益生注射液延缓大鼠慢性移植肾肾病的进程

目的　探讨中药益生注射液对大鼠慢性移植肾肾病(CAN)的防治效果。方法　分别采用封闭群雄性SD大鼠和Wistar大鼠作为供、受者进行原位肾移植,术中强化缺血再灌注损伤,建立CAN加快动物模型。将成模大鼠随机分为4个组,A组术后仅给予环孢素A(CsA)10 mg·kg-1·d-1治疗10 d;B、C组除接受CsA治疗外,还分别给予益生注射液4 mg/kg、8 mg/kg;D组除接受CsA治疗外,还给予霉酚酸酯(MMF)10 mg/kg。观察各组术后4、8及12周时的血肌酐水平、移植肾形态学变化及移植肾组织中转化生长因子β1(TGF β1)的表达。结果　术后4周起,A组的血肌酐水平明显高于其它三组(P<0.05);C组第12周时的血肌酐水平高于D组(P<0.05)。除A组术后12周出现TGF β1 表达下调外,各组术后TGF β1 的表达均呈上升趋势,A组4周和8 周时的表达最强;C组和D组的TGF β1 表达较弱。术后8周A组出现明显的CAN病理改变,而C组和D组出现明显血管内膜增生的时间明显晚于A组,且程度较轻。结论　中药益生注射液具有与霉酚酸酯类似的能够延缓慢性移植肾肾病进程的作用。     

免疫抑制剂对大鼠慢性移植肾肾病中转化生长因子β1/Smads通路的影响及意义

目的 探讨不同免疫抑制剂对慢性移植肾肾病(CAN)中转化生长因子β1(TGF-β1)/Smads通路的影响及意义.方法 采用SD大鼠到Wistar大鼠的强化CAN模型,然后将模型大鼠随机分为对照组(不行处理)、环孢素A组(给予环孢素A 6 mg·kg-1·d-1)、他克莫司组(给予他克莫司0.15 mg·kg-1·d-1)、霉酚酸酯组(给予霉酚酸酯20 mg·kg-1·d-1)和西罗莫司组(给予西罗莫司0.8mg·kg-1·d-1).分别于术后4、8、12周处死动物,观察移植肾组织的病理变化,用免疫组织化学法和时荧光定量聚合酶链反应测定肾组织中TGF-β1、Smad2和Smad7蛋白及其基因的表达.结果 术后各组均呈现CAN的病理改变,环孢素A组和他克莫司组的病变程度较对照组重,而霉酚酸酯组和西罗莫司组的病变轻于对照组.术后各时间段,环孢素A组和他克莫司组TGF-β1和Smad2蛋白及其Mrna的表达明显高于对照组(P＜0.05),而Smad7蛋白及其Mrna的表达明显低于对照组(P＜0.05);霉酚酸酯组和西罗莫司组TGF-β1和Smad2蛋白及其Mrna的表达明显低于对照组(P＜0.05),而Smad7蛋白及其Mrna的表达明显高于对照组(P＜0.05).结论 发生CAN时,环孢素A和他克莫司可上调TGF-β1的表达,影响TGF-β1/Smads通路,加重其病理损害,而霉酚酸酯和西罗莫司的作用与之相反.     

不同免疫治疗方案诱导大鼠原位肝移植免疫耐受的实验研究

目的 观察抗CD-40L单抗加小剂量CsA联合免疫治疗对肝移植大鼠受体免疫耐受诱导的作用.方法 在建立稳定大鼠肝移植模型的基础上,将肝移植模型分为5组.A组为SD→SD对照组;B组为SD→Wistar对照组,A,B组术后不用任何治疗措施;C组为SD→Wistar,术后用CsA1～5 d;D组为SD→Wistar,术后用CsA 1～5 d加抗CD-40L(CD-154)单抗0～2d;E组为D组+术前供体特异性输血(DSBT).观察受体存活时间、移植肝病理改变以及术后外周血中细胞因子的变化.结果 A,D,E组受体大鼠存活时点(均>60 d)均明显长于B组和C组.D,E组移植肝急性排斥反应明显减轻.B组IL-2和IFN-γ的血清水平显著高于其余各组(P＜0.05).B,C,D,E 4组IL-4和IL-10较A组均有明显增加,尤其D,E组的IL-10表达较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,可有效延长肝移植大鼠受体生存时间、减轻急性排斥反应并诱导Th2类细胞因子的高水平表达,有助于受体和移植肝的长期存活.     

