胰腺腺泡细胞凋亡和Fas/Fas配体表达在大鼠胰腺移植急性排斥反应中的作用

目的探讨大鼠胰腺移植后细胞凋亡的变化、Fas/Fas配体(FasL)的表达及其与急性排斥反应的关系。方法实验分为同基因移植组和异基因移植组。分别于术后第3、5、7天处死受体,取移植胰腺,应用原位末端标记法(TUNEL)检测细胞凋亡,计算凋亡指数(AI),应用免疫组织化学及Westernblot检测Fas/FasL的表达。结果细胞凋亡主要发生在胰腺腺泡细胞,同基因移植组有散在的腺泡细胞凋亡,AI在术后无明显变化,Fas/FasL表达阴性;异基因移植组在术后第3、5、7天胰腺腺泡细胞凋亡发生率逐渐增加(28.40±3.75,39.40±5.59,57.30±8.53,P<0.01),Fas/FasL表达逐渐增强,AI与急性排斥反应程度呈显著正相关(rs=0.932,P<0.01)。结论胰腺腺泡细胞凋亡和Fas/FasL表达在胰腺移植急性排斥反应中发挥重要作用,凋亡指数对胰腺移植急性排斥反应的诊断有一定的参考价值。     

自身免疫性肝炎和原发性胆汁性肝硬化患者肝组织和外周血单个核细胞Fas及FasL的检测

目的 观察自身免疫性肝炎(AIH)和原发性胆汁性肝硬化(PBC)患者肝组织和外周血单个核细胞(PBMC)Fas、FasL的表达,探讨细胞凋亡在自身免疫性肝病(AILD)发病机制中的作用.方法 采用免疫组织化学技术对10例AIH、20例PBC患者肝组织和PBMC中Fas、FasL进行检测,正常对照为10例健康献血者.结果 AIH 患者PBMC中Fas、FasL检出率分别为100%和90%, Fas、FasL平均阳性细胞率分别为78%和65%;PBC患者PBMC中Fas、FasL检出率均为90%,平均阳性细胞率分别为62%和59%.在肝组织中Fas、FasL表达于肝细胞和淋巴细胞:9例AIH Fas阳性颗粒见于肝细胞浆,其中1例胞膜、胞浆同时阳性;8例FasL阳性颗粒表达于肝细胞浆;Fas、FasL阳性肝细胞多聚集于汇管区周围.同时在汇管区周围浸润的淋巴细胞中也可见Fas或FasL的阳性表达.17例PBC患者Fas阳性颗粒表达于肝细胞浆,其中4例胞膜、胞浆同时阳性;16例PBC FasL阳性,见于肝细胞浆,在肝组织中浸润的淋巴细胞浆中Fas、FasL均有表达.AIH和PBC患者Fas、FasL表达显著高于正常对照.结论 AIH和PBC患者的Fas、FasL表达增加,细胞凋亡可能在AIH和PBC的发病机制中起重要作用.     

小鼠单侧睾丸损伤后环孢素A对Fas系统的影响

目的 :研究昆明小鼠 (KM小鼠 )单侧注射冰乙酸致睾丸损伤后环孢素A(CsA)对对侧睾丸生精功能和Fas系统表达的影响。　方法 :6 0只KM小鼠随机分为 4组 :A组为对照组 ,B组为单侧睾丸损伤组 ,C组为单侧睾丸损伤后 6h切除损伤睾丸组 ,D组为单侧睾丸损伤后 6h内开始腹腔注射CsA组。 4周后取对侧附睾尾 ,计数精子及其活率 ,对侧睾丸作石蜡切片苏木精 伊红染色和免疫组化链霉素抗生物素蛋白过氧化物酶连结 (SP)法检测Fas和FasL的表达。　结果 :D组附睾尾精子和活率计数显著高于B组 (P <0 .0 5 ) ,D组的FasL和Fas较B组显著降低 (2 4 .3± 7.0vs37.8± 5 .8和 17.8± 4 .3vs32 .4± 3.6 ,P <0 .0 5 )。　结论 :KM小鼠单侧睾丸损伤后CsA可以通过抑制Fas和FasL的表达 ,降低生精细胞凋亡 ,维持生精功能的稳定     

