS: Pain of LCT propofol injection was stronger than LCT/MCT propofol. As incidence of 0.4 mg x kg(-1) propofol injection, VAS on LCT/MCT propofol and LCT propofol gave score as 0 and 23.5 (P=0.0019). CONCLUSIONS: Propofol with emulsion of long- and medium-chain triglycerides appears to reduce the injection pain than with emulsion of only long-chain triglycerides.     

中、长链脂肪乳剂对肝硬变家兔胆红素代谢及肝功能的影响

研究长链脂肪乳剂和中/长链混合脂肪乳剂二种不同肠外营养液支持下,观察血中游离脂肪酸浓度变化对胆红素和肝功能的影响。方法:21只新西兰大白兔经结扎胆总管制成胆源性肝硬化动物模型,随机分为三组:正常对照组(n=6);肝硬化肠外营养PN-LCT组(n=10);肝硬化肠外营养PN-MCT/LCT组(n=11)。两组的PN液所含热量及氮量均相等。在PN的第1、7天,用高效液相色谱(HPLC)测定PN后4h血中游离脂肪酸(FFA)浓度,并常规测定胆红素及白蛋白和肝脏酶学的变化。结果:肝硬变形成后,总胆红素及直接胆红素、丙氨酸转氨酶(ALT)、天门东氨酸转氨酶、碱性磷酸酶、γ-谷酰转肽酶均明显升高,而白蛋白明显下降,P<0.01。PN期间,FFA及FFA/白蛋白比值也明显升高,P<0.01。PN第7天时,LCT组直接胆红素及ALT和FFA/白蛋白比值均明显高于MCT/LCT组,P<0.01。结论:MCT/LCT乳剂可能是应用于肝硬变兔更为理想的能量来源。     

Mechanism of injection pain with long and longmedium chain triglyceride emulsive propofol

PURPOSE: t has been suggested that long-medium chain triglyceride (LCT/MCT) emulsive propofol causes less injection pain than long chain triglyceride (LCT) emulsive propofol because of the decreased propofol concentration in the aqueous phase. Alternatively, LCT propofol generates bradykinin causing the injection pain and activates complement, but these effects when using LCT/MCT propofol have not been examined. To identify the mechanism for reduced pain with LCT/MCT propofol, injection pain, bradykinin generation and complement activation with use of both propofol products were compared. METHODS: Two hundred adult patients randomly allocated to two groups were given 1.5 mg x kg(-1) iv of either LCT propofol or LCT/MCT propofol at a rate of 200 mg x min(-1) in a double-blind manner and were asked to grade pain scores. In another study, bradykinin and activated complement 3 (C3a) concentrations were measured using blood obtained from 13 healthy volunteers mixed with saline, LCT propofol or LCT/MCT propofol. RESULTS: There was a significant difference in pain scores between groups, showing a lower incidence of injection pain in the LCT/MCT propofol group. The bradykinin concentrations in blood mixed with LCT and LCT/MCT propofol were significantly higher than in blood mixed with saline. The C3a concentrations showed similar results. CONCLUSIONS: LCT/MCT propofol causes less pain on injection compared with LCT propofol. Bradykinin generation and complement activation are similar with both LCT and LCT/MCT propofol. Thus, the reason for less pain on injection with LCT/MCT propofol may be attributed to a decreased concentration of propofol in the aqueous phase.     

Evaluation of low-dose propofol preadministration to attenuate vascular pain during induction of anesthesia

