JAK-STAT通路在小鼠单侧输尿管梗阻模型肾间质纤维化中的作用

目的 探讨Janus蛋白酪氨酸激酶-信号转导子和转录激活子(JAK-STAT)通路在小鼠单侧输尿管梗阻(UUO)模型.肾间质纤维化过程中的作用.方法 选用30只雄性Balb/c小鼠建立小鼠UUO模型(n=24)和假手术小鼠(n=6),术后第1、4、7和14天检测JAK-STAT磷酸化情况.另把18只雄性Balb/c小鼠随机分为假手术组、UUO模型组和治疗组,每组各6只.治疗组在建模前2 h开始给予选择性JAK2抑制剂AG490治疗,每天1次;模型组仅注射溶媒.术后第14天处死动物.组织学评估肾小管损伤和.肾间质纤维化程度;免疫组化检测肾脏巨噬细胞浸润和α-SMA表达;RT-PCR检测Ⅲ型胶原和单核细胞趋化蛋白(MCP)1 mRNA表达;Western印迹检测JAK2和STATl磷酸化.结果 JAK2-STAT1在UUO模型中被激活,其磷酸化水平与病情、肾小管组织学损害以及.肾间质纤维化相一致.AG490能显著抑制JAK2和STAT1的磷酸化(P＜0.01).AG490治疗显著减轻肾小管损害[(21.7±1.7)%比(49.4±1.0)%]和肾间质纤维化(1.0±0.1比2.3±0.2)、α-SMA表达(0.9±0.1比2.1±0.2)和巨噬细胞积聚[(13.3±1.6)细胞/HPF比(34.4±1.0)细胞/HPF](均P＜0.01).AG490治疗显著抑制Ⅲ型胶原和MCP-1 mRNA表达.结论 JAK-STAT信号通路在肾小管间质炎性反应和纤维化中发挥重要作用.     

L-精氨酸在梗阻性肾病中逆转肾间质纤维化的研究

目的:探讨L-精氨酸恢复梗阻肾肾功能和抗肾小管间质纤维化的作用.方法:建立大鼠单侧输尿管梗阻模型(UUO),以免疫组织化学染色法对侵入肾内单核/巨噬细胞数、Ⅳ型胶原(CODⅣ)及其α-平滑肌肌动蛋白(α-SMA)进行分析;逆转录多聚酶链反应对大鼠COL-ⅣmRNA,α-SMA mRNA及金属蛋白酶组织抑制因子1(TIMP-1)mRNA转录量分析;对尿液中尿氮浓度的改变进行分析.结果:UUO内侵入单核/巨噬细胞数,α-SMA沉积,COL-Ⅳ沉积及α-MA mRNA、COL-ⅣmRNA及TIMP-1 mRNA含量减少;提示UUO纤维变性减少.同时UUO中尿氮浓度升高,差异具统计学意义(P<0.05).结论:L-精氨酸具有阻止UUO肾小管间质纤维化和改善肾功能的作用,其作用与增加氧化亚氮(NO)的形成这一机制有关.     

金属蛋白酶组织抑制剂1在大鼠肾小管间质损害中的表达及其意义

目的 观察单侧输尿管梗阻(UUO)大鼠模型中金属蛋白酶组织抑制剂1(TIMP-1)在肾小管间质中的表达部位、动态变化及其与肾小管问质损害的关系。方法 制备UUO大鼠模型,采用免疫组织化学方法检测UUO术后第1、3、5、7、14天肾小管间质中TIMP-1、α-平滑肌肌动蛋白(SMA)、增殖细胞核抗原(PCNA)和单核巨噬细胞抗原(ED)-1的表达及其与输尿管梗阻后肾小管间质损害的关系。结果 UUO术后第1天肾间质可见少量TIMP-1表达细胞,第3～7天TIMP-1表达明显增加,主要表达于肾小管上皮细胞和肾间质。UUO术后第3天肾小管PCNA表达达高峰,随后下降,而肾间质PCNA水平于第7～14天仍较高。UUO术后第3天肾间质成纤维细胞及肾小管上皮细胞可检出α-SMA表达并随时间递增。α-SMA阳性面积与肾间质相对面积成正相关(r=0.924,p<0.01)。TIMP-1表达与间质相对面积(r=0.835,P<0.05)及α-SMA阳性面积(r=0.922,P<0.01)成正相关。结论 TIMP-1蛋白质于肾小管间质病变早期表达于肾小管间质,早于肾间质纤维化出现,其表达量与肾间质α-SMA表达及肾间质相对面积呈正相关并随病变进展逐渐增加。TIMP-1在肾小管上皮细胞和问质细胞的高表达及肾小管上皮细胞和间质细胞增殖可能参与介导UUO术后肾小管间质损害。     

