NF-κBp50基因缺失对小鼠实验性急性胰腺炎的影响

目的:实验诱导急性胰腺炎,观察p50基因敲除小鼠胰腺组织结构和功能的变化,探讨NF-κB在急性胰腺炎病理过程中的作用。方法:蛙皮素诱导建立野生小鼠和p50基因敲除小鼠的胰腺炎动物模型,检测各组小鼠p50、p65和cRel蛋白的表达情况,NF-κB DNA结合活性,血清淀粉酶和脂肪酶水平,胰腺组织的细胞坏死和凋亡情况和胰蛋白酶活性。结果:p50基因敲除小鼠缺乏p50蛋白表达,但p65和cRel蛋白代偿性增加。同野生型小鼠相比,p50基因敲除小鼠在发生急性胰腺炎时,NF-κB活性降低、细胞凋亡增加、细胞坏死减少,血清淀粉酶、脂肪酶和胰蛋白酶活性下降。结论:p50基因缺失后,NF-κB的其他亚单位蛋白表达代偿性增加;NF-κB对胰腺细胞坏死和凋亡有重要的调节作用,能减轻急性胰腺炎的病情。     

髓系触发受体-1在脆弱类杆菌诱导小鼠脓毒血症中的作用

目的 探讨小鼠TREM-1基因重组慢病毒干扰载体(Lentivector,LV)TREM-1 vshRNA对脆弱杆菌脓毒血症小鼠脾脏中促炎症因子TNF-α,IL-1β,IL-6表达及NF-κB通路的影响.方法 将清洁级BALB/c雄性小鼠分成4组,即正常对照组(C组),脆弱类杆菌脓毒症模型生理盐水组(S组),TREM-1 vshRNA干扰实验组(T组)和GFPvshRNA干扰实验组(G组).观察各组中小鼠脾内TREM-1,TNF-α,IL-1β,IL-6的蛋白表达以及IkBa,pDAP12,NF-κB p65的表达情况的变化.结果 与C组比,T组TREM-1 mRNA及蛋白表达均有显著增加(P＜0.01);T,G,S组脾细胞中TNF-α,IL-1β,IL-6的含量均较C组显著增加(P＜0.01);T组脾细胞中TNF-α,IL-1β,IL-6的含量均较S,G组明显降低(P＜0.01).S组脾细胞中的pDAPl2和核内NF-κB p65蛋白表达水平明显增强,IκBa蛋白表达水平降低;而T组与S组比较,pDAP12和NF-κB p65蛋白的表达水平显著下调.结论 小鼠TREM-1基因重组慢病毒干扰载体可选择性抑制TREM-1表达,下调脆弱类杆菌诱导的促炎症因子的分泌,而转染可能是通过下调DAPl2的表达,稳定IkBa/NF-κB复合物,抑制TNF-α,IL-1β,IL-6,IL-8基因的转录,而对脆弱类杆菌脂多糖炎症反应产生抑制作用.     

拮抗Toll样受体4的表达对内毒素血症小鼠肾脏损伤的保护作用

目的观察拮抗Toll样受体4（TLR4）的表达对内毒素血症小鼠肾脏损伤的保护作用以及对细胞核因子-κB（NF-κB）p65的影响。 方法采用内毒素（LPS）诱导的小鼠急性肾功能衰竭模型,并应用TLR4单克隆抗体进行干预,观察TLR4单克隆抗体对内毒素血症小鼠的肾脏组织学、血清肌酐（Cr）、尿素氮（BUN）、胱抑素C、白细胞介素（IL）-1β、IL-6水平以及肾组织中TLR4及NF-κB水平的影响。 结果与模型组比较,TLR4单克隆抗体能够明显改善内毒素血症小鼠肾脏组织病理学损害;降低血清中Cr、BUN、胱抑素C、IL-β和IL-6水平（t = 7.20、7.86、9.99、8.79、3.92,P均< 0.05）,并且降低肾组织中TLR4及NF-κB p65水平（t = 20.94、11.21,P均< 0.05）。 结论TLR4单克隆抗体能够保护内毒素血症小鼠肾脏组织损伤,其作用机制可能与调节TLR4/NF-κB信号转导通路有关。     

