大鼠肝肾联合移植供体DC细胞迁移诱导的免疫保护作用

目的探讨供体DC细胞迁移对肝肾联合移植免疫保护的诱导作用及机制。方法60只大鼠肝肾联合移植免疫排斥模型(选择DA大鼠为供体,Lewis大鼠为受体),随机分为3组：A组：白细胞介素(IL)-10处理的DC细胞干预组；B组：未经IL-10处理的DC细胞干预组；C组：空白对照组。利用所建立的大鼠肝肾联合移植模型结合成熟前期DC细胞进行研究,首先进行供体大鼠DC细胞的预先分离、培养和IL-10处理,然后输入肝肾联合移植后的受体大鼠体内,分析其对肝、肾移植物的免疫保护以及其对移植物和受体存活时间的影响。结果A组肝肾移植的急性排斥反应受到明显的抑制,平均存活(20．0±2．6)d；B组和C组均表现为典型的重度急性排斥反应,存活时间分别为(6．7±0．8)和(7．5±0．5)d；A组与B、C两组受体的累积生存率差异有统计学意义(P＜0．05)。结论IL-10预处理的DC细胞可以对大鼠肝肾联合移植中的移植物起到免疫保护作用；供体的成熟前期DC细胞迁移到受体组织内,能够抑制肝肾联合移植急性排斥反应,并延长肝、肾移植物和受体大鼠存活时间。     

1O-羟基喜树碱和环孢素A诱导异基因大鼠心脏移植受者免疫耐受的实验研究

目的以中药制剂10-羟基喜树碱(HCPT)和环孢素A(CsA)诱导异基因大鼠心脏移植受者免疫耐受,并探讨免疫耐受的特异性和形成机制.方法以纯系SD大鼠为供者,纯系Wis-tar大鼠为受者行异体颈部心脏移植.将移植后50只受者大鼠随机分成5组,分别接受不同剂量HCPT、CsA或二者联合应用.A组接受安慰剂.B组接受HCPT 1.0mg·kg-1·d-1,腹腔注射.C组接受HCPT 2.0 mg·kg-1·d-1,腹腔注射.E组接受CsA10.0 mg·kg·d-1,导管灌胃.F组联合应用HCPT和CsA,方法剂量同B组和E组.心脏移植物长期存活受者术后60 d停用免疫抑制剂,120 d同时行供者来源(SD)大鼠和无关供者(SHR)大鼠皮肤移植.结果3只C组大鼠和5只F组大鼠心脏移植术后停用免疫抑制剂长期存活超过730 d.8块SD大鼠皮肤移植物长期存活超过610 d,而8块SHR大鼠皮肤均被排斥,平均存活时间(4.50±1.25)d.结论大剂量HCPT或小剂量HCPT与CsA联合应用可诱导异基因大鼠心脏移植受者免疫耐受,且形成的免疫耐受具有明确的抗原特异性.     

门静脉预输注供者凋亡骨髓细胞延长大鼠移植心脏的存活时间

目的探讨门静脉输注供者的凋亡骨髓细胞对大鼠移植心脏存活时间的影响。方法以Wistar大鼠为供者、SD大鼠为受者,将其随机分为4组,每组15只,A组为对照组,受者术前6d经门静脉输注RPMI1640培养基0.5ml,术后不注射环孢素A(CsA);B组为骨髓细胞输注组,受者术前6d经门静脉输注供者的骨髓细胞5×107个,术后不用CsA;C组为凋亡细胞输注组,受者术前6d经门静脉输注供者的凋亡骨髓细胞5×107个,术后不用CsA;D组为CsA组,受者术前3d起腹腔注射CsA5mg/kg,直至术后10d。60Coγ射线照射诱导骨髓细胞凋亡,各组大鼠建立腹部异位心脏移植模型。观察各组移植心的存活时间、组织病理学改变,测定受者血清中白细胞介素10(IL-10)及转化生长因子β1(TGF-β1)的含量及单向混合淋巴细胞培养(MLR)结果。结果C组移植心的存活时间为(14.00±0.95)d,较A组明显延长(P<0.01),但仍未达到长期存活(存活时间短于CsA组)。术后7d,C组移植心组织切片呈现中度急性排斥反应,心肌细胞损害不明显,但有大量淋巴细胞浸润。除术后7d的TGF-β1外,C组其它各测定时点的血清IL-10及TGF-β1均高于其它3个组。C组大鼠的脾细胞在供鼠脾细胞的刺激下,细胞增殖反应明显低于A组、B组(P<0.01),而对第三品系大鼠的脾细胞仍有较强的增殖反应,具有明显的抗原特异性;CsA组的细胞增殖均被抑制。结论门静脉预输注供者的凋亡骨髓细胞,可明显延长大鼠移植心脏的存活时间,但单纯单剂量的输注凋亡细胞并不足以建立长期、稳定的免疫耐受。     

