血红素氧化酶-1介导脂联素在脓毒症肺损伤中的保护作用

目的 探讨血红素氧化酶-1(heme oxygenase,HO-1)介导脂联素(adiponectin,APN)在脓毒症肺损伤中的保护作用.方法 80只雄性Wistar大鼠采用随机数字表法分为4组(每组20只):对照组(C组)、脓毒症模型组(LPS组)、脂联素预处理组(APN组)和HO-1抑制剂锌原卟啉IX(zinc protoporphyrin IX,ZnPP IX)干预组(Zn组).各组分别于腹腔注射脂多糖(lipopolysaccharide,LPS) (20 mg/kg)或0.9％氯化钠溶液后6h,采用酶联免疫吸附法检测血清中肿瘤坏死因子(tumor necrosis factor-alpha,TNF-α)和白介素(interlukin-6,IL-6)的含量.采用分光光度法测定一氧化氮(nitric oxide,NO)浓度、肺组织丙二醛(malonaldehyde,MDA)和髓过氧化物酶(myeloperoxidase,MPO)活性变化.采用实时荧光定量聚合酶链反应(real-time PCR)法检测肺组织HO-1、诱导型一氧化氮合成酶(inducible nitric oxide synthase,iNOS)mRNA的表达水平.观察5d内大鼠生存情况,并绘制生存曲线. 结果 与C组比较,LPS组、APN组和Zn组血清TNF-α [(321.3±11.2)、(132.5±10.2)、(311.7±12.4)vs (52.1±1.4)] ng/L、IL-6[(2 229.26±210.25)、(1 134.14±11.24)、(2 028.27±167.04)vs(55.38±0.23)] ng/L、NO[(103±10)、(79±8)、(97±9)vs(48±3)] μmol/L和肺组织匀浆MDA[(16.209±0.151) 、(5.943±0.310)、(13.238±0.326)vs(3.081 ±0.017)] μmol/g、MPO[(12.42±0.46)、(6.77±0.14)、(10.45±0.21)vs(2.74±0.06)] U/g水平显著升高(P＜0.05),生存率显著下降(20％ vs 100％;70％ vs 100％;30％ vs 100％,P＜0.05);与LPS组比较,APN组血清TNF-α [(132.5±10.2)vs (321.3±11.2)] ng/L、IL-6 [(1 134.14±107.13)vs(2229.26±210.25)] ng/L、NO[(79±8)vs (103±10)] μmol/L和肺组织匀浆MDA[(5.943±0.310)vs (16.209±0.151)] μmol/g、MPO [(6.77±0.14)vs (12.42±0.46)] U/g水平显著降低(P＜0.05),肺组织HO-1 mRNA[(8.73±0.24)vs(1.54±0.03)]显著升高(P＜0.05),iNOS mRNA[(1.42±0.15)vs(2.01±0.10)]显著下降(P＜0.05),生存率显著增高(70％ vs 20％,P＜0.05);与APN组比较,Zn组血清TNF-α[(311.7±12.4)vs(132.5±10.2)] ng/L、IL-6[(2 028.27±167.04)vs(1 134.14±107.13)]ng/L、NO[(97±9)vs(79±8)] μmol/L和肺组织匀浆MDA[(13.238±0.326)vs(5.943±0.310)] μmol/g、MPO[(10.45±0.21)vs(6.77±0.14)] U/g水平显著升高(P＜0.05),肺组织HO-1 mRNA[(2.66±0.14)vs (8.73±0.24)]显著下降(P＜0.05),iNOS mRNA[(2.06±0.23)vs(1.42±0.15)]显著升高(P＜0.05),生存率显著下降(30％ vs 70％,P＜0.05). 结论 HO-1可能介导了APN在脓毒症性肺损伤中的保护作用.     

