一氧化氮合成酶在大鼠小肠移植急性排斥反应中的作用

目的 观察神经型(nNOS)和诱导型一氧化氮合成酶(iNOS)在大鼠小肠移植急性排斥反应(AR)中作用.方法 行大鼠原位小肠移植.实验分为2组.1组:同系移植组(Lewis→Lewis,12例);2组:同种移植组(DA→Lewis,12例).观察术后生存时间.再灌注30 min、术后1、3、5、7d检测血清一氧化氮(NO)浓度;开腹行麦芽糖吸收实验;切取移植肠管,苏木素-伊红(HE)染色后光镜检查.免疫组织化学法观察移植肠nNOS和iNOS的活性.逆转录-聚合酶链反应(RT-PCR)法检测移植肠nNOS mRNA和iNOS mRNA的表达.结果 A组生存时间＞30 d.B组生存时间为(6.83±0.75)d.再灌注后A组nNOS染色与mRNA表达明显减弱,此后nNOS染色和mRNA表达分别于术后3、7d恢复正常.再灌注后A组iNOS染色与mRNA表达增强,此后逐渐减弱.与A组比较,术后3～7 d,B组nNOS染色减弱,iNOS染色增强,血清NO水平明显升高(P＜0.05),血糖吸收值显著降低(P＜0.01);术后5、7d,B组nNOS mRNA表达显著下降(P＜0.001),iNOS mRNA表达明显增强(P＜0.01).结论 在AR过程中,nNOS可能调节了iNOS的表达;nNOS的活性和表达与移植肠管的结构和吸收功能密切相关;iNOS的激活是加重组织损伤的重要因素之一.     

环孢素A与他克莫司对大鼠原位小肠移植慢性排斥反应的影响

目的 建立稳定可靠的长期存活大鼠原位小肠移植慢性排斥反应(CR)模型,比较环孢素A(CsA)与他克莫司(Tac)诱导的CR的特点.方法 供、受鼠分别为雄性近交系F344、Lewis大鼠,移植小肠肠系膜上动脉、门静脉分别与受鼠肾下腹主动脉及下腔静脉端侧吻合,切除受鼠原小肠,移植小肠两端分别与受鼠肠行端端吻合.研究Ⅰ为受鼠手术当天至术后第13天肌肉注射CsA,5mg·kg-1 ·d-1.研究Ⅱ为手术当天至术后第13天及术后第20、27天肌肉注射Tac,低、中、高剂量组的剂量分别为0.3、0.5、1.0 mg·kg-1 ·d-1.观察大鼠存活率、体重及组织形态学改变.结果 研究Ⅰ中,受鼠术后60、90 d的病理表现均为CR,但肠黏膜钝化不明显.研究Ⅱ中,低、中剂量组受鼠最长存活126 d,而高剂量组受鼠存活超过180 d,体重增长曲线接近同系移植组.CsA与Tac制备的受鼠移植小肠病理学表现均为中、重度CR,但Tac制备的模型更接近临床小肠移植的CR病理学特征.结论 以F344大鼠为供鼠、Lewis大鼠为受鼠,分别以CsA、Tac为免疫抑制剂均可建立稳定的大鼠原位小肠移植CR模型,Tac制备的受鼠存活时间更长,病理学特征更为典型.     

