不同品系大鼠之间肝移植排斥反应的比较研究

目的比较不同品系大鼠之间肝移植排斥反应特点。方法依据大鼠不同品系分成对照组SD→SD(A组),实验组Wistar→SD(B组)、Lewis→BN(C组)以及DA→Lewis(D组)4个组,采用Kamada双袖套法建立大鼠原位肝移植模型。比较各组受体大鼠术后10 d血清肝功能指标[丙氨酸转氨酶(ALT)、总胆红素(TB)和白蛋白(Alb)]、血清白细胞介素(IL)-2和IL-10水平、急性排斥反应组织病理学分级和术后平均生存时间。结果与A、B组比较,C组和D组的血清ALT和TB明显升高,Alb明显降低,差异均有统计学意义(均为P0.05)。与C组比较,D组的TB明显升高,Alb明显降低,差异均有统计学意义(均为P0.05)。与A组比较,B、C、D组大鼠血清IL-2和IL-10水平均明显升高,C组和D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P0.05)。与B组比较,C组和D组大鼠血清IL-2水平明显升高,D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P0.05)。与C组比较,D组大鼠血清IL-2水平明显升高,D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P0.05)。肝组织病理学检查显示,A组大鼠肝组织未见明显排斥反应,排斥活动性指数(RAI)评分(1.8±0.7)分;B组RAI评分(3.1±1.3)分,属轻度或不明确性排斥反应;C组RAI评分(6.9±0.8)分,属中~重度排斥反应;D组RAI评分(8.8±0.5)分,属重度排斥反应。各组间RAI评分比较以及组间两两比较,差异均有统计学意义(均为P0.05)。A组、B组、C组、D组受体大鼠术后平均生存时间分别为(119.3±1.9)d、(116.9±8.3)d、(53.4±6.1)d、(12.1±2.4)d,A组与B组的生存时间比较差异无统计学意义,余各组两两比较差异均有统计学意义(均为P0.05)。结论 4种组合中,大鼠DA→Lewis模型排斥反应最剧烈,Lewis→BN次之,而Wistar→SD最轻,接近于免疫耐受。     

雷公藤多甙对大鼠原位肝移植急性排斥反应的影响

目的 探讨雷公藤多甙(TⅡ)对大鼠肝移植术后急性排斥反应的抑制作用和机制。方法 用“二袖套法”建立Wistar→SD大鼠原位肝移植模型，分对照组(n＝12)和TⅡ治疗组(n＝13)，移植术后第7d两组各杀死部分大鼠，测肝功能、肝组织病理和脾淋巴细胞IL—2活性，其余大鼠留作观察存活时间。结果术后第7d，TⅡ组肝功能损害和移植肝病理急性排斥反应程度轻于对照组，IL—2活性低于对照组。TⅡ组大鼠术后存活时间比对照组明显延长。结论 TⅡ可明显延长肝移植术后存活时间，减轻急性排斥反应程度。     

