活体红色荧光成像评估Ag85A／BDNA疫苗联合抑瘤效应的实验研究

目的：探讨可视、直观评估Ag85A／BDNA疫苗联合抑瘤效应的科学方法。方法：采用红色荧光蛋白基因DsRed—Express标记小鼠膀胱癌细胞BTT739,经G418抗性筛选获得稳定表达RFP的细胞克隆BTT739-RFP,将BTT739～RFP细胞接种到615小鼠皮下,建立可视化膀胱癌移植瘤模型。将建模成功的32只小鼠随机分为pVAX1-Ag85A／B联合组：BCG组;空白质粒（pVAX1）;生理盐水（NS）。建模后第7、14、21天注射相应的药物。分别于给药前即第7和第28天进行活体荧光成像,进行统计学处理。并于第28天检测血清特异性抗体水平和脾淋巴细胞的增殖活性。结果：构建了稳定表达RFP的BTT739细胞;成功建立可视化膀胱癌模型,成瘤率100％;经治疗后,pVAX1-Ag85A／B组的荧光强度明显低于pVAX1组和NS组,与BCG组无统计学差异。pVAX1-Ag85A／B组的抗体滴度为1：1000,BCG免疫组的抗体滴度为1：800。pVAX1-Ag85A／B组和BCG组均可提高淋巴细胞增殖活性,二者差异无统计学意义。结论：应用Ag85A／BDNA疫苗可提高膀胱癌小鼠的免疫功能,其效果与BCG差异无统计学意义;活体红色荧光体外成像的评估体系与细胞水平的分析一致。     

逆转录病毒介导HSV-TK基因结合更昔洛韦对裸鼠膀胱癌模型的抑癌作用

目的研究利用逆转录病毒介导单纯疱疹病毒胸苷激酶(HSVTK)基因结合抗病毒药更昔洛韦(GCV)对裸鼠膀胱癌模型的治疗作用。方法构建HSVTK基因逆转录病毒重组体,转染PA317包装细胞后获得相应病毒,分3组进行动物实验。A组7个肿瘤,膀胱癌细胞MBT2种植小鼠皮下形成裸鼠动物模型,用带HSVTK基因的逆转录病毒瘤内注射并腹腔内注射GCV。B组6个肿瘤,用转导HSVTK基因的膀胱癌细胞形成裸鼠膀胱癌模型并腹腔内注射GCV。C组6个肿瘤,用膀胱癌细胞MBT2种植小鼠皮下形成裸鼠膀胱癌模型,并注射生理盐水。比较3组治疗后10d、20d肿瘤的体积变化情况。结果GCV治疗10d后,A、B和C组肿瘤平均体积分别为(55.37±4.52)、(49.77±4.15)、(146.27±10.46)mm3,A、B组与C组比较差异有统计学意义(P<0.01),A、B组间差异无统计学意义(P>0.05)。20d后A、B和C组肿瘤平均体积分别为(186.75±8.14)、(72.50±6.70)、(441.76±41.80)mm3,3组间两两比较差异均有统计学意义(P<0.01)。结论利用逆转录病毒介导HSVTK基因结合GCV治疗可显著抑制裸鼠膀胱癌的生长,并使肿瘤获得部分消退。     

分枝杆菌Ag85B与膀胱癌的治疗

Ag85B是分枝杆菌最主要的分泌蛋白,能够诱导机体强烈的Th1免疫反应,并在分枝杆菌细胞壁合成中发挥重要作用,还具有与纤维粘连素(FN)结合的特性。Ag85B蛋白能够诱导膀胱癌患者PBMC的增殖反应,并能诱导Th1细胞分泌细胞因子IFN-γ和IL-2;Ag85B基因修饰的膀胱肿瘤细胞疫苗具有抗膀胱肿瘤效应;利用Ag85B的外分泌特性构建分泌细胞因子的BCG在治疗膀胱癌方面可能更具有优势;Ag85B基因编码的DNA疫苗为膀胱癌的基因免疫治疗提供了新的思路。     

