Blastocyst MHC 基因转染延长小鼠移植心脏存活时间

目的 探讨Blastocyst MHC基因经供心冠状动脉转染对移植心脏存活时间的影响. 方法 分别以近交系健康雄性Balb/c小鼠和C57BL/6小鼠为供、受者,制备小鼠颈部心脏移植模型,对照组供心以0～4℃托马斯Ⅱ溶液灌注;环孢素A(CsA)组供心用前述方法灌注,术后受者腹腔注射CsA 5 mg·g1·d-1;转染组供心以含Blastocyst MHC基因转染质粒的托马斯Ⅱ溶液灌注;联合处理组供心以含Blastocyst MHC基因转染质粒的托马斯Ⅱ溶液灌注,术后腹腔内注射CsA.观察各组移植心脏存活时间和组织学变化,测定移植心脏组织中Blastocyst MHC基因mRNA表达以及外周血CD4+ CD25+调节性T淋巴细胞(Treg细胞)及CD3+ CD8+ T淋巴细胞的变化. 结果 CsA组、转染组和联合处理组移植心脏存活时间较对照组明显延长(P＜0.115),其中以联合处理组最为显著,达(20.50±5.61)d.转染组术后1、3 d的Blastocyst MHC基因mRNA表达水平较对照组明显升高(P＜0.05).术后7 d,联合处理组的排斥反应程度最轻,其冠状动脉内膜增生也最轻.术后7 d,CsA组和联合处理组Treg细胞明显多于对照组(P＜0.05),而CD3+ CD8+ T淋巴细胞明显少于对照组(P＜0.05). 结论 移植前转染Blastocyst MHC基因能够通过上调Treg细胞、抑制CD3+ CD8+ T淋巴细胞而延长小鼠移植心脏存活时间,与CsA联合有协同作用.     

白介素10在心脏移植排斥反应中的表达及机制

目的　研究白介素10(IL-10)在大白鼠心脏移植排斥反应中心脏局部的表达变化情况，并探讨其参与排斥反应的可能机制。方法　实验动物分5组，A组(对照组)、B组(供体特异性全血输注组)、C组(Anti-IL-2Mab组)、D组(Anti-IL-4Mab组)、E组(Anti-IL-2Mab+环孢霉素A组)，处理受体。将大鼠移植心移植到受体的颈部，观察移植心存活时间、动态病理变化。并于移植术后第1、3、5、7、9、11、14d分别取移植心置于液氮中待测。应用半定量的RT-PCR法动态检测移植心IL-10的表达情况。结果　各组移植心存活时间分别为(8.3±1.7)d、(29.2±7.1)d、(26.4±5.7)d、(10.2±1.9)d、(55.0±10.6)d。其中B组、C组与A组比较差异有显著意义，E组与A组及C组比较分别有极显著意义和显著意义。IL-10在B组、C组及E组均有较强的表达，在A组及D组表达微弱，并与移植物的存活时间密切相关。结论　IL-10参与调节移植排斥反应，其机制可能为Th类细胞因子的免疫偏离。应用Th1类细胞因子单克隆抗体并联用免疫抑制剂可以有效的抑制移植排斥反应，从而延长移植物的存活期。     

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.     

供心体外转染腺病毒介导的CD40Ig融合基因延长小鼠移植心脏存活时间

目的探讨体外转染CD40Ig融合基因对小鼠移植心脏存活时间的影响。方法构建携带小鼠CD40胞外段和人IgGFc融合基因的重组腺病毒载体(AdCD40Ig),以BALB/c小鼠为供者,C57BL/6小鼠为受者,建立小鼠腹部异位心脏移植模型,实验组供心移植前在体外以AdCD40Ig灌注,转染CD40Ig基因,另设空载体转染对照组、非转染对照组和近交系对照组(供、受者均为近交系C57BL/6小鼠)。术后观察移植心的存活及移植物中炎症细胞浸润情况,采用酶联免疫吸附试验(ELISA)检测受者体内CD40Ig融合蛋白表达情况,流式细胞仪检测受者体内产生γ干扰素(IFN-γ)的脾细胞。结果实验组移植心的存活时间达(15.8±0.7)d,明显长于空载体转染对照组和非转染对照组(P<0.01)。术后第2d,实验组受者体内CD40Ig融合蛋白表达最高,1周后明显降低。术后第7d,实验组移植心组织中浸润的炎症细胞明显比未处理对照组和空载体对照组少。实验组产生IFN-γ的CD4+和CD8+T淋巴细胞分别为(2.18±0.16)%和(10.82±0.74)%,与近交系对照组接近,明显低于未处理对照组和空载体对照组(P<0.01)。结论供心体外转染CD40Ig融合基因可有效抑制移植后受者体内同种T淋巴细胞的增殖,并延长移植心的存活时间。     