STUDY OBJECTIVE: To determine whether a small dose of propofol before induction decreases pain with injection using two different formulas of propofol-10% long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) and LCT. DESIGN: Prospective, randomized, comparative study. SETTING: University-affiliated hospital. PATIENTS: 200 ASA physical status I and II patients. INTERVENTIONS: Group A (LCT control) and group B (MCT/LCT control) were first preadministered normal saline plus Intralipid (Otsuka Pharmaceutical Co, Ltd, Tokyo, Japan) as a placebo, whereas group C (LCT study) and group D (MCT/LCT study) received each formulation of propofol 0.1 mg/kg before induction. After three minutes, groups A and C received LCT propofol two mg/kg for induction. Groups B and D received LCT/MCT propofol in the same manner. MEASUREMENT: Pain was evaluated blindly at the time of both preadministration and induction, using a 4-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, and 3 = severe pain. MAIN RESULTS: 36 (72%) LCT and 31 (62%) LCT/MCT control group patients (groups A and B) had pain. Pretreatment with propofol (groups C and D) attenuated the frequency of pain significantly in 21 (42%) and 24 (48%) patients at induction, respectively. CONCLUSION: Long-chain triglyceride and LCT/MCT propofol, 0.1 mg/kg administration before induction, resulted in attenuated pain at an induction dose of propofol.     

异丙酚对腹腔镜胆囊切除术气腹患者肝功能的影响

目的 评价异丙酚对腹腔镜胆囊切除术气腹患者肝功能的影响.方法 择期行腹腔镜胆囊切除术患者50例,ASA Ⅰ或Ⅱ级,年龄18～64岁,随机分为2组(n=25):异氟醚组(Ⅰ组)和异丙酚组(P组).麻醉诱导:静脉注射芬太尼3 gg/kg、依托咪酯0.3 mg/kg和琥珀胆碱1 mg/kg,气管插管后机械通气;麻醉维持:两组均静脉注射维库溴铵1～1.2 mg/kg,每30分钟静脉注射芬太尼1～2 μg/kg和维库溴铵0.5 mg/kg,Ⅰ组吸入异氟醚1.3 MAC,P组靶控输注异丙酚(血浆靶浓度2.0～2.3μg/ml).于麻醉诱导前(T0)和气腹解除后5 min(T1)时抽取肘静脉血样4 ml,检测血浆丙二醛(MDA)浓度、超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH-PX)活性和总抗氧化能力(T-AOC).于T0及术后24 h(T2)时抽取肘静脉血样2 ml,检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)活性和总胆红素(T-BIL)浓度.结果 与T0时比较,两组T1时血浆MDA浓度升高,SOD、GSH-PX活性和T-AOC降低,T2时血清ALT、AST、T-BIL水平升高(P＜0.05或0.01);与Ⅰ组比较,P组血浆MDA浓度降低,SOD、GSH-PX活性和T-AOC升高,血清ALT、AST和T-BIL水平降低(P＜0.05).结论 腹腔镜胆囊切除术中靶控输注异丙酚(血浆靶浓度2.0～2.3μg/ml)可减轻CO2气腹诱发肝功能损害,有利于术后早期肝功能的恢复,其机制可能与减轻脂质过氧化反应有关.     

胆源性肝硬变家兔肝脏脂蛋白脂酶变化对脂代谢的影响

目的:观察肝硬变家兔肝脏脂蛋白脂酶(LPL)变化对脂代谢的影响。方法:21只新西兰大白兔制成胆源性肝硬变模型后,随机分为长链脂肪乳剂(LCT)-肠外营养(PN)组(LCT组,n=10)和中/长链混合乳剂(MCT/LCT)-PN组(MCT组,n=11),另设正常对照组(n=12)。肠外营养(PN)前、PN后1、4、7d分别测定血浆甘油三酯(TG)和胆固醇(Chol)。实验结束后处死动物,取肝脏作病理形态学检查以及脂肪含量测定,用ABC法作LPL单克隆抗体在肝脏的表达;用Northern杂交法检测LPL基因的mRNA表达。结果:MCT乳剂对甘油三酯及胆固醇代谢的影响较小,MCT组的肝脏脂肪含量明显低于LCT组,P<0.01。形态学检查表明,两组的变性、坏死和增生性病变的检出率均无显著差异,但在LCT组肝细胞中能较多地见到脂肪颗粒。肝脏二氨基联苯胺(DAB)显色以及mRNA表达明显下降。结论:肝硬化时,肝脏代谢脂肪的能力已受损;相对而言,此时对MCT乳剂的体内代谢较小影响。