Smad7对高糖介导大鼠肾小管上皮细胞转分化和胶原Ⅰ合成的影响

目的探讨Smad7对高糖介导肾小管上皮细胞转分化和胶原(Col)Ⅰ合成的影响。方法体外培养转染Smad7的大鼠近端肾小管上皮细胞株(NRK52E细胞),分为强力霉素(Dox)诱导组和未加强力霉素的对照组。前者予Dox诱导24 h后,给予高糖刺激;后者不加Dox诱导。采用免疫细胞化学方法检测磷酸化(p)-Smad2/3核转位情况;RT-PCR检测Smad7的表达;Western印迹方法检测不同时间点Smad7、α-SMA、E-钙黏蛋白(cadherin)和ColⅠ蛋白的表达水平。结果成功构建了Dox调控的可上调Smad7表达的NRK52E细胞。NRK52E细胞在基础状态下可表达低水平p-Smad2/3(16．1％),与未加Dox的对照组比较,Dox诱导组可显著抑制高糖刺激的NRK52E细胞TGF-β受体调控信号蛋白Smad2/3的活化和核转位(30．3％比58．5％, P<0．01)。上调表达Smad7可显著抑制高糖介导的NRK52E细胞α-SMA和ColⅠ蛋白的表达;逆转高糖介导的NRK52E细胞E-cadherin蛋白的下调表达。结论基因转染上调表达Smad7可通过TGF-β受体调控信号蛋白Smad2/3的活化和核转位而阻抑高糖介导的肾小管上皮细胞转分化及细胞外基质的合成。     

终末期糖基化终产物通过转化生长因子依赖和非依赖途径介导NRK52E细胞转分化和胶原Ⅰ的合成

目的探讨终末期糖基化终产物（AGEs）介导肾小管上皮细胞转分化和胶原（Col）Ⅰ合成的分子机制。方法体外培养正常大鼠近端肾小管上皮细胞系（NRK52E），应用自制的AGE-牛血清白蛋白（BSA）刺激NRK52E细胞。免疫细胞化学方法检测不同时间磷酸化（P）Smad2／3核转位情况。ELISA方法检测细胞培养上清TGF-β1的水平。RT-PCR方法检测α-平滑肌肌动蛋白（SMA）、E-钙黏着糖蛋白（cadherin）和ColⅠmRNA表达。Western印迹检测α-SMA、E-cadherin和ColⅠ蛋白的表达。同时观察TGF-β1中和抗体对AGE-BSA上述效应的阻断作用。结果基础状态下，NRK52E细胞存在低水平p-Smad2／3核表达（16％）。与BSA对照组比较，AGE—BSA以时间依赖方式上调NRK52E细胞p-Smad2／3核转位，其高峰出现在30min（68％比30.5％，P〈0．01）和24h（76％比31．3％，P〈0．01）。AGE—BSA显著上调α-SMA和ColⅠmRNA和蛋白表达；下调E-cadherin mRNA和蛋白的表达；并能促进NRK52E细胞合成和分泌TGF-β1。TGF-β1中和抗体能明显抑制AGE—BSA介导的24hp-Smad2／3核转位（25．2％，P〈0．01），但不能阻抑30min活化高峰；能明显抑制AGE-BSA介导的α-SMA和ColⅠmRNA和蛋白表达．以及显著地上调E-cadherin mRNA和蛋白的表达。结论AGEs通过TGF-β依赖和非依赖途径诱导肾小管上皮细胞Smads信号通路活化，促进其向肌成纤维母细胞转分化和ColⅠ的合成。     

