代谢组学在脊柱结核血清诊断标志物筛选中的应用

目的分析脊柱结核(STB)患者血清代谢特征, 筛选潜在诊断生物标志物。方法收集2020年1月至2022年1月于宁夏医科大学总医院骨科确诊的25例STB患者作为实验组, 25例健康体检者作为对照组。应用超高效液相色谱串联四极杆飞行时间质谱技术检测两组血清中的代谢物, 结合两独立样本t检验等单变量统计分析方法和主成分分析、偏最小二乘判别分析等多元统计分析筛选STB患者血清中主要的差异代谢物, 并进行受试者工作特征曲线分析评估其诊断效能。结果共检测到4 755种代谢物, 实验组血清中差异表达的代谢物共有570种, 其中343种上调, 227种下调。生物信息分析结果显示, 差异代谢物主要富集在不饱和脂肪酸的生物合成、卟啉代谢、组氨酸代谢、β-丙氨酸代谢、泛酸和辅酶A的生物合成等通路。磷脂酰胆碱(O-13:0/O-1:0)、溶血磷脂酰乙醇胺[(18∶1(11Z)/0∶0)]、Palmitoleoyl-ethanolamine在实验组的含量均低于对照组(493.170比123.463, t=-6.390, P<0.01;239.196比14.708, t=-11.019, P<0.01...     

血清B细胞刺激因子及C3d结合型供者特异性抗体在肾移植术后慢性抗体介导排斥反应中的诊断价值

目的观察血清B细胞刺激因子(BAFF)与C3d结合型供者特异性抗体(DSA)在肾移植术后慢性抗体介导排斥反应(AMR)中的诊断价值。方法回顾性分析2010年5月至2012年5月于首都医科大学附属北京朝阳医院行同种异体肾移植术的109例受者资料,观察术后3年慢性AMR发生情况。病理诊断为慢性AMR的患者,留取诊断时刻静脉血5 m L;同时留取与慢性AMR患者同期行肾移植术、未发生慢性AMR的受者血样。检测血清BAFF值、群体反应性抗体(PRA)和DSA,PRA强阳性和DSA阳性者检测血清C3d结合型DSA。绘制BAFF和C3d结合型DSA受试者工作特征(ROC)曲线,计算灵敏度、特异度、约登指数及曲线下面积。P0.05为差异有统计学意义。结果 109例肾移植受者中,共19例病理诊断为慢性AMR,血样平均留取时间为术后(28±7)个月,同期手术且未出现慢性AMR的32例受者血样留取时间为术后(27±5)个月。慢性AMR患者和同期手术的非慢性AMR患者DSA阳性比例、C3d结合型DSA阳性比例和BAFF值分别为52.6%(10/19)和15.6%(5/32)、26.3%(5/19)和3.1%(1/32)、(2 070±825)pg/m L和(790±293)pg/m L,差异均有统计学意义(χ~2=43.59、6.18,t=23.745,P均0.05),PRA阳性比例两组差异无统计学意义。血清BAFF和C3d结合型DSA诊断慢性AMR的灵敏度、特异度、约登指数和ROC曲线下面积分别为83%和77%、79%和83%、0.62和0.60、0.78和0.79,ROC曲线下面积差异无统计学意义(P0.05)。结论血清BAFF和C3d结合型DSA对诊断肾移植术后慢性AMR有一定价值,可作为高危患者诊断慢性AMR的辅助手段。     

肾移植受者术后早期外周血树突状细胞亚群的动态变化及意义

目的 分析肾移植受者手术前后外周血中树突状细胞(DC)及其亚群骨髓源性DC(mDC)和浆细胞源性DC(pDC)的动态变化,探讨其与排斥反应的关系.方法 检测28例肾移植受者术前,术后1、7和28 d外周血中白细胞总数和单个核细胞数(PBMNC);应用流式细胞术测定DC及其亚群的数量和pDC/mDC.应用酶联免疫吸附试验法测定手术前后血清白细胞介素(IL)-10和IL-12水平.15名健康志愿者作为正常对照.结果 移植组术前外周血DC总数、pDC和mDC数量均低于对照组(P＜0.05),但两组pDC/mDC的差异无统计学意义(P＞0.05).移植组受者术后第1天外周血DC数量骤然降低,然后缓慢上升,第28天恢复至手术前的73.7％;mDC和pDC术后也降低,但mDC恢复较快,pDC恢复缓慢,至术后28 d分别达到术前水平的80.1％和50.1％(P＜0.05).术后第7天,移植组发生排斥反应者mDC数量高于未发生排斥反应者(P＜0.01).受者手术前后IL-10和IL-12的水平变化不明显.结论 DC及其亚群的变化与肾移植受者免疫状态有关,其变化异常提示受者免疫状态不稳定,在受者发生急性排斥反应时,可以作为诊断的参考指标.     