IL-12/STAT4途径激活对同种部分肝移植排斥反应的影响

目的　探讨白细胞介素 12 /信号传导子及转录激活子 (IL 12 /STAT4)信号途径激活在同种部分肝移植排斥中的作用。方法　将供者SD大鼠与受者LEW大鼠随机分为 4组 ,每组供、受者各 40只。A组 :全肝移植组 ;B组 :部分肝移植组 ;C组 :部分肝移植 IL 12硫代修饰反义寡脱氧核苷酸 (ASPODN )治疗组 ;D组 :部分肝移植 IL 12硫代修饰正义寡脱氧核苷酸 (SPODN)对照治疗组。观察移植肝排斥病理以及受者存活时间。分别采用Western blot及EMSA检测肝移植后 0h和4d移植肝IL 12蛋白表达、STAT4蛋白表达及其DNA结合活性 ;ELISA检测受者血清IL 2、IL 10及IFN γ水平。结果　B组和D组移植肝于移植后 4d出现排斥反应 ,早于A组和C组。B组受者存活时间 (13 .5± 0 .48)d ,较A组存活时间 (2 2 .6± 0 .59)d明显缩短 (P <0 .0 0 1) ;C组存活时间 (56.8±2 .5)d ,明显长于A组和B组 (P <0 .0 0 1)。肝移植后 4d ,移植肝IL 12、STAT4蛋白表达及其DNA结合活性、受者血清IL 2、IL 10和IFN γ水平 ,B组较A组明显增高 (P <0 .0 0 1) ,C组较B组明显降低 (P <0 .0 0 1) ,D组各项指标与B组相似。结论　IL 12 /STAT 4信号途径激活可能是同种部分肝移植免疫排斥发生的重要机制     

未成熟树突状细胞诱导大鼠免疫低反应性

目的观察供者来源的未成熟树突状细胞(imDCs)联合骨髓移植(BMT)对大鼠移植肾的保护作用,并探讨其机制.方法DA(RT1a)大鼠为供者,Lewis(RT11)大鼠为受者,Wistar大鼠为无关第三品系.将实验动物随机分为5组,每组8只,进行不同的预处理后进行肾移植.(1)阴性对照组受者不接受任何预处理;(2)imDCs诱导组受者术前7d经尾静脉注射经60Co照射(30 Gy)灭活的、供者来源的未成熟树突状细胞2×107/只;(3)BMT诱导组受者术前4 d经尾静脉注射供者来源的新鲜骨髓细胞2×108/只;(4)imDCs+BMT联合诱导组受者术前7 d经尾静脉注射经60Co照射(30 Gy)灭活的、供者来源的未成熟树突状细胞2×107/只,术前4 d经尾静脉注射供者来源的新鲜骨髓细胞2×108/只;(5)第三品系组预处理与imDCs+BMT联合诱导组相同,但供者肾脏来自Wistar大鼠.术后进行单向混合淋巴细胞反应(MLR);白细胞介素2(IL-2)逆转实验;体内细胞转移实验(DTH);流式细胞仪检测RT1a阳性细胞百分率.结果各组大鼠肾移植后平均存活时间分别为阴性对照组(7.12±1.25)d;imDCs诱导组(24.38±3.20)d;BMT诱导组(7.87±2.10)d;第三品系组(6.63±1.06)d;而imDCs+BMT联合诱导组延长到(80.75±16.88)d;后者与上述4组比较,差异均有统计学意义(P＜0.01).免疫耐受的大鼠脾细胞增殖程度(SI值,3.41)明显低于对照组(7.56),P＜0.01;转移耐受的Lewis大鼠(FI值,0.55)明显低于对照大鼠(0.93),P＜0.01;在免疫耐受的受者体内检测到RT1a阳性细胞.结论术前输注供者来源的未成熟树突状细胞联合骨髓移植,可成功诱导受者产生免疫耐受,显著延长肾移植大鼠的存活时间.可能机制为特异性T细胞克隆无能、T细胞的负向免疫调节以及嵌合体的形成.     