虫草素通过下调TGF-β抑制高糖诱导的大鼠肾小管上皮细胞转分化

目的：探讨虫草素对高糖诱导的大鼠肾小管上皮细胞转分化的影响。方法：体外培养大鼠近端肾小管上皮细胞株（NRK52E细胞株）,分为正常对照组（葡萄糖5.5 mmol/L,NG组）、高糖组（葡萄糖30 mmol/L,HG组）、高糖＋虫草素组（葡萄糖30 mmol/L＋虫草素10μg/ml,HG＋C组）。分别于刺激12 h,24 h,48 h后收集细胞。应用定量RT-PCR测定NRK52E TGF-β,E-cadherin,α-SMA mRNA的表达;Western印迹方法检测TGF-β、E-cadherin、α-SMA蛋白的表达。结果：高糖刺激后NRK52E细胞的TGF-β和α-SMA mRNA及蛋白表达明显高于正常糖组（P〈0.01）,而虫草素组TGF-β和α-SMA mRNA及蛋白表达显著低于高糖组（P〈0.05）;高糖诱导的NRK52E细胞E-cadherin mRNA及蛋白水平明显降低（P〈0.01）;而虫草素组NRK52E细胞E-cadherin mRNA及蛋白水平显著高于高糖组（P〈0.05）。结论：虫草素可以明显抑制高糖诱导的大鼠肾小管上皮细胞转分化,其机制可能是通过下调TGF-β实现。     

Par-3蛋白在转化生长因子?茁1介导的大鼠肾小管上皮细胞转分化中的作用

目的 观察转化生长因子（TGF)β1诱导的正常大鼠近端肾小管上皮细胞（NRK52E）转分化（EMT）过程中细胞极性蛋白Par-3的表达及上调Par-3蛋白表达对TGF-β1诱导NRK52E细胞转分化进程的影响。 方法 应用TGF-β1 (10 μg/L)刺激NRK52E细胞，采用RT-PCR、Western印迹和免疫荧光方法分别检测E-钙黏蛋白(E-cadherin)、α-平滑肌肌动蛋白（α-SMA）、Par-3 mRNA和蛋白的表达；应用Lipofectmine 2000将pKH3-HA-Par-3质粒瞬时转染NEK52E细胞，采用Western印迹观察上调表达Par-3对上述指标的影响。 结果 TGF-β1刺激后，NRK52E细胞α-SMA蛋白和mRNA水平上调，E-cadherin蛋白和mRNA的表达下调；Par-3蛋白表达呈时间依赖模式下调，72 h TGF-β1刺激组与对照组比较，差异有统计学意义（P < 0.05）。但Par-3 mRNA水平在各时间点差异均无统计学意义（P > 0.05）。脂质体转染外源性质粒pKH3-HA-Par-3上调表达Par-3可显著抑制TGF-β1诱导NRK52E细胞α-SMA蛋白的上调表达；逆转E-cadherin蛋白的下调表达。 结论 在TGF-β1诱导NRK52E细胞转分化进程中细胞极性Par-3蛋白表达下调，基因转染上调表达Par-3可部分减轻EMT的程度，提示Par-3蛋白在TGF-β1诱导的肾小管上皮细胞转分化和肾脏纤维化中可发挥保护性作用。     

黄芪通过c-met调控TGF-β1诱导的肾小管上皮细胞转分化

AB 目的：探讨黄芪对TGF-β1诱导的肾小管上皮细胞转分化及细胞外基质分泌的作用及机制。方法：体外培养正常大鼠肾小管上皮细胞（NRK52E）,应用倒置相差显微镜观察NRK52E细胞形态学变化;免疫组织化学染色法及实时荧光定量PCR法检测α-平滑肌肌动蛋白（α-SMA）,肝细胞生长因子HGF受体（c-met）的表达;ELISA法定量检测细胞上清液中胶原Ⅰ（Col-Ⅰ）,胶原Ⅲ（Col-Ⅲ）和纤维黏连蛋白（FN）的水平。结果：TGF-β1可诱导肾小管上皮细胞肌成纤维细胞转分化（TEMT）,TGF-β1诱导组细胞肥大、拉长,呈长梭形,α-SMA表达明显增强,Col-Ⅰ、Col-Ⅲ和FN分泌增加（P〈0.05）。加入不同浓度黄芪后,细胞形态接近正常肾小管上皮细胞形态,α-SMA表达、Col-Ⅰ、Col-Ⅲ和FN分泌均较TGF-β1诱导组明显抑制（P〈0.05）,c-met表达较TGF-β1诱导组增加（P〈0.05）且呈剂量依赖性。结论：TGF-β1可以诱导肾小管上皮细胞肌成纤维细胞转分化,增加细胞外基质成分Col-Ⅰ、Col-Ⅲ和FN的分泌;黄芪能够抑制TGF-β1诱导的NRK52E细胞转分化以及细胞外基质的分泌;黄芪抑制细胞转分化的机制可能与其增强c-met的表达有关。     