肾移植术后急性体液性排斥反应的治疗

目的 总结肾移植术后急性体液性排斥反应中针对HLA抗体的检测和处理经验.方法 肾移植受者15例,术前行HLA分型、交叉配型和群体反应性抗体(PRA)的检测,术后采用他克莫司(或环孢素A)、霉酚酸酯和糖皮质激素预防排斥反应.15例于肾移植后1～14 d发生抗体介导的急性排斥反应(AMR),采用抗胸腺细胞球蛋白(100 mg/d,使用5 d)治疗,或将环孢素A转换为他克莫司,当PRA明显升高,且血清中出现供者特异性HLA抗体时,即行血浆置换(PP),共行1～5次,每次PP后静脉输注免疫球蛋白(IVIG)100～150 mg/kg,最后1次PP后给予WIG 200～500mg/kg.结果 术后出现抗供者特异性HLA Ⅰ类抗体者9例,抗HLAⅡ类抗体者4例,同时出现抗Ⅰ、Ⅱ类抗体者2例.14例的AMR逆转,1例术后发生移植肾功能恢复延迟,彩色多普勒超声波显示移植肾血流灌注差,于术后第10天切除移植肾.并行二行肾移植.2例AMR后并发急性肾小管坏死,透析后移植肾功能恢复正常.抗排斥反应治疗期间患者均未发生严重感染.随访12～52个月,1例因慢性移植肾肾病恢复血液透析治疗,1例死于心血管疾病,其余患者移植肾功能稳定.结论 将ATG、PP和IVIG联合应用能有效逆转AMR.     

基于四级杆飞行时间质谱技术的大鼠急性胰腺炎尿液代谢组学

目的：应用四级杆飞行时间质谱的代谢组学技术,对大鼠在急性胰腺炎（AP）时尿液的变化特征及生物标记物进行分析。方法：将12只雄性大鼠平均分为模型组和对照组,采用由胆胰管逆行注射牛磺胆酸钠诱发的AP模型,造模后分置于代谢笼饲养,收集24 h尿液;运用高效液相色谱串联电喷雾四级杆飞行时间质谱（LC-ESI-Q-TOF-MS）技术,分别采用正谱与负谱模式扫描处理后的尿液样本,结合主成分分析（PCA）和偏最小二乘判别分析法（PLS-DA）研究两组尿液间主要代谢物质的差异。结果：两组大鼠尿液代谢轮廓图在正谱与负谱模式下均得到了良好的区分,发现了18个潜在的生物标志物。结论：基于四级杆飞行时间质谱技术的代谢组学研究方法分析尿液中的代谢物特征,可以将AP模型与对照组大鼠进行区分,是发现未知生物标志物的有效手段。     

新疆维吾尔族肾癌血清蛋白指纹图谱的建立

目的 筛选并建立新疆维吾尔族肾癌血清蛋白指纹图谱诊断模型. 方法 采用弱阳离子交换蛋白质芯片(CM10蛋白芯片)及表面增强激光解析电离飞行时间质谱(SELDI-TOF-MS)技术对45例维吾尔族肾癌患者和45例正常对照者血清指纹图谱进行检测,结果用ZUCI-蛋白芯片数据分析系统软件包进行分析,通过支持向量机运算建立区分肾癌蛋白指纹图谱诊断模型,留一法交叉验证作用评估模型,判别效果. 结果 两组血清中筛选出M/Z为4296、4305、5914、5935、6116、6887、8085、8142、8573共9个差异有统计学意义(P＜0.05)的标志蛋白,所建立的诊断模型诊断肾癌的灵敏性为100％ (45/45),特异性为91％ (41/45).进一步用50例未知血清标本盲法测试该模型,双盲验证后的灵敏性和特异性分别为93％ (28/30)和85％ (17/20). 结论 SELDI-TOF-MS结合支持向量机建立维吾尔族肾癌血清蛋白质指纹图谱模型具有较高的敏感性与特异性,值得进一步研究和应用.     

血清降钙素原检测对于肾移植术后肺部感染的诊断价值

目的：与内毒素和C反应蛋白（ CRP）检测结果进行比较,探讨血清降钙素原（ PCT）检测在肾移植术后肺部感染诊断中的临床意义及其应用价值。方法回顾性分析2010年2月至2013年9月武汉大学移植医学中心98例肾移植术后并发肺部感染的受者临床资料。根据肺部感染的病原体诊断标准将受者分为细菌组（48例）和非细菌组（50例）,比较PCT、内毒素和CRP检测3种方法诊断肾移植术后细菌性肺部感染的灵敏度和特异度,比较3种方法对确诊肾移植术后并发细菌性肺部感染受者的阳性诊断结果。结果 PCT 检测灵敏度为95.8％,特异度为94．0％;内毒素检测灵敏度为77．1％,特异度为72．0％;CRP检测灵敏度为52．1％,特异度为58．0％。血清PCT检测细菌组受者阳性结果高于内毒素和CRP检测（χ2＝7.36,10．04, P均＜0．05）。结论血清PCT检测对于肾移植术后细菌性肺部感染的临床诊断价值高于内毒素和CRP,可作为肾移植受者是否并发细菌性肺部感染的优选诊断指标。     