CTLA4-Ig基因修饰骨髓间充质干细胞抑制大鼠肝移植排斥反应

目的探讨细胞毒性T淋巴细胞相关抗原4免疫球蛋白(CTLA4-Ig)基因转染骨髓间充质干细胞(MSC)在抑制大鼠原位肝移植排斥反应的作用及机制。方法采用重组腺病毒(Ad)5-CTLA4-Ig转染MSC。转染72 h后,提取细胞总蛋白,采用蛋白质印迹法检测转染后MSC中CTLA4-Ig的蛋白表达。采用细胞计数试剂盒(CCK)-8方法检测未转染和转染后的MSC对外周血淋巴细胞增殖的抑制作用。以雄性Lewis大鼠为供体(40只);以雄性Brown Norway(BN)大鼠为受体(40只)。采用改良的Kamada两袖套法进行原位肝移植,建立大鼠原位肝移植急性排斥反应模型。40只受体大鼠随机分为4组,每组10只。其中对照组(A组),于肝移植时门静脉输注生理盐水;MSC治疗组(B组),于肝移植时门静脉输注MSC;转基因MSC治疗组(C组),于肝移植时门静脉输注转基因MSC;免疫抑制剂治疗组(D组),于肝移植时门静脉输注生理盐水,术后即给予环孢素(CsA)1.5 mg/(kg·d)肌内注射,连续8 d。每组大鼠取5只观察生存情况。每组其余5只于术后第9日处死,检测外周血细胞因子白细胞介素(IL)-2、IL-4、干扰素(IFN)-γ水平,光学显微镜下观察肝组织病理学变化和排斥反应程度。结果重组Ad5-CTLA4-Ig转染MSC 72 h后,蛋白质印迹法可检测到转染后的MSC中有CTLA4-Ig的蛋白表达。当未转染的MSC∶外周血单核细胞比例为1∶10、1∶20时,MSC抑制淋巴细胞增殖的作用分别为85.60%、76.69%。重组Ad5-CTLA4-Ig转染MSC 72 h后,在相同的数量比下,其抑制淋巴细胞增殖的作用分别为90.50%、84.20%;与未转染的MSC比较,转染后抑制淋巴细胞增殖的作用增强(P0.05)。A、B、C、D组大鼠肝移植术后存活时间分别为(13±3),(41±6),(90±15),(102±18)d。A、B、C组的大鼠术后存活时间比较差异有统计学意义(P0.05),C组和D组的大鼠术后存活时间比较差异无统计学意义(P0.05)。与A组比较,B组和C组的IL-4水平明显升高;与B组比较,C组的IL-4水平明显升高,差异均有统计学意义(均为P0.05);C组和D组的IL-4水平比较,差异无统计学意义(P0.05)。与A组比较,B组和C组的IL-2、IFN-γ水平明显降低,C组的IL-2、IFN-γ水平亦低于B组,差异均有统计学意义(均为P0.05),C组和D组的IL-2、IFN-γ水平比较,差异无统计学意义(P0.05)。大鼠肝组织病理检查结果显示,A组移植肝发生重度排斥反应,B组移植肝亦发生排斥反应,但与A组比较程度较轻。C组与D组移植肝有轻度排斥反应。结论重组Ad-CTLA4-Ig转染MSC可抑制肝移植排斥反应,其效果优于MSC单独应用。     

大鼠肝移植排斥反应时γ干扰素及白细胞介素10的表达及意义

目的 探讨大鼠肝移植排斥反应时γ干扰素(IFN-γ)及白细胞介素10(IL-10)的表达及意义.方法 采用改良的Kamada"二袖套法"制备大鼠原位肝移植模型,同系移植组供、受者均为SD大鼠;同种异体移植组的供者为Wistar大鼠,受者为SD大鼠;另设假手术组.术后7 d处死动物,观察移植肝脏的组织学变化,检测血清IFN-γ和IL-10的含量,以及移植肝脏内IFN-γ和IL-10 mRNA的表达.结果 同种异体移植组移植肝脏有较多坏死肝细胞,汇管区及中央静脉周围可见以淋巴细胞为主的炎症细胞浸润,胆管上皮细胞可见胞浆空泡变性、核固缩或碎裂,整个肝小叶结构紊乱.同系移植组肝脏组织结构仅有轻度缺血再灌注损伤表现,汇管区有较少炎症细胞浸润,胆管上皮细胞结构和肝小叶结构基本正常.同种异体移植组血清IFN-γ为(386.7±14.4)Pg/ml,明显高于同系移植组的(159.8±16.5)pg/ml(P<0.05);同种异体移植组血清IL-10为(126.3±13.1)pg/ml,明显低于同系移植组的(288.3±17.1)pg/ml(P<0.05).同种异体移植组移植肝组织内IF-γ mRNA表达水平明显高于同系移植组(P<0.05),而IL-10 rnRNA表达水平明显低于同系移植组(P<0.05).结论 大鼠肝移植排斥反应时IFN-γ表达明显升高,IL-10表达明显降低;T_H1/T_H2型细胞因子的动态平衡可能在大鼠肝移植排斥反应中起着重要作用.     

Lewis型至Brown Norway型大鼠肝移植急性排斥反应模型的建立

目的:建立Lewis(LEN)型到Brown Norway(BN)型大鼠肝移植急性排斥反应模型并观察其排斥反应特点.方法:采用近交系雄性LEW大鼠为供体,BN大鼠为受体,改良"二袖套"法建立模型36例,术后第3、7和10天分别随机解剖8只受体大鼠,检测血清肝功能生化指标,观察肝脏病理组织学变化,剩余受体大鼠观察生存时间.结果:受体大鼠术后第3、7和10天的血清总胆红素分别为(8.75±1.98)μmol/L、(21.12±2.03)μmol/L和(53.63±4.24)μmol/L,丙氨酸转氨酶(ALT)分别为(291.88±6.83)U/L、(462.33±16.98)U/L和(906.25±68.55)U/L,两者术后均逐渐升高;受体大鼠术后第3天光镜下汇管区见混合性炎细胞浸润和静脉内皮炎,伴部分肝实质变性,排斥活动指数(RAI)为4～5;术后第7天排斥反应加重,并出现小胆管增生,RAI为5～7;术后第10天排斥反应最严重,出现明显汇管区结构破坏,肝小叶消失,大量淋巴细胞和单核细胞浸润,静脉内皮炎明显,肝实质桥接坏死,RAI为7～9分;受体大鼠的临床表现及生存情况与病理变化一致.结论:LEW到BN大鼠组合有助于建立稳定可靠的肝移植急性排斥模型,且该模型的排斥反应特点与临床相似.     