转染IL-12p35siRNA的供者树突状细胞延长大鼠移植小肠的存活时间

目的探讨转染IL-12p35siRNA的供者树突状细胞(DC)对大鼠移植小肠存活时间的影响。方法在体外以IL-12p35siRNA转染Wistar大鼠骨髓来源的DC,用逆转录聚合酶链反应测定转染细胞IL-12p35mRNA的表达,进行混合淋巴细胞反应,观察DC对SD大鼠T淋巴细胞的刺激作用。制作Wistar大鼠到SD大鼠的节段小肠异位移植模型,转染组小肠移植前7 d经阴茎背静脉给受者注射转染IL-12p35siRNA的DC 4×106个/只;未转染组移植前7 d注射未转染的DC 4×106个/只;对照组注射生理盐水。术后观察受者的存活时间,移植小肠进行组织病理学检查,应用酶联免疫吸附试验检测受者血清中白细胞介素2(IL-2)和γ干扰素(IFN-γ)的水平。结果DC转染IL- 12p35siRNA后,IL-12p35mRNA的表达明显降低,其刺激T淋巴细胞增殖的能力降低(P<0.01)。转染组受者小肠移植后的存活时间为(16.63±3.38)d,明显长于对照组和未转染组(P<0.01);转染组移植小肠组织中仅有炎症细胞浸润、黏膜层肿胀,绒毛腺体结构和肌层破坏程度较对照组和未转染组明显减轻;术后第10天,转染组的血清IL-2浓度为(175.8±11.5)ng/L,IFN-γ浓度为(70.6±7.2)ng/L,均显著低于对照组和未转染组(P<0.05)。结论转染IL-12p35siRNA,在体外可减轻DC对T淋巴细胞的刺激作用,在体内可抑制大鼠小肠移植后的排斥反应,延长移植小肠的存活时间。     

耐受性树突状细胞延长大鼠移植脾存活时间

目的 观察供者来源的耐受性树突状细胞（DC）在脾移植中的作用，并探讨其作用机理。方法 以Wista大鼠为供者，SD大鼠为受者，建立同种颈部异位脾脏移植模型。（1）分离供者的骨髓细胞，分别采用白细胞介素4（IL-4）和白细胞介素10（IL-10）诱导培养出成熟的DC和耐受性DC，并在光镜下观察两者的细胞形态学差别。采用流式细胞术检测两者对共刺激分子CD86表达的差异，采用混合淋巴细胞反应比较其在体外刺激同种异体T淋巴细胞增殖的反应能力。（2）将受者随机分成4组，每组10只。单纯移植组：受者不经任何预处理仅进行脾移植。IL-10DC组：在移植前7d经受者尾静脉注射2×10^6／ml的经IL-10诱导的DC 1 ml。IL-4 DC组：在移植前7d经受者尾静脉注射2×10^6／ml的经IL-4诱导的DC 1 ml。空白对照组：在移植前7d经受者尾静脉注射无细胞的培养液1ml。观察各组移植术后发生急性排斥反应的时间。结果 （1）经IL-10诱导的骨髓细胞表现为未成熟树突状细胞的形态和特性，细胞体积大，但少见树突状突起，细胞表面低表达CD86分子，不能有效刺激T淋巴细胞的增殖。而经IL-4诱导的骨髓细胞为典型的成熟树突状细胞，细胞胞体大，并有树突状突起，细胞表面高表达共刺激分子CD86，可显著刺激T细胞的增殖。（2）IL-10 DC组发生急性排斥反应的时间较其他3组明显延迟（P〈0．01）；IL-4 DC组发生急性排斥反应的时间较单纯移植组和空白对照组明显提前（P〈0．05）；而单纯移植组与空白对照组间则无明显差异（P〉0．05）。结论 应用供者来源的耐受性树突状细胞能够延缓大鼠移植脾急性排斥反应的发生时间。     