脂联素预先给药对内毒素血症大鼠肝损伤的影响

目的 评价脂联素预先给药对内毒素血症大鼠肝损伤的影响.方法 雄性Wistar大鼠80只,10～ 14周龄,体重250 ～ 300 g,采用随机数字表法,将其分为4组(n=20):对照组(C组)、内毒素血症组(LPS组)、脂联素预先给药组(APN组)和白细胞介素-10(IL-10)中和抗体干预组(IL-10抗体组).LPS组、APN组和IL-10抗体组腹腔注射脂多糖(LPS)20 mg/kg,APN组和IL-10抗体组于给予LPS前12 h腹腔注射基因重组脂联素6 mg/kg,IL-10抗体组于给予基因重组脂联素前30 min腹腔注射IL-10中和抗体3 mg.每组于注射LPS后2h时取10只大鼠,采集心脏全血,检测血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-10(IL-10)水平;每组于注射LPS后2h另取10只大鼠,取肝组织,检测丙二醛(MDA)含量、髓过氧化物酶(MPO)活性、IL-10 mRNA以及血红素氧化酶-1(HO-1) mRNA表达.结果 与C组比较,LPS组、APN组和IL-10抗体组血清AST、ALT及TNF-α、IL-1β、IL-10水平、肝组织MDA含量和MPO活性升高,肝组织HO-1 mRNA表达上调,LPS组和APN组IL-10 mRNA表达上调(P＜0.05);与LPS组比较,APN组和IL-10抗体组血清AST、ALT及TNF-α 、IL-1β水平、肝组织MDA含量和MPO活性降低,肝组织HO-l mRNA表达上调,APN组肝组织IL-10 mRNA表达上调(P＜0.05);与APN组比较,IL-10抗体组血清AST、ALT及TNF-α、IL-1β水平、肝组织MDA含量和MPO活性升高,血清IL-10浓度降低,肝组织HO-1 mRNA表达下调(P＜0.05).结论 脂联素预先给药可减轻内毒素血症大鼠肝损伤,其机制与诱导IL-10生成有关.     

高迁移率族蛋白1参与脓毒症大鼠急性呼吸窘迫综合征时中性粒细胞的凋亡

目的 探究脓毒症大鼠急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)时高迁移率族蛋白1(high mobility group box 1,HMGB1)参与中性粒细胞(polymorphonuclear neutrophils,PMN)凋亡延迟的相关机制及正丁酸钠(sodium butyrate,SB)的干预效果. 方法 采用随机数字表法将90只健康成年雄性Sprague-Dawley(SD)大鼠随机分为正常对照组(NS组,6只)、内毒素(lipopolysaccharide,LPS)致伤组(LPS组,42只)、HMGB1抑制剂SB干预组(SB组,42只),LPS组、SB组又分为7个时相点(LPS致伤后0.5、1、2、6、12、24、48 h),每个时相点6只动物.LPS组,腹腔注射LPS 5 mg/kg;SB组,腹腔注射LPS 5 mg/kg后0.5 h静脉注射SB,每次剂量500 mg/kg;NS组,腹腔注射生理盐水1 ml.LPS组、SB组于LPS注射后各时点,颈静脉取血检查PMN,取血后左肺灌洗收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),取右肺中叶行HMGB1 mRNA检测;于LPS注射12h时点(NS组大鼠留取颈静脉血、收集BALF、取右肺中叶行HMGB1 mRNA检测),3组大鼠收集左肺BALF后,取右肺下叶检测肺组织湿/干重比(wet/dry weight ratio,W/D),取右肺上叶进行病理组织学检查;于24、48 h时点,LPS组、SB组取右肺下叶检测肺组织W/D、取右肺上叶进行病理组织学检查. 结果 与NS组比较,LPS组肺组织中HMGB1 mRNA表达量明显增高,24 h达最大值,差异有统计学意义(P＜0.05);SB组的HMGB1 mRNA表达量减少,差异有统计学意义(P＜0.05).LPS组BALF中凋亡早期PMN表达量与NS组类似,但凋亡晚期PMN变化则不同,LPS组外周血中凋亡晚期PMN细胞高于NS组(P＜0.05),LPS组BALF中凋亡晚期PMN细胞均低于NS组(P＜0.05).LPS 12 h组BALF的PMN百分比明显高于NS组[(49.1±6.8)、(2.7±0.5)],差异有统计学意义(P＜0.01).LPS组肺组织光镜下可见肺泡腔水肿,支气管壁中发现PMN浸润,肺泡壁毛细血管扩充血.LPS24 h组肺组织的W/D明显高于NS组[(6.71±0.12)、(4.18±0.26)],差异有统计学意义(P＜0.05).SB干预组的HMGB1 mRNA表达量减少,早期凋亡率类似,SB组的BALF晚期凋亡率高于同时点LPS组的BALF,SB外周血组晚期凋亡低于同时点LPS外周血组,差异有统计学意义(P＜0.05).SB组BALF的PMN百分比、肺组织病理损伤程度、W/D均低于LPS组,差异有统计学意义(P＜0.05). 结论 在大鼠ARDS中,HMGB1 mRNA表达较晚,但持续时间长,SB对HMGB1有潜在的治疗作用,HMGB1可能参与PMN凋亡机制的调节.     