低分子肝素减轻大鼠移植心脏排斥反应的作用及其机制

目的 探讨低分子肝素对大鼠移植心脏急性和慢性排斥反应的影响及其机制.方法 以SD大鼠为供者,Wistar大鼠为受者,进行异位(腹部)心脏移植.将受者随机分为急性排斥反应组(简称"急排组")和慢性排斥反应组(简称"慢排组").急排组中,15只于移植当天开始皮下注射低分子肝素200 μg穔g-1穌-1(小剂量者),直至移植心脏停搏;15只皮下注射低分子肝素2000 μg穔g-1穌-1(大剂量者),用药时间同前;以不给低分子肝素者作对照.慢排组所有受者均于移植当天至移植术后第9天腹腔注射环孢素A 5 mg·kg-1·d-1,其中10只还于移植当天至移植后第90天皮下注射低分子肝素2000 μg穔g-1穌-1,10只注射低分子肝素的同时再皮下注射左旋精氨酸甲酯(L-NAME)10mg·kg-1·d-1,以不给低分子肝素和L-NAME者作对照.移植后第5天,处死急排组部分受者,切取移植心脏,根据Stanford标准进行移植物排斥反应的病理学诊断和分级;剩余受者观察移植心脏存活时间.移植后第90天,测定慢排组受者的血NO浓度和移植心脏组织中诱生型NO合酶(iNOS)mRNA表达强度,并行心脏移植物血管病(CAV)评分.结果 急排组中,对照者、小剂量者和大剂量者的排斥反应等级评分分别为(4.20±0.45)分、(3.60±0.55)分和(2.40±0.55)分,移植心脏存活时问分别为(7.30±1.49)d、(8.20±1.47)d和(9.20±1.23)d,大剂量者的排斥反应等级评分明显低于对照者和小剂量者,移植心脏存活时间明显长于对照者和小剂量者(P＜0.05).慢排组中,仅给予低分子肝素者的血NO浓度和iNOS mRNA表达强度明显高于对照者和加用L-NAME者,而其CAV评分明显低于对照者和加用L-NAME者,差异均有统计学意义(P＜0.01).结论 低分子肝素可减轻急、慢性排斥反应程度,延长移植心脏存活时间;其抑制CAV的作用可能是通过上调iNOS mRNA表达水平,进而增加NO的释放来实现的.     

维持大鼠生理需要最短移植肠管长度的探讨

目的探讨维持大鼠生理需要最短移植肠管的长度。方法42只Wistar大鼠随机分为肠切除组(切除组):分别切除大鼠小肠远端的80%(切除Ⅰ组)、70%(切除Ⅱ组)和60%(切除Ⅲ组)及盲肠;同系原位小肠移植组(移植组):切除受体全小肠及盲肠,分别移植小肠近端的20%(移植Ⅰ组)、30%(移植Ⅱ组)和40%(移植Ⅲ组);每组6只。观察大鼠术后体重变化,定期采血检测血清总蛋白(Tp)、白蛋白(Alb)、甘油三酯(Tg)和胆固醇(T-ch)的变化,定期做麦芽糖吸收实验;移植组动物死亡时取移植肠管进行苏木精-伊红染色。结果切除Ⅰ组和移植Ⅰ组大鼠分别于术后(14.8±1.3)d和(9.2±1.6)d死于营养不良。切除Ⅱ组4/6只和切除Ⅲ组全部、移植Ⅱ组2/6只和移植Ⅲ组4/6只大鼠存活超过30d。术后30d时,切除Ⅱ组与移植Ⅱ组、切除Ⅲ组与移植Ⅲ组相比,大鼠的体重增长、血清Tp、Alb、Tg、T-ch之间的差异有非常显著性意义(P<0.001)。结论切除大鼠全小肠及盲肠后,至少需要移植30%的近端小肠才能维持其正常的生理需要。     

地塞米松不同时期给药对小鼠肠缺血再灌注损伤及诱导型一氧化氮合酶活性的影响

目的 评价地塞米松不周时期给药对小鼠肠缺血再灌注损伤及诱导型一氧化氮合酶(iNOS)活性的影响.方法 健康清洁级雄性昆明小鼠35只,体重20～24 g,采用随机数字表法,将其随机分为5组(n=7):假手术组(Ⅰ组)、肠缺血再灌注组(Ⅱ组)、地塞米松缺血前给药组(Ⅲ组)、地塞米松缺血期给药组(Ⅳ组)和地塞米松再灌注即刻给药组(Ⅴ组).采用阻断肠系膜上动脉30 min再灌注的方法制备肠缺血再灌注损伤模型.Ⅰ组只分离肠系膜上动脉,不阻断;Ⅱ组和Ⅲ组分别在缺血前30 min经尾静脉注射生理盐水和地塞米松10 mg/kg;Ⅳ组于缺血5 min时、Ⅴ组于再灌注即刻静脉注射地塞米松10 mg/kg.再灌注3h时处死小鼠,取小肠组织,光镜下观察小肠粘膜病理学结果,采用Chiu评分法对小肠病理损伤进行评分;采用硝酸还原酶法检测一氧化氮(NO)含量,采用比色法检测iNOS的活性.结果 与Ⅰ组比较,Ⅱ组～Ⅴ组肠组织Chiu评分、Ⅱ组、Ⅳ组和Ⅴ组肠组织iNOS活性和NO含量升高(P＜0.05),Ⅲ组肠组织iNOS活性和NO含量差异无统计学意义(P＞0.05);与Ⅱ组比较,Ⅲ组肠组织Chiu评分、iNOS活性和NO含量降低,Ⅴ组肠组织Chiu评分、iNOS活性和NO含量均升高,Ⅳ组上述指标差异无统计学意义(P＞0.05).结论 地塞米松缺血前给药可减轻小鼠肠缺血再灌注损伤,缺血期给药对损伤无明显影响,再灌注即刻给药可加重损伤,可能与地塞米松不同时期用药对iNOS活性影响不同有关.     