门静脉高压症病人肝内血管内皮细胞凋亡的研究

目的　研究门静脉高压症病人肝组织内血管及肝窦壁内皮细胞的凋亡及其对肝微循环的影响。方法　对 37例门静脉高压症病人、10例正常人肝组织 ,用TUNEL法检测血管内皮细胞及肝窦壁内皮细胞凋亡 ,免疫组化法检测Bax和Bcl 2基因的蛋白表达。结果　肝硬化门静脉高压症病人 ,门管区血管内膜破坏、断裂 ,内皮细胞脱落。管腔内血栓形成。血管壁和肝窦壁内皮细胞TUNEL 阳性细胞数为 (2 9 2 9± 4 15 ) % ,与对照组仅 (0 5± 0 2 ) % ,有显著性差异 (P <0 0 0 1) ;门管区血管内皮细胞和肝窦壁内皮细胞Bax和Bcl 2强阳性表达率分别为 (33 5 1± 5 6 9) %和 (2 4 6 4± 5 87) % ,对照组均为阴性 (P <0 0 0 1)。结论　肝硬化门静脉高压症病人门管区内皮细胞和肝窦壁内皮细胞凋亡和坏死明显增加 ,内皮细胞的凋亡和坏死激活凝血系统 ,促使血栓形成 ,从而破坏了肝脏微循环。     

肝海绵状血管瘤内皮细胞凋亡与增殖活性的研究

目的　探讨肝海绵状血管瘤 (CHL)的发生、发展与内皮细胞凋亡及增殖的关系。方法　以 2 2例肝海绵状血管瘤石蜡标本为研究对象 ,以草莓状血管瘤和正常肝脏汇管区小血管为对照 ,采用免疫组化ABC法检测增殖细胞核抗原 (PCNA )的表达 ,采用TdT介导的脱氧核苷酸原位末端标记法(TUNEL法 )检测细胞凋亡。结果　CHL组内皮细胞增殖指数 (13 .2 7± 5 .79)与正常肝脏汇管区小血管组 (10 .85± 4.79)差异无显著性 (t =1.15 ,P >0 .0 5 ) ,而显著低于草莓状血管瘤组 (2 9.3 1± 8.5 5 ,t =6.2 4,P <0 .0 1)。CHL组内皮细胞凋亡指数 (3 .49± 1.3 6)与正常肝脏汇管区小血管组 (2 .65± 1.0 6)差异无显著性 (t =1.72 ,P >0 .0 5 ) ,显著低于草莓状血管瘤组 (11.3 8± 2 .66,t=11.18,P <0 .0 1)。结论　CHL的发生、发展与内皮细胞的增殖及凋亡无关 ,此亦可能是CHL未见癌变的生物学基础。     

凋亡相关蛋白及粘附分子在大鼠心脏急性排斥反应中的作用

目的 探讨凋亡及凋亡相关因子Fas／FasL、Bcl-2/Bax，粘附分子ICAM-1、P-selectin、E-selectin、L-Selectin、PECAM-1和VCAM-1在心脏移植中的表达及意义。方法 用免疫组织化学方法和原位杂交法，检测大鼠心脏移植后不同时间(1、3、5、7d)、Fas／FasL、ICAM-1、P-selectin、L-selectin、E-selectin蛋白、Bcl-2/Bax、VCAM-1、PECAM-1 mRNA的表达情况。结果 随着移植后天数的增加，细胞凋亡增多，Fas／FasL、Bax表达增加，粘附分子ICAM-1、VCAM-1、PECAM-1表达也增加，Selectin表达较少。正常大鼠肝脏未见细胞凋亡及粘附分子的表达。结论 细胞凋亡和粘附分子ICAM-1、VCAM-1、PECAM-1表达增加可能与心脏移植后急性排斥反应有关，而Fas／FasL、Bax可能促进了凋亡的发生。     