Ag85A与Ag85BDNA疫苗联合免疫对可移植性鼠膀胱肿瘤的免疫调节效应

目的探讨联合应用Ag85A与Ag85BDNA疫苗抗膀胱肿瘤的免疫效应。方法采用小鼠膀胱癌BTT739细胞株,构建可移植性T739小鼠膀胱肿瘤模型。随机法分为6组：生理盐水组、BCG组、pcDNA3．1＋组、pcDNA—Ag85A组、pcDNA-Ag85B组及pcDNA—Ag85A和pcDNA-Ag85B联合组。荷瘤后第7天、14天和21天各肌注1次,末次注射后第7天检测各组小鼠脾脏的CD4＋和CD8＋T细胞亚群数量及CD4＋／CD8＋比值、小鼠血清IFN-γ、肿瘤体积重量并进行组织病理学检查。结果Ag85A与Ag85BDNA疫苗联合免疫组CD4＋和CD8＋T细胞亚群数量及CD4＋／CD8＋比值、血清IFN-γ明显高于DNA疫苗单独免疫组;小鼠的肿瘤重量明显低于DNA疫苗单独免疫组,差异有显著性（P〈0．05）;肿瘤组织病理学分析Ag85A与Ag85BDNA疫苗联合免疫组肿瘤坏死较DNA疫苗单独免疫组明显,且瘤体周围及瘤体内炎性细胞浸润较多。但Ag85A与Ag85BDNA疫苗联合、pcDNA—Ag85A、pcDNA—Ag85BDNA疫苗单独应用组均不及单纯应用BCG的免疫调节效应。结论Ag85A与Ag85BDNA疫苗联合免疫在抗膀胱肿瘤过程中具有明显的免疫效应,明显优于DNA疫苗单独免疫,二者联用具有协同增强免疫效应;但Ag85A与Ag85BDNA疫苗联合免疫效应尚达不到BCG的作用。     

高压氧对人前列腺癌LNCaP细胞株小鼠荷瘤模型作用的研究

目的:评估应用高压氧治疗前列腺癌放疗后出血性膀胱炎的安全性,探讨高压氧对体内前列腺癌细胞生长的影响。方法:采用人前列腺癌LNCaP细胞株皮下接种构建小鼠荷瘤模型(n=30),随机分为对照组(n=15)和实验组(n=15)。对照组常压常氧条件下饲养,实验组每周进行5次0.2MPa高压氧暴露,共计20次。连续观察4周两组移植瘤生长体积的变化,应用免疫组化法比较两组瘤体组织相关病理学特征指标:瘤体微血管密度(CD34)、瘤细胞增殖(Ki-67蛋白)以及瘤细胞凋亡(p53、p27蛋白)。结果:肿瘤接种后第28天,对照组移植瘤体积为(122.0±8.2)mm3,实验组为(120.0±7.9)mm3,两组差异无显著性(P>0.05);对照组移植瘤CD34及Ki-67、p53、p27蛋白表达的阳性细胞率分别为(36.2±4.9)%、(75.3±8.4)%、(44.2±5.7)%、(61.5±5.5)%,实验组分别为(39.3±5.2)%、(78.1±7.6)%、(40.4±6.2)%、(63.7±5.1)%,病理学特征均无显著性差异(P>0.05)。结论:高压氧对小鼠荷瘤模型前列腺癌细胞生长无促进作用,对前列腺癌中新生血管也无明显影响。     