L-精氨酸和氨基胍在大鼠肺移植缺血再灌注损伤中的作用

目的 观察L-精氨酸(L-Arg)和氨基胍对大鼠肺移植后缺血再灌注的保护作用.方法 建立大鼠左单肺移植模型,术后随机分为A组(对照组,腹腔注射生理盐水),B组(腹腔注射L-Arg)、C组(腹腔注射氨基胍)和D组(腹腔注射L-Arg和氨基胍),每组6只.移植肺再灌注2 h后,检测肺组织髓过氧化物酶(MPO)、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力、内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)活性并测定移植肺干湿重比(W/D)及静脉血中一氧化氮(NO)含量,观察移植肺的病理学形态.结果 再灌注2 h后,B组移植肺的W/D(5.10±0.21)、MPO(1.74±0.26)U/g和MDA(20.87±2.90)μmol/g均低于A组W/D(5.74 ±0.14)、MPO(2.36±0.32)U/g和MDA(31.33 ±3.46)μmol/g;SOD活性(424.29±27.86)U/mgprot、NO含量(175.12 ±17.40)μmol/L、iNOS活性(3.62 ±0.26)U/mgprot和eNOS活性(5.36±0.28)U/mgprot均较A组SOD活性(268.01±26.06)U/mgpro、NO含量(98.29±6.95)μmol/L、iNOS活性(2.53 ±0.22)U/mgprot和eNOS活性(3.57 ±0.40)U/mgprot高(P＜0.05).C组的NO含量(84.13±5.18)μmol/L、iNOS活性(1.81 ±0.09)U/mgprot均较A组低(P＜0.05).D组的W/D(4.79 ±0.19)、MPO(1.24±0.13)U/g、MDA(14.60±4.14)μmol/g、iNOS活性(1.99±0.17)U/mgprot低于A组,SOD活性(493.75±24.95)、NO含量(149.61±10.70)μmol/L、eNOS活性(5.50±0.27)U/mgprot高于A组(P＜0.05).与B组比较,D组的W/D、MPO、MDA、NO含量、iNOS活性降低,SOD升高(P＜0.05).病理形态学检查显示D组炎细胞浸润及渗出最轻,B组次之,A组和C组最差.结论 移植后再灌注早期应用L-Arg可减轻缺血再灌注损伤,应用氨基胍并不能减轻移植肺的损伤,但联合应用L-Arg和氨基胍优于单纯应用L-Arg.