5-Fu诱导HepG2细胞凋亡过程中Fas抗原和bcl-XL蛋白的表达及意义

目的　研究 5 -氟尿嘧啶 (5 -Fu)诱导人肝癌HepG2细胞凋亡过程中Fas抗原和bcl-XL 蛋白的表达及意义。方法　采用免疫细胞化学法对 5 -Fu处理的HepG2细胞进行染色 ,运用图像处理和分析系统定量分析Fas抗原和bcl-XL 蛋白表达。流式细胞仪检测抗 -Fas -抗体对氟尿嘧啶诱导人肝癌HepG2细胞凋亡百分率的影响。结果　在未用药处理的对照组细胞Fas抗原呈弱表达(0 .17± 0 .0 3) ,加入 0 .0 1mol L 5 -Fu后Fas阳性表达的细胞数目增加 ,表达强度增强。作用 16h后Fas抗原表达强度达高峰 (0 .4 5± 0 .0 5 ) ,与对照组比较两者有显著差异 (P <0 .0 1)。但在 0 .0 1mol L5 -Fu诱导HepG2细胞凋亡过程中癌基因蛋白bcl-XL 表达逐渐减弱 ,经药物处理 4、8、16、2 4h后 ,其表达分别为 0 .2 8± 0 .0 3、0 .2 0± 0 .0 3、0 .14± 0 .0 3和 0 .0 7± 0 .0 2。癌基因蛋白bcl-XL 的表达与Fas抗原表达呈负相关 (r =- 0 .787,P <0 .0 1)。流式细胞仪分析显示 5 -Fu作用 4 8h后 ,肝癌细胞凋亡百分率为 (16 .2 3± 0 .90 ) % ,而加入抗 -Fas -抗体后细胞凋亡百分率显著上升为 (40 .13± 1.4 5 ) % (P<0 .0 1)。结论　 5 -Fu诱导HepG2细胞凋亡是通过Fas依赖途径 ,属于第Ⅱ型Fas信号传导途径。该凋亡过程可能与功能性Fas抗原表达上     

生长激素对急性坏死性胰腺炎大鼠肠粘膜上皮细胞凋亡的影响

目的观察生长激素 (GH)对急性坏死性胰腺炎 (ANP)大鼠早期肠粘膜上皮细胞凋亡的调节作用。方法ANP模型大鼠分ANP组和ANP加GH治疗组 ,假手术组 (SO组 )作为对照。分别用DNA琼脂糖凝胶电泳、流式细胞仪分析和dUTP缺口末端标记法研究肠粘膜细胞凋亡 ,免疫组织化学方法检测肠粘膜凋亡相关蛋白FasL及Bax表达。结果ANP大鼠各时点肠粘膜DNA电泳均可见典型的凋亡“梯形”条带 ,而GH治疗组仅于 3h出现“梯形”条带。术后 3h、6h、12h、2 4h肠粘膜脱落细胞凋亡比例分别为 :SO组为 (5 4± 4) %、(2 8± 6 ) %、(39± 5 ) %、(2 9± 11) % ,ANP组为 (5 0± 11) %、(80± 9) %、(4 8± 17) %、(5 0± 10 ) % ,术后 6h较SO组明显增高 (P <0 0 1) ;GH治疗组 ,(4 8± 11) %、(2 7± 15 ) %、(4 2± 7) %、(30± 10 ) % ,与SO组各时点比较差异无显著意义 ,且术后 6h较ANP组降低(P <0 0 1)。术后 3h、6h、12h、2 4h各时点肠粘膜细胞凋亡指数分别为 :SO组为 (6± 2 )、(8± 2 )、(11±1)、(5± 1) ,ANP组为 (18± 4)、(2 0± 3)、(15± 2 )、(14± 2 ) ,较SO组明显增高 (P <0 0 1) ;GH治疗组为(10± 2 )、(10± 2 )、(13± 2 )、(14± 4) ,其中术后 3h、6h较ANP组降低 (P <0 0 1)。FasL及Bax蛋白在假手术组呈弱表达 ,AN     