不同剂量6%羟乙基淀粉130/0.4预先给药对大鼠内毒素性急性肺损伤的影响

目的 研究不同剂量6%羟乙基淀粉130/0.4(6% HES 130/0.4)预先给药对大鼠内毒素性急性肺损伤的影响.方法 72只健康清洁级雄性SD大鼠随机分为6组(n=12),对照组(C组)经尾静脉注射生理盐水30 ml/kg;肺损伤组(L组)经尾静脉注射脂多糖(LPS)5 mg/kg;不同剂量6%HES130/0.4组分别经尾静脉注射6%HES 130/0.4 7.5 ml/kg(H1组)、15 ml/kg(H2组)和30 ml/kg(H3组),1 h后再经尾静脉注射LPS 5 mg/kg;H4组经尾静脉注射6%HES 130/0.4 30 ml/kg.各组给药速率均为0.2ml/min.注射LPS后4 h行动脉血气分析,气管插管.每组取6只大鼠,测定肺组织微血管通透性指数(PMPI);每组取6只大鼠,测定支气管肺泡灌洗液(BALF)蛋白浓度、肺组织湿/干重比(W/D)、髓过氧化物酶(MPO)活性,血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)、丙二醛(MDA)浓度和超氧化物歧化酶(SOD)活性,观察肺组织病理学.结果 与L组比较,H2组血清TNF-α、IL-1β、MDA浓度和肺组织MPO活性降低,血清IL-10浓度和SOD活性升高,H1组IL-1β浓度降低,H1组、H2组和H3组PMPI、BALF蛋白浓度和W/D均降低(P＜0.05);与H2组比较,H1组和H3组血清TNF-α、MDA浓度和肺组织MPO活性升高,血清SOD活性、IL-10浓度降低,H3组血清IL-1β浓度升高(P＜0.05).H1组、H2组和H3组较L组肺组织损伤较轻,其中H2组损伤最轻.结论 15 ml/kg6%HES 130/0.4预先给药可减轻大鼠内毒素性急性肺损伤,其机制可能与抑制炎性因子释放、减少肺内中性粒细胞聚集和氧自由基生成、改善肺微血管通透性有关.     

阿司匹林诱生型脂氧素A4对脂多糖诱导小鼠急性肺损伤的影响

目的 评价阿司匹林诱生型脂氧素A4 (ATL)对脂多糖(LPS)诱导小鼠急性肺损伤的影响.方法 雄性SPF级BALB/C小鼠30只,体重25～30 g,10～ 12周龄,采用随机数字表法,将其分为3组(n=10):对照组(NS组)气管内滴定生理盐水(LPS溶媒)1.5 ml/kg,1h后尾静脉注射50％无水乙醇(ATL溶媒)0.1 ml; LPS组气管内滴定LPS 3 mg/kg,1h后尾静脉注射50％无水乙醇0.1 ml; ATL组气管内滴定LPS 3 mg/kg,1h后尾静脉注射ATL 0.2 mg/kg.气管内滴定药物后24h处死,采集支气管肺泡灌洗液(BALF),计数总细胞数、多形核粒细胞比例、单个核细胞比例及其总蛋白、TNF-α、IL-6、单核细胞趋化蛋白-1(MCP-1)、IL-10的浓度;取肺组织,测定髓过氧化物酶(MPO)活性、p38丝裂原活化蛋白激酶(p38 MAPK)、c-Jun氨基末端激酶(JNK)、细胞外调节蛋白激酶(ERK1/2)的磷酸化水平,并观察肺组织病理学结果,行肺损伤评分.结果 与NS组比较,LPS组和ATL组肺损伤评分、BALF中总细胞数、多形核粒细胞比例、TNF-α、IL-6、MCP-1浓度升高,单个核粒细胞比例降低,LPS组BALF中IL-10浓度降低,总蛋白浓度、肺组织MPO活性、p38 MAPK、JNK、ERK1/2的磷酸化水平升高(P＜0.05),ATL组BALF中总蛋白、IL-10浓度、肺组织MPO活性、p38 MAPK、JNK、ERK1/2的磷酸化水平差异无统计学意义(P＞0.05);与LPS组比较,ATL组肺损伤评分、BALF中总细胞数、多形核粒细胞比例和总蛋白、TNF-α、IL-6、MCP-1浓度降低,单个核粒细胞比例和IL-10浓度升高,肺组织MPO活性、p38MAPK和JNK的磷酸化水平降低(P＜0.05),ERK1/2的磷酸化水平差异无统计学意义(P＞0.05).结论 ATL可减轻LPS诱导的小鼠急性肺损伤,其机制与抑制p38 MAPK和JNK信号通路激活有关.     