红细胞生成素对高糖诱导下肾小管上皮细胞转分化的影响

目的 探讨红细胞生成素（EPO）对高糖诱导下的肾小管上皮细胞转分化的影响。 方法 体外培养人肾小管上皮细胞株（HK-2细胞）,分为正常对照组、渗透浓度对照组、高糖组、高糖＋EPO（5 U/ml）组和高糖＋EPO（10 U/ml）组。RT-PCR法检测各组细胞α平滑肌肌动蛋白（α-SMA）、转化生长因子β1（TGF-β1）、Smads信号蛋白2（Smad2）及整合素连接激酶（ILK）的mRNA表达。细胞免疫荧光法检测细胞TGF-β1及α-SMA的蛋白表达。 结果 RT-PCR结果显示,相对于对照组,高糖组细胞α-SMA、TGF-β1、Smad2、ILK的mRNA表达均显著上调（P ＜ 0.01）。细胞免疫化学也显示,高糖组TGF-β1和α-SMA的蛋白表达较对照组显著上调（P ＜ 0.01）,而高糖＋EPO（5 U/ml）组和高糖＋EPO（10 U/ml）组上述指标的表达均显著低于高糖组（均P ＜ 0.01）。 结论 EPO能抑制高糖诱导的肾小管上皮细胞转分化,可能与其抑制TGF-β1、Smad2及ILK表达有关。     

囊泡型H+-ATP酶B亚基在转化生长因子β1致肾小管上皮细胞转分化中的变化及其意义

目的 探讨在转化生长因子（TGF）β1致大鼠肾小管上皮细胞（NRK52E）发生上皮细胞向间质细胞转分化（EMT）过程中囊泡型H+-ATP酶（V-ATPase）B亚基的变化及其可能意义。 方法 NRK52E细胞无血清培养后予TGF-β1（10 μg/L）刺激不同时间（0、6、12、24、48、72 h）,应用实时定量PCR、Western印迹、免疫荧光技术检测?琢平滑肌肌动蛋白（?琢-SMA）、E钙黏素（E-cadherin）、V-ATPase B亚基（B1、B2）mRNA、蛋白表达及分布的变化。 结果 TGF-β1刺激NRK52E细胞48 h后?琢-SMA mRNA及蛋白表达显著上调,E-cadherin mRNA及蛋白表达显著下调,同时V-ATPase B2亚基mRNA及蛋白表达也显著增加（均P < 0.05）。但是B1亚基在细胞内表达很低,刺激后也未见显著变化。免疫荧光也显示V-ATPase B2亚基在细胞内的分布明显增加并向胞膜聚集。 结论 在NRK52E内主要分布的是V-ATPase B2亚基。TGF-β1刺激NRK52E EMT过程中V-ATPase B2亚基表达显著增加,这提示B2亚基可能参与肾小管EMT过程。     

