环氧合酶-2在大鼠肝移植缺血再灌注损伤中对IP／TP的影响

目的 探讨前列腺素I2受体(IP)、血栓素A2受体(TP)与环氧合酶-2(COX-2)在肝移植缺血再灌注损伤中的相互作用及其机理.方法 雄性SD大鼠随机分为3组:正常对照组(n=16)、原位肝移植组(n=32)和尼美舒利(nimesulide)干预组(n=32),分别于手术后3、6、12 和24 h取血液和肝组织标本备检.RT-PCR检测肝组织中IP、TP及COX-2 mRNA表达; 免疫组化法检测COX-2在肝组织中的定位及表达; HE染色确定组织损伤程度; 检测血清ALT和AST变化.结果 免疫组化染色结果显示,原位肝移植组COX-2蛋白表达比正常对照组明显增强,主要分布于汇管区肝窦内皮细胞、肝细胞及巨噬细胞内,尼美舒利干预组COX-2蛋白表达较原位肝移植组明显减弱. 原位肝移植组中IP mRNA、TP mRN及COX-2 mRNA表达水平均比正常对照组明显升高,IP/TP比值也明显升高(P＜0.05). 尼美舒利干预组IP mRNA和TP mRNA表达水平(术后6及12 h)比原位肝移植组明显降低(P＜0.05),IP/TP比值手术后3、6及24 h较原位肝移植组降低(P＜0.05); COX-2 mRNA表达水平在术后6、12及24 h低于原位肝移植组(P＜0.05).HE染色见原位肝移植组肝损伤明显,尼美舒利干预组肝损害较原位肝移植组明显减轻; 血清中各时点AST和3、6及12 h的ALT在原位肝移植组明显增高于其他2组(P＜0.05),且均在再灌注后6 h达峰值.结论 IP/TP的平衡在肝移植缺血再灌注损伤中具有重要作用,抑制COX-2的表达可通过改善IP/TP的失衡从而减轻肝移植缺血再灌注损伤.     

小鼠半肝移植后早期T细胞激活基因-3的变化

目的 研究不同冷缺血损伤条件下,小鼠半肝移植后早期肝内趋化因子T细胞激活基因-3(T cell activation gene-3,TCA-3)的变化. 方法 建立C57BL/6小鼠全肝和部分肝脏移植模型,分为全肝对照组和半肝移植实验组.冷保存时间分为冷缺血1、4和8h.术后4、24 h收集标本,核糖核酸酶保护试验评估各组移植术后TCA-3的mRNA表达水平.组织病理学观察肝脏移植物的缺血再灌注损伤情况.结果 共行小鼠半肝移植45只,全肝移植30只.2组小鼠术后7d的存活率均为100％.定量分析证实:全肝移植术后4h,冷缺血1、4、8h组TCA-3的表达保持在较低水平,但半肝移植组TCA-3的表达明显升高(F=7.41,P＜0.05).术后24 h,全肝移植组和半肝移植组TCA-3的表达均明显降低,2组比较差异无统计学意义(P＞0.05).组织学检查发现半肝移植物表现为更严重的冷缺血损伤. 结论 TCA-3在半肝移植术后早期明显升高,在冷缺血损伤机制中起重要作用,TCA-3可能是减轻半肝移植物冷缺血损伤的早期治疗靶点.     