肺纤维化对大鼠阴茎勃起功能的影响

目的:研究肺纤维化对大鼠勃起功能的影响及其机制。方法:12周雄性SD大鼠40只,随机分为4组:正常对照4周组(A组)、6周组(B组)和肺纤维化大鼠4周组(C组)、6周组(D组)各10只,分别用生理盐水(A、B组)及博莱霉素(5 mg/kg)气管内注入,饲养4周(A、C组)、6周(B、D组)后,测定大鼠血清睾酮、动脉血气分析、阴茎海绵体内压/平均颈动脉压(ICP/MAP),取阴茎标本测定NOS活性及cGMP含量,实时荧光PCR检测eNOS、iNOS和nNOS的mRNA在阴茎海绵体的表达,W estern印迹检测阴茎海绵体eNOS蛋白的表达。结果:电刺激的3 V,5 V C组ICP/MAP×100(16.37±2.19,27.19±3.18)较A组(30.78±2.66,50.09±6.97)显著降低(P<0.05),D组ICP/MAP×100,3 V,5 V(10.17±1.31,17.40±1.74)较B组(31.45±3.07,51.23±7.23)显著降低(P<0.05),D组ICP/MAP×100值较C组显著降低(P<0.05)。C组PaO2(75.50±13.87)mmHg较A组(103.80±6.88)mmHg显著降低(P<0.05),D组PaO2(83.60±5.50)mmHg较B组(102.70±5.77)mHg显著降低(P<0.05)。C组血清睾酮水平(391.1±264.7)ng/d l较A组(175.9±53.0)ng/d l显著升高(P<0.05),D组血清睾酮水平(745.4±408.8)ng/d l较B组(177.8±52.3)ng/d l显著升高(P<0.05),同时D组血清睾酮水平较C组显著升高(P<0.05)。C组NOS活性及cGMP含量[(1.50±0.14)U/mg prot,(35.69±3.64)pmol/mg]较A组[(2.66±0.39)U/mg prot,(51.10±7.22)pmol/mg]显著降低(P<0.05),D组NOS活性及cGMP含量[(1.40±0.20)U/mg prot,(34.55±4.30 pmol/mg)]较B组[(2.75±0.36)U/mg prot,(52.15±6.86)pmol/mg]显著降低(P<0.05),C组与D组比较NOS活性及cGMP含量无显著性差异(P>0.05)。C组eNOS蛋白表达量(0.79±0.01)较A组(0.87±0.01)显著降低(P<0.01),D组eNOS蛋白表达量(0.71±0.02)较B组(0.88±0.01)显著降低(P<0.05),D组较C组eNOS蛋白表达量显著降低(P<0.05)。C组eNOS mRNA表达量(4.46±0.92)较A组(2.61±0.68)显著升高(P<0.05),D组eNOS mRNA(2.79±0.60)表达量与B组(2.69±0.65)无显著性差异(P>0.05),nNOS及iNOS的mRNA表达量在A、B组与C、D组间均无显著性差异(P>0.05)。结论:肺纤维化可通过抑制阴茎海绵体eNOS蛋白的表达、降低总NOS活性及cGMP含量等机制抑制阴茎勃起功能。     

pVAX1-Ag85B质粒的构建及其免疫原性的可视化研究

构建以Ag85B基因为基础的DNA疫苗,并用活体红色荧光成像探讨其在动物体内免疫原性。方法：以pET28a—Ag85B基因组DNA为模板,用PCR扩增获得Ag85B全长基因;将PCR产物构建成pUCm—Ag85B亚克隆;经限制性内切酶消化后克隆人pVAX1载体中构建pVAX1-Ag85B,酶切、DNA测序鉴定。并将构建的DNA疫苗经肌肉免疫可视化膀胱癌移植瘤模型,通过活体红色荧光成像,从整体上直接、可视地观测Ag85B的免疫原性。结果：经NheI和HindⅢ双酶切、DNA测序鉴定后证实,Ag85B基因定向克隆人pVAX1载体,碱基无突变,序列完全正确。免疫小鼠后,pVAX1-Ag85B组和BCG组均可提高淋巴细胞增殖活性,但效果不及卡介苗。结论：成功地构建了pVAX1-Ag85B质粒,为膀胱肿瘤的基因免疫治疗提供可靠的实验方法。免疫小鼠后,可提高膀胱癌小鼠免疫水平,但效果不及卡介苗。     