TGF-β1修饰的未成熟树突状细胞对大鼠移植小肠细胞凋亡的影响

目的 探讨经TGF-β1修饰的未成熟树突状细胞(imDC)预处理大鼠小肠移植受体后移植肠细胞凋亡的变化及意义.方法 选用近交系F344/N和BN大鼠建立全小肠异位移植模型,分4组,每组24只.A组:同基因移植组(BN→BN);B组:异基因移植组(F344/N→BN);C组:F344/N→BN异基因移植+TGF-β1基因转染imDC;D组:F344/N→BN异基因移植+TGF-β1基因转染imDC+FK506.术后3、5、7 d各处死6只,取出移植肠.行免疫组化检测Bcl-2和Bax表达,TUNEL及电镜观察细胞凋亡.同期进行移植肠组织病理学检查.结果 C组中Bcl-2在术后有轻度下降,而Bax的表达则略有升高,但明显低于B组,差异有统计学意义(P＜0.05);D组术后Bcl-2及Bax的表达与A组无明显差异.C组的凋亡细胞数在术后逐渐增加,但数量始终较少,与B组比较差异有统计学意义(P＜0.05);D组仅见少量凋亡细胞.结论 经TGF-β1基因转染的imDC预处理受体可以抑制细胞凋亡,从而减轻小肠移植术后急性排斥反应的程度.     

丹参抑制转化生长因子-β1诱导的肌源性干细胞向肌成纤维母细胞分化

目的 观察丹参对失神经骨骼肌肌源性干细胞(MDSCs)向肌成纤维母细胞分化的抑制作用.方法 采用差速贴壁法分离出大鼠失神经骨骼肌MDSCs,加入转化生长因子-β1(TGF-β1)和丹参进行干预,将细胞分为3组:A:对照组;B:10 μg/L TGF-β1组;C:10 μg/L TGF-β1+ 150 mg/L丹参组.荧光实时定量聚合酶链反应(qRT-PCR)和Western blot检测各组细胞在干预后5个时间点α-平滑肌肌动蛋白(α-SMA)和波形蛋白(Vimentin) mRNA和蛋白表达.结果 与A组比较,B组和C组细胞α-SMA、Vimentin的mRNA在干预后第2、3、5、7天均明显升高(P＜0.05),其蛋白表达在干预后第3、4、6、8天亦显著升高(P＜0.05);与B组比较,C组细胞α-SMA、Vimentin的mRNA和蛋白在对应时间点均明显降低(P＜0.05).结论 丹参能抑制TGF-β1诱导的失神经骨骼肌MDSCs向肌成纤维母细胞的分化.     

大鼠肾移植后抗波形蛋白抗体升高与慢性移植肾肾病的相关性

目的 研究大鼠肾移植术后抗波形蛋白抗体的表达水平与慢性移植肾肾病(CAN)的相关性.以及不同免疫抑制剂对其的影响.方法 选取近交系F344大鼠作为同系肾移植的供、受者(共9对),选取F344和Lewis大鼠分别作为同种肾移植的供、受者(共27对).同系移植组受者术后不给予免疫抑制剂;同种移植组受者术后10 d内给予环孢素A(CsA),然后将同种移植组受者随机平均分为生理盐水(NS)组、CsA组和霉酚酸酯(MMF)组(每组9只),分别给予NS、CsA和MMF灌胃.术后第4、8和12周时分别处死每组受者3只,观察CAN的进展、波形蛋白及其基因的表达以及抗波形蛋白抗体的水平,取正常大鼠(包括F344和Lewis大鼠)作为对照.结果 观察期内同系移植组未发生CAN;而同种移植组发生了CAN,且不断加重,其中CsA组和NS组的CAN病理改变非常明显,而MMF组明显较轻.术前所有受者血清中均未检测到抗波形蛋白IgM和IgG抗体,术后也未检测到抗波形蛋白IgM抗体;术后同系移植组仅检测到微量的抗波形蛋白IgG抗体,同种移植组检测到大量的抗波形蛋白IgG抗体.随着CAN的进展,同种移植中,CsA组和NS组血清抗波形蛋白IgG抗体的水平逐渐增高,而MMF组抗体水平的增高显著低于NS组(P<0.05),但仍显著高于同系移植组(P<0.05).结论 大鼠同种肾移植术后,受者体内可产生抗波形蛋白IgG抗体,且产生的时间早于CAN,抗波形蛋白IgG抗体水平也会随着CAN的进展而增高.MMF可抑制抗波形蛋白IgG抗体的产生,CsA无此作用.     