Fas/FasL途径在造血干细胞移植免疫中的实验研究

目的　探讨转染FasL的CD34+ 细胞对同种抗原特异性T细胞和白血病细胞凋亡的影响。方法　丝裂霉素C预处理表达外源FasL的骨髓CD34+ 细胞 ,分别与经过富集的T细胞 (刺激细胞 /效应细胞比例为 5∶1)和白血病细胞U937混合培养 ,借助原位末端标记法 (TUNEL)和流式细胞仪 (FCM )检测T细胞和白血病细胞的凋亡率。结果　分别以未转染和转染外源FasL的CD34+ 细胞为刺激细胞 ,5d后 ,T细胞凋亡率分别为 :3.2 %± 1.1%、12 .1%± 1.5 % (P <0 .0 1) ,经IL 2作用后 ,凋亡率上升至 17.6 %± 1.3% (P <0 .0 1) ;与白血病细胞U937混合培养 18h后 ,白血病细胞凋亡率分别为 :5 .0 %± 1.3%、10 .8%± 0 .6 % (P <0 .0 1) ,加入阿糖胞苷后 ,凋亡率上升至 17.9%±1.3% (P <0 .0 1)。结论　转染外源FasL的骨髓CD34+ 细胞 ,可诱导同种抗原特异性T细胞和白血病细胞凋亡。提示通过Fas/FasL途径可选择性清除移植物中同种抗原特异性T细胞 ,有望为造血干细胞移植中防治移植物抗宿主病 (GVHD) ,保留移植物抗白血病效应 (GVL)提供新的策略。     

Fas配体阳性睾丸细胞和环孢素A对移植胰岛细胞存活起协同保护作用

目的　探讨Fas配体 (FasL)阳性睾丸细胞与胰岛细胞共移植后联用环孢素A(CsA)对移植胰岛细胞存活的协同保护作用。　方法　将同种大鼠胰岛细胞与睾丸Sertoli细胞同侧或异侧共移植于 4 1只糖尿病SD大鼠受体肾包膜下。实验大鼠分 7组 ,术后酌用CsA ,观察各组大鼠移植物存活情况。　结果　单纯胰岛细胞移植 (对照组 )后胰岛细胞的平均存活期为 (4 6± 1 1)d ,加用CsA存活期明显延长至 (2 1 8± 4 7)d(P <0 0 1)。与 1× 10 7个睾丸细胞同侧共移植的胰岛细胞平均存活期超过 (5 7 5± 4 0 )d ,但如移植前先封闭睾丸细胞表达的FasL后 ,移植的胰岛细胞平均存活期缩短为(5 8± 2 6 )d。胰岛细胞与 1× 10 5个睾丸细胞分别共移植于两侧肾包膜下 ,术后联用CsA ,胰岛细胞的平均存活期超过 (5 5 0± 6 5 )d ,与 1× 10 7个睾丸细胞同侧共移植的存活期相近 ,但比对照组或CsA组则显著延长 (P <0 0 1)。当胰岛细胞与 1× 10 6个睾丸细胞分别共移植且不用CsA时 ,胰岛细胞存活期平均仅为 (11 5± 3 1)d ,但仍较对照组延长 (P <0 0 5 )。　结论　表达FasL的睾丸细胞与CsA联用后可通过不同机制抑制胰岛细胞移植排斥反应而起到全身的协保护作用。     

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.     

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.     

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.     

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.