Abstract：

Objective To investigate the effects of L-arginine (L-Arg) and aminoguanidine on ischemia-reperfusion injury following rat lung transplantation. Methods The models of rats lung transplantation were established and 4 groups ( n = 6 each) were randomly set up: group A ( normal control group)and treated groups B, C and D. In these groups, different medicines (NS, group A; L-Arg, group B;aminoguanidine, group C; L-Arg and aminoguanidine, group D) were intraperitoneally administered to the recipient rats before reperfusion. After reperfusion for 2 h, the lung graft was harvested for measurements of lung wet/dry ratio ( W/D ) , myeloperoxidase ( MPO ) , malondialdehyde ( MDA ) , superoxide dismutase (SOD) , endothelial nitric oxide synthase (eNOS) , inducible nitric oxide synthase (iNOS). The contents of plasma nitric oxide (NO) were determined. The pathological changes in the lung grafts were observed.Results After reperfusion for 2 h, W/D (5. 10 ±0.21), MPO (1.74 ±0.26) U/g, MDA (20.87 ±2. 90) μmol/g in group B were significantly lower [W/D (5. 74 ± 0. 14), MPO (2. 36 ± 0. 32) U/g,MDA (31. 33 ±3.46) μmol/g] (P ＜ 0. 05), and the levels of SOD (424. 29 ± 27. 86) U/mg protein,NO (175. 12 ± 17. 40) μmol/L, iNOS (3. 62 ±0. 26) U/mg protein and eNOS (5. 36 ±0. 28) U/mg protein were significantly higher than in group A [SOD (268.01 ±26.06) U/mg protein, NO (98.29 ±6.95) μmol/L, iNOS (2.53 ±0.22) U/mg protein and eNOS (3. 57 ±0.40) U/mg protein] (P＜0. 05). The contents of NO (84. 13 ±5. 18) μmol/L and iNOS (1. 81 ±0. 09) U/mg protein in group C were significantly lower than in group A (P ＜ 0. 05). W/D (4. 79 ± 0. 19) , MPO (1. 24 ± 0. 13 ) U/g,MDA (14. 60 ±4. 14) μmol/g, iNOS (1. 99 ±0. 17) U/mg protein were significantly lower than in group A (P ＜0. 05) , and SOD (493. 75 ±24. 95) , NO (149. 61 ± 10. 70) μmol/L and eNOS (5. 50 ±0. 27)U/mg protein in group D were significantly higher than in group A (P＜0. 05). W/D, MPO, MDA, NO and iNOS in group D were significantly reduced as compared with group B (P ＜ 0. 05 ) , and SOD was significantly increased in group B ( P ＜ 0. 05 ) . The pathological examination revealed that the inflammatory cell infiltration in group D was the mildest, followed by groups B, A and C. Conclusion The L-Arg could alleviate the lung ischemia-reperfusion injury after transplantation, the combined used of L-Arg and aminoguanidine could obtain better effects than L-Arg used alone. The aminoguanidine used alone could not alleviate ischemia-reperfusion injury after transplantation.     

诱导型一氧化氮合成酶对同系大鼠移植肠运动功能的作用

目的 观察诱导型一氧化氮合成酶(iNOS)对同系原位全小肠移植术后早期移植肠运动功能的影响.方法 分为对照组、移植组、L-NIL治疗组,每组12只大鼠.对照组行十二指肠造瘘术,另两组均行同系原位全小肠移植及十二指肠造瘘术,术后分别给予生理盐水、L-N6-(1-亚氨乙基)-赖氨酸(L-NIL).于术后2 d,各组取6只获取肠段行病理组织学检查,观察炎性损伤程度,并采用RT-PCR和免疫组织化学方法检测iNOS mRNA及蛋白表达水平.各组另6只行小肠传输实验,观测小肠传输功能.结果 移植组呈明显炎性损伤改变,iNOS mRNA及蛋白表达水平(1.278±0.142)%,(56.33±5.16)%较对照组(0.066±0.016)%,(9.17±3.17%)上调(P＜0.01),较对照组小肠传输延迟(P＜0.01).L-NIL治疗组炎性损伤程度较移植组减轻,iNOS mRNA及蛋白表达水平(0.588±0.096)%,(26.17±4.14)%较移植组下调(P＜0.01),且小肠传输延迟有改善(P＜0.01).结论 iNOS在术后早期移植肠炎症损伤及其引发的肠运动功能障碍中可能起重要作用.     

输注鼠基因工程Treg细胞抑制小鼠异基因骨髓移植后移植物抗宿主病

目的 探讨输注慢病毒载体介导的鼠基因工程调节性T淋巴细胞(Treg细胞)对小鼠异基因骨髓移植后移植物抗宿主病(GVHD)的影响.方法 利用慢病毒载体介导,将鼠又状头螺旋转录因子(Foxp3)基因转导入Balb/c小鼠的CD4~+ CD25~-T淋巴细胞,即为基因工程Treg细胞.以Balb/c小鼠为供者,C57BL/6小鼠为受者,进行异基因骨髓移植,实验分4组进行:(1)工程Treg组经受鼠尾静脉输注供鼠骨髓细胞5×10~6个+脾细胞5×10~6个+基因工程Treg细胞5×10~6个;(2)移植对照组经受鼠尾静脉输注供鼠骨髓细胞5×10~6个+脾细胞5x10~6;(3)单纯照射组经受鼠尾静脉输注RPMI 1640培养液0.2ml;(4)空载体对照组经受鼠尾静脉输注供鼠骨髓细胞5×10~6个+脾细胞5×10~6个十空载体转导的CD4~+ CD25~-T 淋巴细胞5×10~6个.每天观察受鼠存活情况;记录GVHD的发生情况;各组均于小鼠濒死前取其肝脏、小肠、皮肤等组织,进行病理学观察;取长期存活(超过60d)的受鼠骨髓细胞,检测嵌合情况.结果 单纯照射组、移植对照组、工程Treg组和空载体对照组小鼠存活时间分别为(8.8±0.6)d、(36.7±2.5)d、(51.6±4.0)d和(34.1±2.3)d,工程Treg组小鼠存活时间明显长于其他各组,差异有统计学意义(P<0.05).移植对照组及空载体对照组小鼠肝脏、皮肤和小肠病理切片均存在GVHD病理改变,工程Treg组长期存活小鼠的肝脏、皮肤和小肠常规病理切片结构基本正常,未见GVHD病理表现,该组GVHD评分明显低于移植对照组及空载体对照组.结论 小鼠异基因骨髓移植时联合输注基因工程Treg细胞可有效减少GVHD的发生,减轻其严重程度.     