人参皂苷Rg1对七氟醚麻醉所致幼鼠远期认知功能障碍的保护作用及机制

目的 观察人参皂苷Rg1(ginsenoside Rg1,Rg1)对七氟醚麻醉所致幼鼠远期认知功能障碍的改善作用及其机制.方法 72只新生6日龄C57BL/6J小鼠采用随机数字表法分为4组(每组18只):对照+生理盐水组(Con+NS组)、对照+Rg1组(Con+Rg1组)、七氟醚麻醉+生理盐水组(Sev+NS组)、七氟醚麻醉+Rg1组(Sev+Rg1组).Sev+NS组和Sev+Rg1组分别在出生后6~8 d每天接受3%七氟醚+100%氧气麻醉2 h,Con+NS组及Con+Rg1组小鼠在相应日龄吸入相同时间100%氧气.麻醉前30 min各组分别进行生理盐水(1 ml·kg-1·d-1)或Rg1(10 mg·kg-1·d-1)腹腔注射.各组取12只小鼠于第31~37天行水迷宫实验,行为学测试结束后取海马行Western blot检测突触后密度蛋白95(postsynaptic density 95,PSD-95)含量,其余小鼠(每组6只)于第8天麻醉手术后即刻行ELISA检测海马ATP及活性氧簇(reactive oxygen species,ROS)水平.结果 与Con+NS组比较,Sev+NS组第35~37天水迷宫实验逃避潜伏期[(35.6±4.5)、(28.3±3.5)、(21.9±2.4)s比(45.7±8.1)、(41.9±8.8)、(35.1±12.4)s]明显延长(P<0.05),平台次数[4(8,2)次比2(6,0)次]明显减少(P<0.05),PSD-95水平[(100±6)%比(77±6)%]明显降低(P<0.05),ROS水平[(100±4)%比(121±11)%]明显升高(P<0.05),ATP水平[(100±6)%比(82±7)%]明显降低(P<0.05).Sev+Rg1组与Con+Rg1组比较,31~37 d水迷宫实验逃避潜伏期、 穿越平台次数、PSD-95水平、ROS水平及ATP水平差异均无统计学意义(P>0.05).结论 Rg1可改善七氟醚麻醉所致的幼鼠远期认知功能障碍,其机制可能与抑制氧化应激保护线粒体功能并增强突触可塑性有关.     

分枝杆菌Ag85B与膀胱癌的治疗

Ag85B是分枝杆菌最主要的分泌蛋白，能够诱导机体强烈的Th1免疫反应，并在分枝杆菌细胞壁合成中发挥重要作用，还具有与纤维粘连素(FN)结合的特性。Ag85B蛋白能够诱导膀胱癌患者PBMC的增殖反应，并能诱导Th1细胞分泌细胞因子IFN-γ和IL-2；AdB5B基因修饰的膀胱肿瘤细胞疫苗具有抗膀胱肿瘤效应；利用Ag85B的外分泌特性构建分泌细胞因子的BCG在治疗膀胱癌方面可能更具有优势；Ag85B基因编码的DNA疫苗为膀胱癌的基因免疫治疗提供了新的思路。     

HRZ三联抗结核药/TGF-β1 siRNA纳米脂质体对体外BCG感染的人巨噬细胞中Ag85A及TGF-β1表达的影响

目的:探讨异烟肼、利福平、吡嗪酰胺(HRZ)三联抗结核药/表皮转化生长因子(TGF)-β1 si RNA纳米脂质体对体外BCG感染的人巨噬细胞中Ag85A及TGF-β1表达的影响。方法:体外培养人单核细胞株THP-1诱导分化成巨噬细胞,分为4组,空白组为单纯巨噬细胞培养;模型组为巨噬细胞与卡介苗(bacillus calmetteguerin,BCG)以1∶5的比例共培养3h,制备BCG感染的巨噬细胞模型;对照组为BCG感染的巨噬细胞与HRZ三联抗结核药纳米脂质体共培养;实验组为BCG感染的巨噬细胞与三种不同浓度的HRZ三联抗结核药/TGF-β1 si RNA纳米脂质体(C1组为35mg/ml,C2组为40mg/ml,C3组为50mg/ml)共培养。采用RT-PCR检测各组人巨噬细胞中Ag85A及TGF-β1的mRNA表达量,Western-blot方法检测Ag85A及TGF-β1的蛋白表达量。结果:与空白组相比,模型组Ag85A和TGF-β1的m RNA及蛋白量表达明显上调(P0.05);对照组中Ag85A的mRNA及蛋白量和TGF-β1的mRNA水平与模型组相比明显下调(P0.05);实验组3种不同浓度(C1组、C2组、C3组)HRZ三联抗结核药/TGF-β1 si RNA纳米脂质体处理后,Ag85A和TGF-β1的mRNA及蛋白表达量与模型组和对照组相比进一步下调(P0.05),随着纳米脂质体浓度的增加,Ag85A和TGF-β1 m RNA及蛋白表达量有明显下降趋势,C1组与C3组相比Ag85A m RNA及蛋白表达量差异有统计学意义(P0.05);C1组与C2组、C3组相比TGF-β1 mRNA及蛋白量表达差异有统计学意义(P0.05);C2组与C3组相比Ag85A m RNA和TGF-β1蛋白表达量差异有统计学意义(P0.05)。结论:HRZ三联抗结核药/TGF-β1 si RNA纳米脂质体对体外BCG感染的人巨噬细胞具有明显的下调Ag85A基因表达作用及TGF-β1基因沉默作用。     

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.