添加谷氨酰氨强化的早期肠内营养对肝移植大鼠肠屏障的保护作用

目的 观察使用添加谷氨酰胺(Gln)强化的早期肠内营养(EEN)对原位肝移植大鼠肠黏膜屏障的影响.方法 取Wistar大鼠,采用随机数字表法将大鼠分为对照组、肝移植组和EEN组.对照组仅手术分离肝十二指肠韧带;肝移植组和EEN组按两袖套法进行肝移植,供者为同批Wistar大鼠.术前3、2、1d及术后3h开始,给予EEN组受鼠添加了Gln(0.3 g·kg-1 ·d-1)的肠内营养混悬液(125 ml·kg-1 ·d-1)灌胃,肝移植组受鼠给予等体积生理盐水灌胃;对照组无特别处理.术后检测各组小鼠血浆内毒素、D-乳酸及血清肿瘤坏死因子α (TNF-α)的含量,测定肠黏膜TNF-αmRNA的表达,并对回肠肠壁组织进行超微结构观察.观察和记录各组小鼠的存活时间.结果 肝移植组和EEN组术后12、24和72 h的血浆内毒素、D-乳酸及血清TNF-α含量均明显高于对照组(P＜0.01),而EEN组术后24和72 h时较上述指标肝移植组均明显下降(P＜0.01).电镜下,对照组回肠黏膜上皮间隙正常,微绒毛排列整齐;术后12、24和72 h时,肝移植组小肠黏膜上皮间隙扩大,上皮细胞线粒体肿胀,微绒毛肿胀、空泡化,而EEN组超微结构的改变较肝移植组明显减轻.肝移植组和EEN组术后TNF-α mRNA表达明显升高(P＜0.01),而EEN组较同时点肝移植组的TNF-αmRNA表达明显下降(P＜0.01).对照组存活时间明显长于肝移植组和EEN组(P＜0.05),而EEN组存活时间较肝移植组明显延长(P＜0.05).结论 肝移植后可导致肠黏膜屏障损害,添加Gln强化的EEN对肝移植大鼠肠黏膜屏障具有明显的保护作用,可明显延长肝移植后大鼠的存活时间.     

灯盏花素预处理供肝减轻大鼠肝移植后早期缺血再灌注损伤

目的 研究应用灯盏花素对供肝进行预处理,减轻大鼠肝移植术后早期缺血再灌注损伤的作用.方法 以SD大鼠作为肝移植供、受者,采用随机数字表法将受鼠分为4组.A组和C组供肝未经灯盏花素预处理,B组和D组供肝经含20 mg/L灯盏花素的UW液预处理;A组和B组供肝冷缺血时间为30～40 min,C组和D组为12 h.术后检测各组受鼠的凝血功能、肝功能、血清血栓调节蛋白(TM)含量、凋亡蛋白酶-3 (Caspase-3)活性及核因子-kB(NF-kB)相对表达量,观察各组移植肝组织病理学变化和肝细胞凋亡情况.结果 术后3d,C组与D组受鼠死亡率分别为40.0％(8/20)和29.4％(5/17),差异无统计学意义(P＞0.05);术后4组间凝血功能无明显变化(P＞0.05).与C组比较,术后早期D组肝功能、肝组织病理学改变及肝细胞凋亡均明显改善(P＜0.01),血清TM含量、Caspase-3活性及NF-kB表达量均明显降低(P＜0.01).术后A组和B组的缺血再灌注损伤明显较轻,两组间上述指标的差异均无统计学意义(P＞0.05).结论 应用灯盏花素对供肝进行预处理,能够减轻大鼠肝移植术后由冷保存时间较长引起的缺血再灌注损伤,其机制可能与抑制凋亡相关的信号通路和减轻肝脏微循环内皮细胞损伤有关.     

联合应用厄贝沙坦和依达拉奉对大鼠小体积移植肝的保护作用

目的 探讨联合使用厄贝沙坦和依达拉奉在大鼠小体积供肝移植早期中对移植肝的保护作用及机制.方法 取体重相差20～30g的150对SD大鼠作为肝移植供、受者,其中小体重大鼠作为供者.按随机数字表法将大鼠分为移植对照组(A组)、依达拉奉实验组(B组)、厄贝沙坦实验组(C组)、厄贝沙坦联合依达拉奉实验组(D组)及假手术对照组(E组).采用大鼠30％部分肝移植模型,按二袖套法进行大鼠原位肝移植.术后观察各组受鼠的存活情况,监测门静脉压和肝功能变化,术后6和24 h,检测移植肝组织内SOD活性及MDA含量,采用逆转录实时聚合酶链反应检测移植肝组织Egr-1 mRNA、ET-1 mRNA及Bax mRNA的表达,采用原位末端转移酶标记法检测移植肝细胞的凋亡情况.结果 术后7d,A、B、C、D及E组累积存活率分别为8.33 (1/12),33.3％(4/12),58.7％ (7/12),83.3％ (10/12)和100％(12/12),各组间差异均有统计学意义(P＜0.01).与对照组比较,各实验组门静脉压的变化,术后6和24 h的ALT和AST水平,MDA含量和SOD活性,Egr-1 mRNA、ET-1 mRNA及Bax mRNA的相对表达量,以及肝细胞凋亡指数等指标的检测结果均较优,尤以D组最为显著,各组间上述指标的两两比较,差异均有统计学意义(P＜0.05或P＜0.01).结论 联合使用厄贝沙坦和依达拉奉可通过降低门静脉压和抗氧化作用(减轻移植肝缺血再灌注损伤)的双重保护作用减轻大鼠小体积肝移植术后早期移植肝的损伤,且联合用药效果好于单用其中一种药物.     