联合免疫治疗对肝移植大鼠移植肝组织学和外周血Th1/Th2细胞因子的影响

目的用抗CD-40L单抗加小剂量CsA联合免疫治疗肝移植大鼠受体,观察其生存时间?移植肝组织学和Th1/Th2细胞因子谱的变化。方法建立大鼠肝移植模型后,将动物随机分为4组。A组为同基因移植组,SD→SD;B组为同种异体移植组,SD→Wistar,不用任何免疫抑制治疗措施;C组,SD→Wistar,采用CsA处理;D组,SD→Wistar,采用CsA加抗CD-40L(CD-154)单抗处理。观察各组肝移植受体生存期和移植肝病理变化;用ELISA法检测外周血细胞因子水平。结果A,D组均可长期存活,B,C组生存时间分别为(13.8±2.4)d,(29.8±4.1)d;B,C组病理组织切片见中/重度急性排斥反应,D组移植肝组织损伤程度显著减轻,A组基本无排斥反应。B组血清IL-2和IFN-γ高于其余各组(P<0.05),C,D组IL-4,IL-10水平较B组有所升高(但P>0.05),尤其D组IL-10表达水平显著高于B组(P<0.05)。结论联合免疫治疗可有效抑制其急性排斥反应,延长大鼠肝移植受体的生存时间。Th2类细胞因子IL-4和IL-10的高水平表达与诱导移植耐受、抑制排斥反应有重要关系,它有助于大鼠肝移植受体和移植肝的长期存活。     

阻断共刺激信号抑制小鼠小肠移植排斥反应机制的研究

目的证实细胞毒T淋巴细胞相关抗原4免疫球蛋白（CTLA4-Ig）能抑制小鼠小肠移植排斥反应，并研究其作用机理。方法采用显微外科技术建立小鼠异位小肠移植模型，实验分为3组。A组：为同系移植组（供、受者均为BALB／c小鼠）；B组：为同种移植未治疗组（供者为C57BL／6小鼠，受者为BALB／c小鼠），移植后未给予任何治疗；C组：为同种移植共刺激信号阻断组（供者为C57BL／6小鼠，受者为BALB／c小鼠），移植后第2d开始腹腔注射CTLA4-Ig 1mg·kg^-1·d^-1，连用3d。术后观察各组受者的存活时间；移植第6d处死部分受者获取移植物标本，进行组织病理学检查；半定量逆转录聚合酶链反应检测白细胞介素2（IL2）、白细胞介素10（IL-10）、7干扰素（IFN-7）、吲哚胺2，3-双加氧酶（IDO）的mRNA水平；蛋白质印迹法检测移植物中IDO蛋白表达水平。结果A组和C组的中位存活时间均为30d，B组的中位存活时间为6d。A、C组与B组比较，差异有统计学意义（P〈0．01）。病理结果显示，B组排斥反应明显，C组呈轻度排斥反应。IL-2、IFN-γ的mRNA表达水平在A组、C组均较低，而B组则显著增加；IL-10的mRNA转录水平在A、B组较低，C组明显增高。IDO分子mRNA和蛋白的表达检测显示，A、B组的1130分子mRNA和蛋白表达低，c组增高显著。结论应用CTLA4-Ig能抑制小鼠小肠移植排斥反应。IL-2、IFN-γ分子mRNA的高水平表达和排斥反应的程度呈正相关，IL-10分子mRNA表达与排斥反应强度呈负相关。CTLA4-Ig阻断共刺激信号导致T细胞的无能与IDO表达明显相关，说明了IDO所致的“色氨酸饥饿”可能是共刺激信号被阻断后导致活化T细胞无能的机制之一。     

白细胞介素10基因转染对心脏移植排斥反应中细胞黏附分子表达的影响

目的探讨白细胞介素10(IL-10)基因转染对小鼠心脏移植排斥反应中细胞黏附分子CD44、选择素E、淋巴细胞功能相关抗原-1(LFA-1)、血管细胞黏附分子-1(VCAM-1)表达的影响。方法采用小鼠颈部心脏移植模型,将96只小鼠用随机数字表法分为3组,对照组:供、受者各16只,均为C57小鼠;移植组:供、受者各16只,分别为BALB/C、C57小鼠;IL-10组:供、受者各16只,分别为BALB/C、C57小鼠,用IL-10重组腺病毒载体先转染供心。3组均行颈部心脏移植。于术后第5 d取移植心脏,用逆转录聚合酶链反应(RT-PCR)法观察CD44、选择素E、LFA-1、VCAM-1及IL-10 mR-NA的表达情况。结果PCR产物电泳及条带密度扫描显示,移植组CD44、选择素E、LFA-1、VCAM-1与对照组比较表达明显增强(P<0.01);IL-10组与移植组比较表达明显降低(P<0.01)。结论IL-10基因转染对心脏移植排斥反应的免疫抑制作用可能与其抑制CD44、选择素E、LFA-1、VCAM-1等细胞黏附分子的表达有关。     