CD4+CD25+T细胞联合CD154单抗抑制大鼠肝移植急性排斥反应的研究

目的探讨CD4 CD25 T细胞联合应用CD154单抗在抑制大鼠肝移植急性排斥反应中的作用。方法分离Lewis大鼠脾脏CD4 _CD25 T细胞后与DA大鼠脾细胞单向混合淋巴细胞反应行体外激活。用"二袖套法"行DA到Lewis的原位肝移植48例。A组为对照组;B、C组单独术前回输体外激活的CD4 CD25 T细胞或术后腹腔注射抗CD154单抗;D组联合应用CD4 CD25 T细胞和CD154单抗。每组大鼠12对。术后7 d各组处死6只受体,检测移植肝内T细胞亚群和细胞因子水平。余大鼠观察生存情况,死亡大鼠观察移植肝病理变化。结果D组受体生存期(52.00±10.64)d明显长于B、C组(P<0.01);移植肝内CD4 CD25 T细胞比例(16.43±4.28)%明显高于B、C组(P<0.05、P<0.01),而淋巴细胞浸润数量[(3.47±1.21)%×106]和(CD8 T细胞百分比(14.19±3.02)%明显低于B、C组(P<0.05、P<0.01);移植肝内白细胞介素- 2(IL-2)水平(6.44±1.83)ng/L低于B、C组(P<0.05),IL-10(43.72±7.55)ng/L和转化生长因子-β1(TGF-β1)(270.06±46.91)ng/L明显高于B、C组(P<0.05、P<0.01)。结论联合应用CD154单抗能明显增强CD4 CD25 调节性T细胞对大鼠肝移植急性排斥反应的抑制作用。     

抗CD-40L单抗加小剂量、短程CsA对肝移植大鼠生存期和Th1/Th2平衡偏移的影响

目的 采用抗CD-40L单抗加小剂量CsA的联合免疫治疗,观察其对大鼠肝移植受体生存时间和Th1/Th2细胞因子谱变化的影响.方法 在建立稳定大鼠肝移植模型的基础上,将整个实验分为4组.A组(同基因对照组):SD→SD;B组(同种异体基因免疫排斥组):SD→Wistar,不用任何治疗措施;C组:SD→Wistar,CsA应用d1～d5;D组:SD→Wistar,CsA应用d1～d5加抗CD-40L(CD-154)单抗应用d0、d2.观察各组大鼠肝移植受体生存时间,移植后第7天用ELISA法检测外周血细胞因子水平.结果 A组、D组受体大鼠均可长期存活,B组生存时间仅为(13.8±2.4)d.IL-2、IFN-γ在B组的血清水平显著高于其余各组(P＜0.05),TNF-α在B组的表达水平高于不同免疫抑制组,但差异无显著统计学意义.IL-4、IL10较A组均有所增加,尤其D组的IL-10表达水平较B组显著增高(P＜0.05).结论 抗CD-40L单抗加小剂量CsA(伴或不伴DSBT)联合免疫治疗,可有效延长大鼠肝移植受体的生存时间,Th2类细胞因子的高水平表达与诱导移植耐受、抑制排斥反应有重要关联,有助于大鼠肝移植受体和移植肝的长期存活.     

骨化三醇预防大鼠原位肝移植后急性排斥的动态观察

目的探讨骨化三醇在预防大鼠原位肝移植后急性排斥反应中的作用。方法大鼠原位肝移植分为Wistar→Wistar同基因组 (Ⅰ组 ) ,SD→Wistar急性排斥组 (Ⅱ组 )和SD→Wistar环孢菌素治疗组 (Ⅲ组 ) ,SD→Wistar骨化三醇治疗组 (Ⅳ组 ) ,在移植后 1,5 ,7,15 ,30d各个时点检测肝脏功能、急性排斥反应、细胞因子表达等指标。结果Ⅳ组大鼠移植后 4 /6生存期大于 10 0d ,与Ⅱ组比较差异有显著意义 (P <0 0 0 1)。Ⅳ组大鼠移植后各时点平均AST(12 7± 4 1)U/L～ (36 0± 10 4 )U/L ,平均BIL(13± 5 )mmol/L～ (38± 11)mmol/L(与Ⅱ组比较 ,P <0 0 5 )。Ⅳ组移植后各时点平均排斥反应活动度积分 0分～ (3 3± 1 6 )分 (与Ⅱ组比较 ,P <0 0 5 )。Ⅳ组大鼠移植后各时点肝组织内IFN γmRNA表达明显减弱 ,IL 10mRNA表达明显增强 (与Ⅱ组比较 ,P <0 0 5 )。结论原位肝移植后骨化三醇治疗可以诱导细胞因子分泌向TH2型偏移 ,有效抑制急性排斥反应。     