肺组织γ-氨基丁酸A型受体在大鼠内毒素诱发急性肺损伤中的作用

目的 探讨肺组织γ-氨基丁酸A型受体(GABAAR)在大鼠内毒素诱发急性肺损伤中的作用.方法 成年健康雄性Wistar大鼠32只,8周龄,体重200 ～ 230 g,采用随机数字表法,将其随机分为4组(n=8)∶正常对照组(C组)、内毒素组(LPS组)、γ-氨基丁酸预先给药+内毒素组(GABA组)和GABAAR拮抗剂荷包牡丹碱预先给药+内毒素组(BIC组).LPS组、GABA组和BIC组尾静脉注射LPS 5 mg/kg,C组给予等容量生理盐水;GABA组和BIC组分别于给予LPS前30 min时腹腔注射γ-氨基丁酸50 mg/kg和荷包牡丹碱10 μmol/kg.于给予LPS后6h时,采集动脉血样,测定PaO2,然后取肺组织,测定肺湿/干重比(W/D)、GABAAR表达、IL-6、TNF-α、MDA的含量和SOD活性,光镜下观察肺组织病理学结果.结果 与C组比较,LPS组、GABA组和BIC组PaO2降低,LPS组和GABA组肺组织W/D、TNF-α、IL-6和MDA的含量升高,肺组织GABAAR表达上调,肺组织SOD活性降低(P＜0.05);与LPS组比较,GABA组肺组织W/D、TNF-α、IL-6和MDA的含量升高,肺组织GABAAR表达上调,肺组织SOD活性降低(P＜0.05),而BIC组上述指标差异无统计学意义,GABA组和BIC组PaO2差异无统计学意义(P＞0.05).结论 肺组织GABAAR参与了大鼠内毒素诱发急性肺损伤的发展.     

氯胺酮复合乌司他丁对大鼠内毒素性急性肺损伤的影响

目的 探讨氯胺酮复合乌司他丁对大鼠内毒素性急性肺损伤(acute lung injury,ALI)的影响.方法 成年雄性SD大鼠100只,体重280 g～320 g,采用计算机简单随机分组法随机分为5组(每组20只):对照组(C组)、内毒素组(L组)、氯胺酮组(K组)、乌斯他丁组(U组)、氯胺酮复合乌斯他丁组(K+U组).除C组外,其余大鼠腹腔注射0.03％脂多糖(lipopolysaccharide,LPS)1 mg/kg,注射后16 h时,由尾静脉再次注射0.1％ LPS 1.5 mg/kg,建立大鼠ALI模型.U组、K+U组分别在第2次注射LPS后经尾静脉注射乌司他丁50 000 U/kg,注射乌司他丁后即刻,K组、K+U组经尾静脉以微量泵持续输注氯胺酮10 mg·kg-1·h-1,其余组注射等容量生理盐水.于第2次注射LPS后1、2、3、4h(T1-4)时,各组取5只大鼠,抽取腹主动脉血样0.5 ml,测定氧分压(PaO2),抽取下腔静脉血样2 ml,测定血清肿瘤坏死因子(tumor necrosis factor,TNF)-α和白介素(interleukin,IL)-6浓度;放血处死大鼠,取右肺上叶组织,光镜下观察肺组织病理学结果,进行肺组织病理半定量评分及测定核因子(nuclear factor-κB,NF-κB)抑制蛋白α(inhibitor of nuclear factor κBα,IκBα)表达;取右肺中叶组织100 mg测定肺组织NF-κB活性;取右肺下叶组织,计算肺湿干重比(W/D).结果 与C组比较,L组、K组、U组和K+U组PaO2降低,血清TNF-α、IL-6浓度和肺组织NF-κB活性升高,IκBα表达降低,W/D升高(P＜0.01);与L组比较,K组、U组和K+U组PaO2升高,血清TNF-α、IL-6浓度和肺组织NF-κB活性降低,IκBα表达升高,W/D降低,肺组织病理评分降低(P＜0.05或0.01);与K组和U组比较,K+U组各时点PaO2升高,血清TNF-α、IL-6浓度和肺组织NF-κB活性(2.49±0.23)降低,IκBα表达(35.1±3.4)升高,W/D(4.91±0.16)降低,肺组织病理评分(7.8±0.8)降低(P＜0.05或0.01).结论 氯胺酮复合乌司他丁可减轻大鼠ALI,较两者单独应用效果显著.     