血红素氧化酶-1在大鼠肝移植中保护作用的研究

目的 探讨改变血红素氧化酶-1(HO-1)的活性对大鼠同种异体原位肝移植的影响.方法 用二袖套法建立大鼠同种异体原位肝移植模型,实验分为4组:实验对照组(n=44):供体鼠术前24 h腹腔注射生理盐水5 ml/kg;氯化血红素组(n=44):供体鼠术前24 h腹腔注射氯化血红素100 mg/kg,在供肝4℃生理盐水保存期间,经门静脉注入氯化血红素100 mg/kg;锌原卟啉组(n=44):供体鼠术前24 h腹腔注射锌原卟啉5 mg/kg,在供肝4℃生理盐水保存期间,经门静脉注入锌原卟啉5 mg/kg;正常大鼠作为正常对照组(n=5).分别应用RT-PCR及免疫组化技术检测移植肝脏中HO-1 mRNA及蛋白表达,并用流式细胞仪分析移植肝脏肝细胞的凋亡率.结果 肝移植术后供体肝HO-1表达增强.肝移植术后氯化血红素组HO-I mRNA表达水平高于实验对照组,血清ALT和AST水平低于实验对照组(P<0.05);锌原卟啉组术后肝组织HO-1 mRNA表达水平低于实验对照组(P<0.05),血清ALT和AST水平高于实验对照组(P<0.05).肝移植术后48 h肝细胞凋亡率锌原卟啉组最高,氯化血红素组最低,实验对照组介于二者之间,组间差异有统计学意义(P<0.05).术后7 d实验对照组、氯化血红素组及锌原卟啉组3组的生存大鼠分别为7/12、9/12和4/12,组间差异均有统计学意义(P<0.05).结论 肝移植手术过程可促进大鼠肝脏H()-1表达增强;术前采用药物诱导HO-1可降低移植术后肝细胞凋亡率,减轻肝脏损伤程度,提高术后生存率.     

血管内皮生长因子改善大鼠肝移植术后肝功能

目的 探讨血管内皮生长因子(vascular endothelial growth factor, VEGF)对大鼠部分肝移植术后肝功能的影响.方法 建立大鼠30%肝移植模型.分实验组、对照组,每组60只,分别于术后注射鼠重组VEGF、生理盐水.在术后0、12、24、72、168h监测血清ALT、AST、透明质酸(hyaluronic acid, HA)变化.光镜下观察肝窦结构破坏及炎性细胞浸润程度.结果 在72h,实验组血清ALT、AST、HA较对照组明显降低(t=4.681,4.252,2.853,P<0.05).实验组肝窦内皮细胞结构破坏及炎性细胞浸润程度均较对照组明显减轻.结论 VEGF能明显改善大鼠部分肝移植术后肝功能.这可能与其减轻肝窦内皮细胞损害和炎性细胞浸润程度有关.     

线粒体途径在缺血后处理减轻大鼠肝脏缺血再灌注损伤作用中的机制研究

目的 研究缺血后处理(IPO)减轻大鼠肝脏缺血再灌注损伤(IRI)的机制中关于线粒体途径发挥的作用.方法 按随机数字表法将SD大鼠分为3组,IRI组和IPO组建立肝移植模型,IRI组受鼠在供肝植入后,立即开放门静脉恢复血液供应 ;IPO组受鼠在门静脉完全开放前行IPO,即对门静脉行开放60 s、夹闭60 s,共重复6次.假手术组大鼠在开腹后仅游离肝周韧带,未进行肝移植.术后6 h(IRI组和IPO组为血流完全开放后6h,下同),取各组受鼠的血液和肝组织样本,检测肝功能,采用逆转录聚合酶链反应法检测肝组织B淋巴细胞因子-2(Bcl-2)mRNA和Bcl-2共存蛋白质(Bax) mRNA的表达,采用蛋白质印迹法检测肝组织细胞色素C(Cyt-c)蛋白的表达,使用流式细胞仪检测肝组织的细胞凋亡与坏死率及线粒体跨膜电位的变化,电镜下观察肝细胞线粒体的超微结构.结果 与假手术组相比,IRI组和IPO组肝功能明显受损(P＜0.05),肝组织Bax mRNA的表达明显上调(P＜0.05),Bcl-2 mRNA的表达明显下降(P＜0.05),Cyt-c蛋白含量显著升高(P＜0.05),肝组织细胞凋亡坏死率明显增加(P＜0.05),肝细胞线粒体跨膜电位明显下降(P＜0.05).而IPO组以上各项指标的改变均较IRI组明显减轻(P＜0.05),肝细胞线粒体的形态结构改变也明显改善.结论 IPO可能通过抑制线粒体途径来减轻大鼠肝移植中肝脏的IRI.     