缬沙坦对糖尿病大鼠肾皮质TGF-β1表达的影响

目的:探讨血管紧张素Ⅱ受体拮抗剂缬沙坦(Valsartan)对实验性糖尿病大鼠肾皮质TGF-β1表达的影响,为糖尿病肾病的防治提供实验性理论基础.方法:选择健康雄性SD大鼠24只,任取其中16只腹腔注射链脲佐菌素制成糖尿病大鼠模型.将糖尿病大鼠随机分为糖尿病缬沙坦治疗组(A组,8只,缬沙坦10 mg*kg-1*d-1灌胃);糖尿病对照组(B组,8只);其余8只为正常对照组(C组).分别于实验第6周末测定各组大鼠血糖、血肌酐、尿白蛋白排泄率,对肾脏标本进行光镜观察,用图像分析仪测量各组大鼠平均肾小球面积、平均肾小球体积.并取各组大鼠肾皮质提取RNA,用逆转录-PCR(RT-PCR)方法对肾皮质TGF-β1 mRNA表达进行半定量分析.结果:在糖尿病第6周末,B组上述指标较C组均有不同程度的升高(P＜0.01),而A组则显著低于同时期的B组.其中,A组、C组尿白蛋白排泄率始终无统计学差异,肾小球平均面积、平均体积A组显著低于B组(P＜0.01).RT-PCR半定量结果分析显示,B组TGF-β1 mRNA表达较A组、C组显著增高(P＜0.01),A组TGF-β1 mRNA表达较C组为高(P＜0.01),但仍较B组为低(P＜0.05).结论:缬沙坦能够抑制肾组织TGF-β1 mRNA的表达,减少糖尿病大鼠的尿白蛋白,减轻及延缓肾小球硬化,发挥保护肾脏的作用.     

缬沙坦对糖尿病大鼠肾皮质TGF—βl表达的影响

目的探讨血管紧张素Ⅱ受体拮抗剂缬沙坦(Valsartan)对实验性糖尿病大鼠肾皮质TGF-β1表达的影响,为糖尿病肾病的防治提供实验性理论基础.方法选择健康雄性SD大鼠24只,任取其中16只腹腔注射链脲佐菌素制成糖尿病大鼠模型.将糖尿病大鼠随机分为糖尿病缬沙坦治疗组(A组,8只,缬沙坦10 mg*kg-1*d-1灌胃);糖尿病对照组(B组,8只);其余8只为正常对照组(C组).分别于实验第6周末测定各组大鼠血糖、血肌酐、尿白蛋白排泄率,对肾脏标本进行光镜观察,用图像分析仪测量各组大鼠平均肾小球面积、平均肾小球体积.并取各组大鼠肾皮质提取RNA,用逆转录-PCR(RT-PCR)方法对肾皮质TGF-β1 mRNA表达进行半定量分析.结果在糖尿病第6周末,B组上述指标较C组均有不同程度的升高(P＜0.01),而A组则显著低于同时期的B组.其中,A组、C组尿白蛋白排泄率始终无统计学差异,肾小球平均面积、平均体积A组显著低于B组(P＜0.01).RT-PCR半定量结果分析显示,B组TGF-β1 mRNA表达较A组、C组显著增高(P＜0.01),A组TGF-β1 mRNA表达较C组为高(P＜0.01),但仍较B组为低(P＜0.05).结论缬沙坦能够抑制肾组织TGF-β1 mRNA的表达,减少糖尿病大鼠的尿白蛋白,减轻及延缓肾小球硬化,发挥保护肾脏的作用.     

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。     

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.