核因子-κB反义寡核苷酸对肝纤维化小鼠肝组织核因子-κB活性和病理改变的影响

目的 应用核因子(NF)-κB反义寡核苷酸(ASON)治疗肝纤维化小鼠模型,观察NF-κB p65 ASON对小鼠肝组织NF-κB活性和肝纤维化程度的影响,探讨NF-κB p65 ASON治疗肝纤维化的可能机制.方法 实验小鼠分组:正常组(8只)、肝纤维化模型组(8只)、反义寡核苷酸(NF-κB p65 ASON)治疗组(8只)、正义寡核苷酸(SON)治疗组(8只)、错义寡核苷酸(MSON)治疗组(8只)、NF-κBp65 ASON对照组(8只)、SON对照组(8只)和MSON对照组(8只);采用凝胶迁移率变动分析(EMSA)检测NF-κB DNA结合活性;病理切片(Masson染色)评价肝纤维化小鼠模型肝纤维化程度.结果 NF-κB p65 ASON治疗组小鼠肝组织NF-KB活性(12411.75±502.78)、肝纤维化病理积分(1.13±0.64)比模型组(16 346.88 ±449.05、2.88±0.64)明显降低,差异有统计学意义(P<0.01).soN治疗组(16460.38±575.26、2.75±1.17)和MSON治疗组(15 959.25±746.27、3.00±0.53)的NF-κB活性、肝纤维化病理积分与模型组比较差异无统计学意义(P>0.01).结论 NF-κB p65 ASON能显著抑制小鼠肝组织的NF-κB活性,降低肝纤维化程度.     

急性坏死性胰腺炎胰腺腺泡细胞活性与血液炎症细胞因子变化关系的研究

目的探讨急性坏死性胰腺炎(ANP)胰腺腺泡细胞核转录因子NF-κB与血液中炎症细胞因子之间的变化关系。方法采用5％牛磺胆酸钠胰管逆行注射制备ANP动物模型。SD雄性大鼠40只,随机分为ANP模型组和空白对照组。采用电泳迁移率移动分析法检测胰腺腺泡细胞胞核NF-κB活性、Western-blot法检测胰腺腺泡细胞胞质IκBa活性及ELISA法检测血液IL-2、IL-6、 IL-10、TNF-α及ICAM-1含量。结果 ANP模型组胰腺腺泡细胞胞核NF-κB活性在1h、3h、5h及 7h均较空白对照组显著升高[(31．4±5．7)μmol／L比(8．3±2．4)μmol／L、(39．4±6．4)μmol／L比 (10．7±2．6)μmol／L、(33．8±6．0)μmol／L比(11．5±2．7)μmol／L、(25．7±4．9)μmol／L比(9．4± 2．6)μmol／L](P<0．01);胰腺腺泡细胞胞质IκBa活性在1 h、3 h、5 h及7 h均较空白对照组显著降低[(6．4±1．2)μmol／L比(11．4±1．8)μmol／L、(5．9±1．6)μmoL／L比(12．5±2．2)μmol／L、 (6．8±1．4)μmol／L比(11．7±1．9)μmol／L、(7．0±0．9)μmol／L比(10．8±1．7)μmol／L](P< 0．01);血液中IL-2、IL-6、IL-10、TNF-α及ICAM-1在1 h、3 h、5 h及7 h亦较空白对照组显著升高(P< 0．05),且NF-κB活性变化与血液中IL-2、IL-6、IL-10、TNF-α及ICAM-1含量变化呈正相关。结论 ANP胰腺腺泡细胞NF-κB活性显著升高,可导致大量炎症细胞因子产生,启动或加重全身炎症反应。     