TAT-血红素氧合酶-1融合蛋白对原位肝移植术大鼠肝细胞凋亡的影响

目的 评价TAT-血红素氧合酶-1(TAT-HO-1)融合蛋白对原位肝移植术大鼠肝细胞凋亡的影响.方法 健康成年雄性SD大鼠,体重250 ～ 280 g,作为肝移植术的供体和受体.参照文献构建TAT-HO-1融合蛋白(1 mg/ml).采用二袖套法建立大鼠原位肝移植术模型.将受体大鼠随机分为2组(n=24):对照组(C组)和融合蛋白组(TAT-HO-1组).C组和TAT-HO-1组分别于肝移植术毕静脉注射生理盐水、TAT-HO-1融合蛋白10 ml/kg.于无肝期前即刻(T0)、肝脏移植术后1h、6h和12 h(T1～3)时,分别取动脉血样,检测血清谷丙转氨酶(ALT)活性及透明质酸(HA)浓度;取肝组织标本,采用免疫组化法检测HO-1表达水平,采用TUNEL法检测凋亡细胞,计算凋亡指数.结果 与C组比较,TAT-HO-1组T1-3时HO-21表达上调,血清ALT、HA水平及肝实质细胞和肝窦内皮细胞凋亡指数降低(P＜0.05).结论 大鼠原位肝移植术后静脉注射TAT-HO-1融合蛋白可转导进入移植肝脏细胞,通过减轻肝细胞和肝窦内皮细胞凋亡,对肝移植术后的肝脏功能发挥保护作用.     

经典原位肝移植术中逆灌注法对移植肝缺血再灌注损伤的影响

目的 探讨经典原位肝移植术中逆灌注法对移植肝缺血再灌注损伤的影响.方法 35例经典原位肝移植患者随机分为试验组和对照组.试验组17例,采用经下腔静脉逆灌注法,在吻合门静脉前先开放下腔静脉,然后再吻合门静脉、肝静脉;对照组18例,采用常规经门静脉正向灌注法,先开放门静脉,再开放下腔静脉,然后吻合肝动脉.分别测定两组的以下指标:复温缺血时间(RWIT);移植术后1h及术后1、2、3、5、7天血清丙氨酸转氨酶(ALT)、谷氨酰转肽酶(GGT)、总胆红素(TB)、凝血酶原时间(PT);无肝期结束后2h下腔静脉血中的肿瘤坏死因子-α(TNF-α)和白细胞介素-1(IL-1)的浓度;无肝期结束后3h取肝组织活检行光镜检查,高倍镜下计算肝细胞水变性及坏死细胞百分比.结果 试验组的RWIT显著短于对照组(P＜0.05);术后1小时,术后1、2天试验组TB显著低于对照组(P＜0.05),术后3、5、7天两组无差异(P＞0.05);术后1、2天试验组ALT显著低于对照组(P＜0.05),术后1h、术后3、5、7天两组无差异(P＞0.05);术后1h,术后1、3天试验组GGT显著低于对照组(P＜0.05),术后2、5、7天两组无差异(P＞0.05);两组PT术后无差异(P＞0.05);无肝期结束后2h,试验组下腔静脉血中TNF-α,IL-l的浓度显著低于对照组(P＜0.05);病理组织学检查显示试验组肝细胞缺血再灌注损伤较对照组轻;无肝期结束后3h,试验组肝细胞水变性及坏死细胞百分比显著低于对照组(P＜0.05).结论 经典原位肝移植术中逆灌注法可减轻移植肝缺血再灌注损伤,改善移植肝早期肝功能.     

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.     

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.     

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.     

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.     

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.