甲状腺激素水平与移植肾功能关系的临床研究

目的 探讨肾移植受者的血清甲状腺激素水平与移植肾功能的关系.方法 57例肾移植受者根据移植后肾功能恢复情况分为移植肾功能恢复延迟(DGF)组(7例)和稳定组(50例).检测两组术前及术后不同时间的血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)、促甲状腺素(TSH)和血清肌酐(Scr)水平.另检测30名健康志愿者的4项指标水平,作为正常对照.将稳定组术后第10天甲状腺激素水平与Scr水平进行相关性分析.结果 稳定组和DGF组术前血清T3、T4水平低于对照组(P＜0.01),而两组术前TSH水平与对照组相比较,差异无统计学意义(P＞0.05).稳定组与DGF组间术前各指标的差异无统计学意义(P＞0.05).稳定组术后第1天T3较术前下降约30％(P＜0.05),下降幅度大于其他指标,直到术后1周开始上升,术后2周接近正常水平,术后3周时已高于术前(P＜0.01);T4术后早期降低,10d后呈上升趋势,术后3周才接近术前水平;术后各时间段TSH水平与术前相比较,差异均无统计学意义(P＞0.05);Scr于术后7d恢复至正常水平.DGF组T3于术后21 d达到正常水平,T4于术后30 d达到术前水平;Scr于术后30 d达到正常水平.术后第10天,稳定组受者血清T3与Scr呈负相关(相关系数=0.546,P＜0.01),T4与Scr呈负相关(相关系数=0.423,P＜0.01).TSH与Scr无相关性.结论 T3、T4水平与移植后肾功能有相关性,要重视肾移植受者术后早期甲状腺功能状态及对受者恢复的影响.     

供者特异性抗体监测在肾移植中的应用

目的 研究肾移植术后受者血清中供者特异性抗体（DSA）与发生急性排斥反应的关系,为临床早期诊断、合理制定个体化治疗方案、评估疗效提供客观的参考依据.方法 选取2012年1月至2013年8月西安交通大学医学院第一附属医院肾病医院肾移植科285例首次肾移植受者,术后动态监测DSA水平,检测时间点为术后3,5,7,14,21,30,60,90 d.观察受者肾功能和急性排斥反应发生情况.使用卡方检验或Fisher精确概率法比较不同HLA抗体类型的受者急性排斥反应发生率.结果 285例肾移植受者术后初筛人类白细胞抗原（HLA）抗体阳性率为22.11％ （63/285）,其中DSA阳性4例.急性排斥反应发生率6.67％ （19/285）.HLA抗体阴性受者和HLA抗体阳性且DSA阴性受者急性排斥反应发生率分别为3.15％ （7/222）和16.95％ （10/59）,二者相比差异有统计学意义（x2=12.891,P＜0.05）;4例DSA阳性受者有3例发生急性排斥反应,与HLA抗体阴性、HLA抗体阳性且DSA阴性受者急性排斥反应发生率相比,差异均有统计学意义（P=0.000和P=0.016）.19例发生急性排斥反应受者经甲泼尼龙、兔抗人胸腺细胞免疫球蛋白冲击治疗或血浆置换等治疗后,15例受者成功逆转,1例死于并发症.结论 动态监测肾移植术后受者DSA水平,可预测移植肾功能状态,对急性排斥反应的发生有重要预警作用,有利于及时清除或降低DSA水平,对有效预防和及时诊治排斥反应具有重要作用。     

肝细胞癌潜在血清标志物GRO-1和Thrombin的蛋白鉴定及其临床特征分析

目的 寻找自效的早期诊断及判断肝细胞癌(HCC)预后的血清标志物.方法 利用表面增强激光解吸离子化-飞行时间质谱(SELDI-TOF-MS)技术确定HCC患者血清蛋白表达谱.对HCC 81例、肝炎82例和健康志愿者80例血清标本蛋白表达谱进行比较,经高效液相色谱分离和质谱鉴定蛋白质序列.另取48例HCC、54例肝硬化、62例大肠癌、55例鼻咽癌、36例肺癌和42例健康志愿者血清,利用PS20免疫芯片和SELDI技术对候选标志物进行验证.荧光定量PCR技术检测55例HCC患者癌和癌旁组织,13例正常肝组织中候选标志物基因的表达情况,探讨它们与HCC患者临床预后的相关性.结果 检出两个HCC候选标志物凝血酶轻链(Thrombin light chain)和生长相关性癌基因编码蛋白(GRO-1).以这两个因子建立的HCC诊断模型敏感性和特异性均为89.6％,显著高于甲胎蛋白(AFP)单独检测敏感性和特异性(69％,83％).它们与AFP联合使用后的灵敏度和特异度更高(91.7％,92.7％),而对大肠癌、鼻咽癌、肺癌的敏感性均不超过50％.HCC 患者癌组织的GRO-1与Thrombin的表达具有显著相关性(r=0.73,P＜0.01),GRO-1表达与肝外转移及术后复发显著相关(P＜0.05),Thrombin的表达量与术后复发及AFP升高相关(P＜0.05).GRO-1和Thrombin高表达的患者术后5年生存率明显低于GRO-l低表达的患者.GRO-1表达量是影响HCC预后的独立影响因素.结论 Thrombin light chain和GRO-1是HCC的潜在血清标志物,并有希望成为HCC患者术后复发转移的预测指标.     

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.     

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.     

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.