输注供鼠骨髓间充质干细胞延长肾移植大鼠的存活时间

目的 探讨在同种大鼠肾移植中输注供者骨髓间充质干细胞(MSC)对急性排斥反应的影响以及延长受鼠存活时间的作用.方法 取Wistar大鼠骨髓,分离和培养其MSC.以Wistar 大鼠为供者,Lewis大鼠为受者,建立同种大鼠肾移植模型.根据受鼠处理方式的不同,分为低剂量MSC组、高剂量MSC组、CsA组及对照组,低剂量MSC组和高剂量MSC组于移植前后分别多次输注1×106个和t×107个供者MSC,CsA组于术后2d开始腹腔内注入CsA 0.5 mg·kg-1 ·d-1,以腹腔内注射PBS作为对照.移植后,比较各组受鼠的存活时间,观察各组移植肾功能及移植肾组织病理学改变.结果 低剂量MSC组、高剂量MSC组、CsA组及对照组受鼠的存活时间分别为(21.7±7.2)d、(31.2±14.3)d、(34.9±15.7)d及(9.0±2.3)d;低剂量MSC组、高剂量MSC组和CsA组存活时间均明显长于对照组(P＜0.01),而低剂量MSC组存活时间明显短于高剂量MSC组和CsA组(P＜0.05).术后第4天,高剂量MSC组和CsA组移植肾组织形态和结构基本正常;对照组移植肾组织则表现出典型的急性排斥反应,出现广泛间质性浸润,肾小管炎症和片状坏死、出血,肾小球炎症浸润严重;而与对照组相比,低剂量MSC组急性排斥反应的病理表现则要明显减轻.结论 同种肾移植大鼠输注供者MSC后,可以达到有效的免疫调节作用,并且可明显延长大鼠的存活时间,呈MSC剂量依赖性.     

应用电子顺磁共振技术研究大鼠肾移植缺血再灌注过程中的NO水平及变化

目的应用电子顺磁共振(EPR)技术动态监测大鼠移植肾缺血再灌注过程中一氧化氮(NO)的产生及其作用. 方法雄性LEW大鼠75只,8～10周龄,体重200～230 g.30只作为供体,供肾0 ℃保存24 h.其余45只分3组,每组15只.第1组为对照组,麻醉后开腹,暴露30 min后关腹;第2组为单纯肾移植组,行同基因肾移植,移植肾再灌注同时切除双肾;第3组为肾移植加N-硝基-L-精氨酸甲脂(L-NAME)组,移植肾再灌注同时切除双肾,供体和受体术前2 h分别给予L-NAME 30 mg/kg.应用EPR动态测定移植肾恢复血流前及之后各时间点NO水平.测定恢复血流后24 h和120 h血肌酐、肾小球滤过率及肾组织羰基含量. 结果单纯肾移植组再灌注后15 min NO开始显著增加并持续上升,120 min达较高水平后迅速下降,到210 min恢复再灌注前水平;肾移植加L-NAME组呈类似变化趋势,但NO水平明显低于前组.L-NAME组的24 h和120 h血肌酐水平均显著高于单纯移植组(P<0.05);24 h(P<0.05)和120 h(P<0.01)肾小球滤过率均显著低于移植组.L-NAME组的24h组织羰基含量显著低于单纯移植组(P<0.05),120 h高于单纯移植组(P<0.05). 结论冷缺血移植肾再灌注过程中,NO早期增加并迅速下降,对移植肾以保护为主.应用L-NAME抑制NO后不利于移植肾功能恢复.     

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.     

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.