输注受者骨髓间充质干细胞对肝移植大鼠免疫功能的影响

目的 观察肝移植同时输注受者骨髓间充质干细胞(MSCs)对受者肝移植免疫功能的影响.方法 实验分为4组:A组SD大鼠只行剖腹探查;B、C、D组各组行Wistar-SD大鼠肝移植同时,C组提取受者MSCs同期经门静脉输注给受者,D组给予肌注CsA,B组给予门静脉输注生理盐水.观察术后第1、7、14天肝功能的变化、病理改变和细胞因子变化.结果 肝移植同时输注受者MSCs,谷氨酸转移酶、血清总胆红素较对照组显著降低,病理改变仅呈急性轻度排除反应,与肌注CsA组相似,而单纯移植组呈急性重度排除反应.术后第7天,白细胞介素(IL)-2和干扰素(IFN)-γ浓度,C组分别为(443.89±2.39)、(347.55±3.35)ng/L,B组分别为(600.36±2.98)、(373.77±1.81)ng/L,而IL-4和IL-10浓度,C组分别为(126.99±1.18)、(147.40±1.07)ng/L,B组分别为(102.02±0.94)、(111.03±1.15)ng/L,C组和B组比较,差异有统计学意义(P＜0.05).结论 肝移植同时输注MSCs,可通过抑制Th1细胞因子的表达,减轻受者对移植肝的排斥反应.     

未成熟树突状细胞诱导协调性异种胰岛移植耐受的研究

目的　研究未成熟树突状细胞 (DC)在协调性异种胰岛移植中的免疫耐受诱导作用。方法　分别应用 2 0 μg/L粒细胞集落刺激因子 (GM CSF)和 5 0 0 μg/LGM CSF 2 0 0 μg/L白细胞介素4 (IL 4) ,从BALB/c受鼠骨髓培养未成熟DC及成熟DC ,然后负载Wistar大鼠的主要组织相容性复合物 (MHC)抗原。将两种DC回输至糖尿病小鼠体内 ,7d后分别将Wistar大鼠和SD大鼠胰岛移植于糖尿病小鼠左肾包膜下 ,监测移植物存活情况 ,检测T细胞增殖反应 ,并进行病理切片检查。结果　负载MHC抗原成熟DC预处理的BALB/c小鼠体内胰岛迅速被排斥 ,负载MHC抗原未成熟DC预处理的BALB/c小鼠胰岛存活时间明显延长 (P <0 .0 1 ) ,但以SD大鼠作为供者的胰岛移植物迅速被排斥。耐受鼠的脾细胞对Wistar大鼠脾细胞的增殖反应微弱 ,而排斥鼠脾细胞则出现明显增殖反应。结论　未成熟DC预处理受者可诱导T细胞无能 ,并有效延长异种胰岛移植后的存活时间。     

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 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.     

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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

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.     

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.     

Intrathecal administration of sameridine to patients subjected to arthroscopic knee joint surgery

Background: Sameridine, a new substance with both local anesthetic and opioid effects, was administered intrathecally for the first time to humans, i. e. in patients subjected to arthroscopic knee joint surgery.
Method: A dose-escalating (10, 15, 20 and 25 mg), open study was performed in 33 patients. Only two patients were included in the 25 mg group.
Results: Sameridine provided good quality of surgical anesthesia in all patients except those receiving 10 mg. The maximum level of sensory block, Th5–Th7, was reached within 30 min with a median duration of 3.6–3.9 h. The motor block was more profound with increasing dose, but never lasted longer than the sensory block. The influence on heart rate and blood pressure was minor and atropine and ephedrine were needed in four patients. No clinically significant ECG-changes were detected and no arrhythmias were recorded. Oxygen saturation and respiratory rate did not decrease in a clinically significant way and were not affected by concomitant morphine given i. v. postoperatively. There were few side-effects, the most frequent being mild pruritus (10/33).
Conclusion: Sameridine provided clinically adequate anesthesia for the patients receiving the doses of 15, 20 and 25 mg. Further studies are needed to evaluate the substance and it is of great interest to clinically investigate the opioid component with respect to postoperative analgesia.     

Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.