丙泊酚和依托咪酯对脓毒症小鼠炎症反应与氧化应激的影响

目的观察丙泊酚及依托咪酯对脓毒症小鼠炎症反应与氧化应激的影响。方法雄性成年BALB/c小鼠64只,随机分为四组(n=16):正常对照组(N组)、脓毒症组(S组)、丙泊酚处理组(P组)及依托咪酯处理组(E组)。脂多糖(LPS,20mg/kg)腹腔注射建立脓毒症模型,丙泊酚(60mg/kg)或依托咪酯(10mg/kg)于LPS注射后0.5h腹腔注射给药。于LPS注射后2h及6h检测血清IL-6、IL-10浓度,6h检测肺、肝、肾组织中的丙二醛(MDA)含量。结果与N组比较,S组2h及6h血清IL-6浓度明显上升(P0.05),IL-10浓度明显下降(P0.05);6h肺、肝、肾组织MDA含量均明显上升(P0.05)。与S组比较,P、E两组2h及6h血清IL-6浓度均明显下降(P0.05),IL-10浓度均明显上升(P0.05);E组6h肺、肝、肾组织MDA含量明显下降(P0.05),P组6h仅肺组织MDA含量明显下降(P0.05)。E组2h血清IL-6浓度明显低于P组(P0.05),2h及6h血清IL-10浓度明显高于P组(P0.05);6h肺、肝、肾组织MDA含量均明显低于P组(P0.05)。结论丙泊酚和依托咪酯腹腔注射均可减轻LPS所致脓毒症小鼠炎症反应及氧化应激损伤,且依托咪酯的作用更强。     

白细胞介素-10通过降低脂多糖诱导大鼠急性肺损伤高迁移率组蛋白1释放产生保护作用

目的 旨在研究白细胞介素（interleukin,IL）-10对高迁移率组蛋白l（high mobility group protein 1,HMGB1）释放的影响及其肺保护作用,进而探讨IL-10在治疗急性肺损伤中的可能机制. 方法 采用腹腔注射脂多糖（lipopolysaccharide,LPS）致大鼠脓毒症急性肺损伤模型,健康SPF级雄性SD大鼠72只,体重180 g～220 g,采用随机数字表法,随机分为对照组即磷酸盐缓冲液（phosphate buffered solution,PBS）组（P组,6只）、急性肺损伤组即LPS组（L组,30只）、PBS＋IL-10组（PI组,6只）、LPS＋IL-10组（LI组,30只）.P组和PI组腹腔注射等体积PBS的同时分别经由气道滴注5 ml的PBS和IL-10,L组和LI组腹腔注射LPS的同时分别经由气道滴注等体积的PBS和IL-10.L组和LI组注射LPS后的4、8、16、24 h和48 h分别检测各组大鼠肺湿/干重比（wet/dry weight ratio,W/D）和支气管肺泡灌洗液（bronchoalveolar lavage fluid,BALF）中总蛋白浓度,酶联免疫吸附实验法检测BALF中炎性因子肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）和IL-6水平,苏木精-伊红（hematoxylin-eosin,HE）染色观察肺组织的病理变化,Western Blot分析肺组织中HMGB1表达水平. 结果 腹腔注射LPS后,L组大鼠肺组织W/D和BALF中总蛋白浓度分别为（5.68±0.12） mg/L和（254±105） mg/L,与P组比较,分别增加了12％和297％（P＜0.05）,BALF中TNF-α和IL-6水平明显增加（P＜0.05）,HE染色显示在注射LPS后4h肺组织的细胞浸润达到峰值随后减少,肺组织中HMGB1水平升高（P＜0.05）;使用IL-10后,LI组肺组织W/D和BALF中总蛋白浓度分别为（5.28±0.14） mg/L和（109±48） mg/L,与L组比较,分别降低了7％和57％ （P＜0.05）,BALF中炎性因子水平降低（P＜0.05）,肺组织细胞浸润改善,HMGB1表达下调（P＜0.05）. 结论 IL-10对急性肺损伤具有保护作用,其机制可能为降低BALF中炎性因子的水平,下调晚期炎症介质HMGB1的表达,从而改善肺组织的细胞?     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.