Erbin在肾间质纤维化中的表达和作用

目的 探讨Erbin在肾脏间质纤维化中表达量的变化及上调Erbin对转化生长因子β1（TGF-β1）诱导大鼠近端肾小管上皮细胞（NRK52E）转分化的影响。 方法 体内实验采用SD大鼠5/6肾切除法建立肾纤维化动物模型,收集并检测各组血清中Scr、BUN水平;Masson染色观察肾间质纤维化程度;免疫组化及Western印迹检测Erbin的分布与表达。 体外实验采用TGF-β1（10 μg/L）刺激NRK52E细胞72 h建立上皮细胞-间充质转分化（EMT）细胞模型;免疫荧光及Western印迹法检测E钙黏蛋白（E-cadherin）和α平滑肌肌动蛋白（α-SMA）的表达变化;RT-PCR及Western 印迹法检测Erbin的表达变化。用脂质体2000将质粒 Prk5-myc-Erbin瞬时转染至NRK52E细胞,Western印迹法观察上调Erbin表达后对上述各种指标的影响。 结果 （1）假手术组大鼠肾功能正常[Scr（33.96±7.28） μmol/L、BUN（8.11±2.55） mmol/L],Masson染色未见肾间质纤维化,Erbin在肾小管表达较少;模型组大鼠Scr [（140.52±61.11） μmol/L]、BUN[（34.23±7.66） mmol/L] 均显著高于假手术组（均P < 0.05）,肾间质可见明显纤维化,Erbin 在肾小管表达也明显增加,是假手术组的2.9倍（P < 0.01）。（2）正常NRK52E 细胞表达E-cadherin,少量表达Erbin和α-SMA。TGF-β1刺激后,NRK52E细胞E-cadherin表达显著减少,Erbin和α-SMA则表达增加（均P < 0.05）;而转染质粒Prk5-myc-Erbin可逆转TGF-β1诱导的NRK52E细胞E-cadherin表达下调,并可抑制α-SMA表达上调（均P < 0.05）。 结论 Erbin在肾间质纤维化中表达增加,上调Erbin表达可抑制TGF-β1诱导NRK52E发生EMT, 提示Erbin在肾脏纤维化中可发挥保护作用。     

松弛素对高糖诱导的肾小管上皮细胞转分化及分泌细胞外基质的影响

目的:观察人松弛素(Relaxin)对高糖培养人肾小管上皮细胞(HK-2)转分化、分泌细胞外基质的影响。方法:实验分组:正常糖组:含5.5 mmol/L葡萄糖;高糖组:含30 mmol/L葡萄糖;高渗组(甘露醇组);高糖+松弛素干预组;ELISA法检测细胞上清中TGF-β1、细胞胶原(ColⅠ)、纤连蛋白(FN)的表达。免疫印迹技术(Western blot)检测α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)表达,确定肾小管上皮细胞表型转化情况。结果:与正常糖组相比,高糖组肾小管上皮细胞分泌ColⅠ、FN、TGF-β1显著增加,在高糖培养基中加入人松弛素干预后可显著抑制由高糖诱导的ColⅠ、FN、TGF-β1的高表达,降低α-SMA表达,抑制肾小管上皮细胞转分化。结论:松弛素能抑制高糖诱导HK-2细胞分泌细胞外基质,抑制HK-2细胞转分化,具有抗纤维化作用。     

血管紧张素1-7对高糖诱导人肾小管上皮细胞转分化的影响及其机制

目的 研究血管紧张素1-7（Ang 1-7）对高糖诱导人肾小管上皮细胞（HK-2）转分化的影响及其可能机制。 方法 培养HK-2细胞分组如下：对照组（N组）、高糖组（H组）、高糖+Ang 1-7组（A组）、高糖+Ang 1-7+A779组（D组）、高糖+吡格列酮组（P组）。Western印迹检测各组HK-2细胞过氧化物酶体增殖物激活受体γ（PPAR-γ）及α平滑肌肌动蛋白（α-SMA）的蛋白表达;实时定量PCR检测HK-2细胞PPAR-γ及α-SMA的mRNA表达;免疫荧光检测α-SMA表达。 结果 Ang 1-7可上调高糖刺激下HK-2细胞PPAR-γ蛋白及mRNA表达（P < 0.05）;抑制高糖刺激的α-SMA蛋白及mRNA表达（P < 0.05）。这种作用与PPAR-γ激动剂吡格列酮类似。给予Mas受体抑制剂A779后,Ang 1-7的上述作用可被部分抑制。 结论 Ang 1-7在体外可通过上调PPAR-γ表达,从而部分抑制高糖诱导的α-SMA表达,实现其抑制转分化的作用,而这种作用部分通过Mas受体所介导。     

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.