Th1/Th2类细胞因子转换对小鼠心脏移植物存活的影响

目的 探讨Th1/Th2类细胞因子转换对小鼠心脏移植物存活时间的影响。方法 采用小鼠腹部心脏移植模型，分为同种异体移植组（A组）、同种异体移植+免疫抑制处理组（B组）和同系移植组（C组），每组20对。观察移植物存活时间、供心病理改变、受鼠脾和供心内IFN-γ，IL-2，IL-4及IL-10 mRNA的表达水平。结果 A组及B组移植物平均存活时间分别为（7.8±0.77）d和（14.80±1.01）d，C组移植物存活均超过28d；3组间差异均有显著性（P<0.05）。A组与B组、C组比较，移植物的心肌细胞变性坏死严重，并有大量炎性细胞浸润。A组受鼠脾脏及供心内IFN-γ和IL-10 mRNA表达比其余两组明显增强；3组移植心组织IL-2及IL-4 mRNA均无表达；A组脾脏IL-2 mRNA表达最强；B组脾脏IL-4 mRNA表达明显强于其余两组。结论 Th1/Th2转换在延长移植物存活过程中起重要作用；IL-10也参与移植物排斥反应过程。     

抑制趋化因子受体CCR5减轻小鼠同种异体移植心脏急性排斥反应的研究

目的 研究抑制趋化因子受体CCR5减轻小鼠同种异体移植心脏急性排斥反应的作用机制.方法 采用小鼠颈部心脏移植模型,将96只小鼠用随机数字表法分为4组,每组24只,供、受者各12只,A组术后给予anti-CCR5 mAb和CsA,B组术后给予anti-CCR5 mAb,C组术后给予CsA,D组为对照组,术后给予生理盐水.于术后第7d取各组移植心组织6例,检测CCR5及IL-2和IL-10的表达差异,其余6例用于观察移植心脏存活时间.结果 A、B、C组小鼠移植心脏存活时间明显延长,其CCR5及IL-2的表达较D组明显减少,IL-10的表达明显增加.结论 抑制趋化因子受体CCR5对同种异体移植心脏有明显的保护作用,可能与细胞因子的表达有关.     

输注转染MyD88siRNA基因的供者树突状细胞延长小鼠移植心存活时间

目的 探讨输注供者来源的转染了髓样分化因子88(MyD88)siRNA基因的树突状细胞(DC)在延长同种小鼠移植心存活时间中的作用及机制.方法 以脂质体为载体,将化学合成的MyD88siRNA导入BALB/c小鼠(供者)骨髓来源的DC中,制备转染MyD88siRNA基因的DC(MyD88siRNA-DC).随机将27只C57BL/6小鼠(受者)平均分为磷酸盐缓冲液(PBS)对照组、培养8 d的DC(Day8-DC)组及MyD88siRNA-DC组,分别将PBS、Day8-DC及MyD88siRNA-DC输注至受者体内.于输注后第7、14和21天时应用免疫双荧光染色法观察供者DC在受者脾脏内的存活情况;混合淋巴细胞反应(MLR)测定受者脾脏内T淋巴细胞对供者同种抗原的反应性.另取27对供、受者(BALB/c小鼠和C57BL/6小鼠),通过袖套管技术建立颈部异位心脏移植模型,随机平均分为PBS对照移植组、Day8-DC移植组及MyD88siRNA-DC移植组,各组于移植前7 d分别经受者门静脉注射0.5 ml PBS、2.0× 106个Day8-DC及2.0× 106个MyD88siRNA-DC.于输注后第7天,观察各组移植心的存活时间;病理检查观察排斥反应程度;酶联免疫吸附试验测定受者血清巾Th1及Th2型细胞因子[γ干扰素(INF-γ)、白细胞介素(IL)-12、IL-4和IL-10]水平的变化.结果 MyD88siRNA-DC在受者脾脏内的存活时间明显延长,MyD88siRNA-DC组受者脾脏内T淋巴细胞对供者抗原的反应性最低(P＜0.01).PBS对照移植组、Day8-DC移植组及MyD88siRNA-DC移植组移植心的存活时间分别为:(6.67±1.37)d、(13.67±2.25)d和(24.50±4.42)d,与PBS对照移植组相比,Day8-DC移植组移植心存活时间延长(P＜0.01),而MyD88siRNA-DC移植组移植心存活时间较Dby8-DC移植组进一步延长(P＜0.01);MyD88siRNA-DC移植组移植心排斥反应病理分级最低,受者血清中INF-γ和IL-12水平显著降低(P＜0.01),而IL-4和IL-10水平明显升高(P＜0.01).结论 输注转染MyD88siRNA基因的供者DC能够延长同种小鼠移植心的存活时间;其机制可能与诱导受者Th1/Th2免疫偏移及形成供、受者微嵌合状态有关.     

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.     

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.