血管紧张素Ⅱ1型受体在急性肺损伤小鼠肺核因子κB和激活蛋白1活化中的作用

目的 了解血管紧张素Ⅱ1型(AT1)受体在LPS诱导的急性肺损伤(ALI)小鼠肺脏NF-κB和激活蛋白1(AP-1)活化中的作用.方法 应用随机数字表法将88只BALB/c小鼠分为对照组8只、LPS组40只、LPS+AT1受体拮抗剂ZD7155组40只.3组小鼠均行气管穿刺.LPS+ZD7155组小鼠腹腔注射ZD7155(10 mg/kg),对照组和LPS组小鼠腹腔注射等体积生理盐水.30 min后,将1 mg/mL LPS分别滴入LPS组和LPS+ZD7155组小鼠气管中(2 mg/kg),对照组小鼠以等体积生理盐水替代LPS经气管滴入.于滴注LPS后1、3、6、12、24 h,留取LPS组和LPS+ZD7155组小鼠肺组织标本;对照组小鼠于滴注后24 h取肺组织标本.采用蛋白质印迹法检测肺组织AT1受体的表达,用凝胶电泳迁移率变化分析法检测肺组织NF-κB和AP-1活性.对各实验结果进行单因素方差分析.结果 LPS组小鼠各时相点肺组织AT1受体蛋白相对表达量较对照组(0.69±0.28)明显升高(F=9.356,P值均小于0.01),6 h时达高峰(3.44±0.90);LPS+ZD7155组各时相点均低于LPS组(F=9.356,P值均小于0.01).LPS组小鼠各时相点肺组织NF-κB活性较对照组(5.47±0.08)显著升高(P=26.443,P值均小于0.05),3 h时达高峰(52.33±3.25);LPS+ZD7155组各时相点肺组织NF-κB活性均明显低于LPS组(F=26.443,P值均小于0.05).LPS组小鼠各时相点肺组织AP-1活性较对照组(2.5±0.4)显著升高(F=34.685,P值均小于0.05),其中6 h时达高峰(73.3±9.5),LPS+ZD7155组各时相点肺组织AP-1活性均明显低于LPS组(F=34.685,P值均小于0.05).结论 AT1受体通过激活NF-κB和AP-1,参与LPS诱导的AL1发生.     

NF-κB圈套技术在小鼠重症急性胰腺炎并发肺损伤中的实验研究

目的 探讨NF-κB圈套技术对小鼠重症急性胰腺炎(SAP)肺损伤的影响.方法 36只BALB/c雌性小鼠随机分为正常对照组、SAP组、NF-κB decoy处理组、错配decoy处理组,每组9只.除正常对照组外,其他组采用雨蛙素联合脂多糖改良法制备小鼠SAP肺损伤模型.制模12 h后处死,采用EMSA法、Western印迹法检测肺脏NF-κB活性和P65蛋白含量的变化;采用逆转录-聚合酶联反应(RT-PCR)法测定肺脏TNF-α、ICAM-1、IL-1 mRNA表达;同时行肺脏病理学损伤评分.结果 12 h后急性胰腺炎组和错配decoy处理组NF-κB活性较正常对照组和圈套技术处理组显著增高;然而除正常对照组外,其他三组间细胞核中NF-κB P65蛋白含量表达没有显著差异;正常对照组下游调控因子TNF-α(0.362±0.043)、ICAM-1(0.198±0.065)、IL-1 mRNA(0.321±0.089)低表达;急性胰腺炎组和错配decoy处理组下游调控因子TNF-α(1.131±0.066;1.031±0.058)、ICAM-1(0.365±0.051;0.385±0.050)、IL-1(0.869±0.110;0.961±0.061)mRNA水平升高(P<0.05);圈套技术处理组下游调控因子TNF-α(0.329±0.059)、ICAM-1(0.186±0.086)、IL-1(0.318±0.136)mRNA水平较上述两组降低(P<0.05).急性胰腺炎组和错配decoy处理组,肺脏组织水肿、炎性浸润方面的病理损伤评分高于正常对照组和圈套处理组(P<0.05).结论 应用圈套技术抑制NF-κB的活性及减少下游炎症介质的表达,可减轻SAP并发的肺组织损伤.     