输注转染FasL基因的供者树突状细胞减轻小鼠心脏移植排斥反应

目的 探讨转染FasL基因的供者树突状细胞(DC)对小鼠心脏移植排斥反应的影响.方法 分离并培养C57BL/6小鼠骨髓DC,然后采用脂质体法以自行构建的pTracer-FasL真核表达质粒转染DC.以C57BL/6小鼠为供者,Balb/c小鼠为受者,将其分为转染组(n=12)、未转染组(n=12)及移植对照组(n=12).转染组小鼠心脏移植前7 d经阴茎背静脉注射1×106个转染FasL基因的供者DC;未转染组小鼠心脏移植前7 d经阴茎背静脉注射1×106个未转染的供者DC;移植对照组仅行心脏移植,不接受供者DC输注.供心均移植于受者腹腔内.各组中,6只小鼠用于观察移植心脏存活时间,另6只于术后7 d处死,取移植心脏,进行组织学观察及移植心脏排斥反应病理分级.结果 转染组、未转染组和移植对照组小鼠移植心脏存活时间的中位数分别为20 d、8.5 d和9 d,转染组移植心脏的存活时间明显长于未转染组和移植对照组(P＜0.01).转染组中,2只排斥反应的病理分级为0级,4只为1级;未转染组中,2只为2级,4只为3级;移植对照组中,1只为2级,5只为3级.转染组排斥反应的病理分级明显低于移植对照组(P＜0.01).结论 受者于心脏移植前输注转染FasL基因的供者DC,可有效延长移植心脏的存活时间,并减轻排斥反应的程度.     

转染IL-12亚基干扰RNA的供者树突状细胞延长同种小鼠移植心脏存活时间

目的探讨预输注转染白细胞介素12p35亚基干扰RNA(Ib-12p35siRNA)的供者来源树突状细胞对移植心脏存活时间的影响。方法制备供者BALB/c小鼠骨髓来源的树突状细胞,培养7d后,根据实验设计,分别以携带IL-12p35siRNA或HKsiRNA的重组腺病毒载体转染树突状细胞。移植前7d,经受者C57BL/6小鼠尾静脉注射转染IL-12p35siRNA的树突状细胞(p35组)和转染HKsiRNA的树突状细胞(HK组),并设未转染的对照组(未转染组),然后进行供、受者间的异位(颈部)心脏移植。术后观察移植心脏的存活情况,术后第14d采取静脉血,以酶联免疫吸附试验测定血清中自细胞介素2(IL-2)、IL-4、IL-10和γ干扰素(INF-γ)的水平。结果术后未转染组移植心脏的存活时间为(7．83±1．61)d,HK组为(7．17±1．60)d,p35组移植心脏存活时间明显延长,为(20．17±2．71)d,与HK组和未转染组相比,差异有统计学意义(P＜0．01)。p35组IL-2和INF-γ的水平明显低于HK组和未转染组(P＜0．01),而IL-4和IL-10的水平明显高于HK组和未转染组(P＜0．01)。结论预输注转染IL-12p35siRNA的供者树突状细胞能延长同种小鼠移植心脏的存活时间。     

供者脾细胞和环磷酰胺联合预处理对移植心脏存活的作用

目的　诱导同种异体心脏移植的免疫耐受 ,为心脏移植的抗排斥反应治疗提供依据。　方法　采用供者脾细胞和环磷酰胺联合预处理受者 ,诱导受者对移植心脏的免疫耐受 ,然后行大鼠颈部心脏移植术。将实验动物分成 5组。对照组 :受者不作任何预处理 ;组 1:预处理第 2天用环磷酰胺 5 0～ 80 mg/ kg预处理受者 ;组 2 :预处理当天用供者 5～ 10× 10 7个脾细胞预处理受者 ;组 3:受者不作任何预处理 ,手术当天开始用环孢菌素 A10 mg/ kg,每 2天 1次 ,共 8～ 10次 ,腹腔内注入 ;组 4:预处理当天用供者脾细胞 5～ 10× 10 7个和第 2天环磷酰胺 5 0～ 80 mg/ kg联合预处理受者。　结果　各组移植心脏的存活时间明显不同 ,5组移植心脏的存活时间差异有显著性 (P<0 .0 1)。供者脾细胞和环磷酰胺预处理受者的移植心脏存活时间明显延长。　结论　供者脾细胞和环磷酰胺联合预处理 ,可诱导受者对移植心脏的免疫耐受。     

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.