NF-κB、IL-17与胶原诱导性关节炎大鼠关节滑膜细胞及血清表达的关系

目的:观察核转录因子-κB(NF-κB)、白细胞介素-17(IL-17)在胶原诱导性关节炎(CIA)模型大鼠关节滑膜细胞的表达,探讨其与炎症的关系。方法:将24只6周龄雌性Wistar大鼠随机分为空白对照组和模型对照组,每组12只。模型对照组建立CIA大鼠模型,采用足趾容积、关节炎指数(AI)评价关节炎症,酶联免疫吸附法检测IL-17,免疫印迹法检测滑膜细胞NF-κB/P65、NF-κB/P50和IκBα的表达。结果:CIA模型大鼠足趾容积大于空白对照组,模型对照组大鼠于造模后第14天开始,关节炎指数积分逐渐增加,第28天左右达到高峰。模型对照组大鼠IL-17表达高于空白对照组(P0.01),NF-κB/P65、NF-κB/P50和IκBα蛋白活性明显高于空白对照组(P0.05或P0.01)。结论:CIA模型大鼠滑膜细胞NF-κB活性蛋白增高,IL-17呈高表达,可能与炎症相关。     

创伤小鼠脾细胞核因子-κB的表达及与全身炎症反应综合征发生的关系

目的探讨创伤后不同时相点脾细胞核因子-kappaB(NF-κB)的DNA结合蛋白和NF-κB P65蛋白亚型表达的动态变化.方法采用小鼠双后肢闭合性砸伤+骨折模型,于创伤后1、4、7d处死动物,分离、纯化脾细胞,提取脾细胞核蛋白.用电泳迁移率改变试验(electrophoretic mobility shift assay,EMSA)检测NF-κB的DNA结合活性,用免疫蛋白印变法(Western blotting)检测NF-κB P65蛋白亚型表达.结果NF-κB的DNA结合活性在创伤后1、4、7d表达明显增加.NF-κB P65蛋白亚型在创伤后1、4、7d表达明显增高.结论创伤可明显增强脾细胞NF-κB的DNA结合活性和P65蛋白亚型的表达,在创伤后淋巴细胞活化及全身炎症反应综合征(SIRS)发生、发展过程中可能起重要作用.     

NF-κB、IL-33及sST2在急性胰腺炎合并急性肾损伤中的价值研究

目的:探讨NF-κB、IL-33、sST2在急性胰腺炎(AP)合并急性肾损伤(AKI)患者中的价值。方法:AP患者67例分为轻度(MAP)、中重度(MSAP)、重度(SAP)3组,所有AP患者又分为AKI组和非AKI组。健康志愿者25例。采用流式细胞术检测外周血中NF-κB激活,酶联免疫吸附法测定血清IL-33、sST2水平。结果:MAP组NF-κB p65 24h即有显著激活为(30.72±9.25)%;MSAP组NF-κB p65激活2～3d达到高峰,为(78.48±10.94)%;SAP组NF-κB p65激活变化趋势与MSAP组基本一致,但在AP发病早期NF-κB p65激活更加明显(P 0.05)。对照组各时段NF-κB p65激活不明显(P0.05)。AKI组血清中IL-33水平为(278.3±23.4)pg/mL,非AKI组为(137.5±18.5)pg/mL,均较对照组明显升高,差异有统计学意义(P 0.01)。sST2水平在AKI组和非AKI组也有类似结果。结论:AP合并AKI患者早期外周血中即有NF-κB明显激活,IL-33和sST2高表达,IL-33和sST2有望成为AP合并AKI的早期诊断指标     

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.     

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.