转化生长因子-β1 在梗阻性肾病大鼠肾小管间质纤维化中的作用

目的探讨转化生长因子 (TGF) -β1在梗阻性肾病(UUO)大鼠梗阻肾中致肾小管间质进行性纤维化的作用.方法成年SD大鼠制成UUO模型,在梗阻后3、7、10、14 d处死.免疫组织化学染色法对其肾内α-平滑肌肌动蛋白(SMA)沉积量及侵入肾内的单核巨噬细胞数进行分析;逆转录多聚酶链反应(RT-PCR)对大鼠TGF-β1 mRNA、金属蛋白酶组织抑制剂(TIMP)-1 mRNA及IV型胶原(Col-IV) mRNA转录量进行分析.结果随梗阻时间延长,侵入梗阻肾内单核巨噬细胞数、α-SMA沉积、Col-IV mRNA及TIMP-1 mRNA含量增加;示肾小管间质存在进行性纤维化.同时TGF-β1 mRNA含量明显增加,差异统计学意义(P<0.05).结论 TGF-β1促使梗阻性肾病大鼠肾小管间质进行性纤维化.     

氟伐他汀对UUO大鼠肾间质单核细胞趋化蛋白-1表达及巨噬细胞浸润的影响

目的观察氟伐他汀对单侧输尿管梗阻大鼠肾间质单核细胞趋化蛋白-1(MCP-1)表达和巨噬细胞浸润的影响,探讨其抗纤维化机制。方法90只SD雌性大鼠随机分成假手术(SOR)组、单侧输尿管梗阻术(UUO)模型组和UUO+氟伐他汀治疗组(T-UUO,氟伐他汀20mg·kg-1·d-1)。于术后第1、4、7、10、14d分别处死各组大鼠。用HE及Masson染色动态观察肾脏病理变化,免疫组织化学法测定MCP-1、单核巨噬细胞抗原(ED-1)的表达。结果UUO模型组肾小管-间质MCP-1与ED-1表达较SOR组增加(P<0.05);在术后各时间点,T-UUO组大鼠肾小管-间质MCP-1、ED-1的表达及肾间质胶原相对面积较UUO模型组显著减少,但/仍高于SOR组(P<0.05)。结论氟伐他汀可通过降低MCP-1表达、减少单核/巨噬细胞浸润以抑制肾间质纤维化。     

梗阻性肾病大鼠肾小管间质进行性纤维化的监测

目的:探讨梗阻性肾病肾小管间质进行性纤维变性的发展过程。方法:建立大鼠单侧输尿管梗阻模型(UUO),采用免疫组化染色方法测其双侧肾形态学改变及胶原Ⅳ蛋白和α平滑肌肌动蛋白(α-SMA)的沉积;应用RT-PCR定性和半定量的方法测其金属蛋白酶组织抑制剂1(TIMP-1)mRNA、胶原ⅣmRNA的表达。结果:随着梗阻时间延长,梗阻侧肾脏肾小管间质变宽,肾小球无明显变化。梗阻肾内的胶原Ⅳ蛋白和α平滑肌肌动蛋白沉积增加,差异有统计学意义(P<0.05)。胶原ⅣmRNA、TIMP-1mRNA表达明显增加,差异有统计学意义(P<0.05);对侧肾脏各项指标变化差异无显著性。结论:该模型稳定可靠,能较好地体现梗阻性肾病中肾小管间质纤维化进行性发展过程。     

糖肾方改善单侧输尿管梗阻小鼠肾间质纤维化的机制研究

目的:观察糖肾方对单侧输尿管梗阻(UUO)小鼠肾间质纤维化的作用,并初步探讨其机制。方法:45只雄性C57BL/6小鼠随机分为假手术组(Sham)、UUO模型组(UUO)、糖肾方组(TSF);预先给药7 d,除Sham组外其余各组行UUO手术,术后7 d取肾组织进行HE染色及Masson染色观察肾组织病理改变,免疫组化染色检测α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、Ⅰ型胶原(Collagen typeⅠ,ColⅠ)和Ⅲ型胶原(Collagen typeⅢ,ColⅢ)表达,Western Blot法检测转化生长因子-β_1(transforming growth factor-β_1,TGF-β_1)、E-钙连素(E-cadherin)和波形蛋白(vimentin)表达。结果:与Sham组比,UUO组小鼠肾小管间质损伤评分及纤维化面积百分比均显著升高;与UUO组比,TSF组肾小管间质损伤评分及纤维化面积百分比均显著降低。免疫组化与Western blot结果显示,与Sham组比,UUO组小鼠肾组织TGF-β_1及ColⅠ、ColⅢ表达水平显著升高;肾小管上皮细胞间质转分化(epithelial-mesenchymal transition,EMT)标志性分子α-SMA和vimentin蛋白表达水平明显升高,E-cadherin蛋白表达水平明显降低,TSF可显著逆转UUO小鼠肾组织上述蛋白表达。结论:糖肾方可改善UUO小鼠肾间质纤维化,其机制与其抑制TGF-β_1,减少EMT发生有关。     

依普利酮对大鼠单侧输尿管梗阻模型肾间质纤维化的影响

目的：研究依普利酮对大鼠单侧输尿管梗阻（UUO）模型肾间质纤维化的影响,探讨依普利酮的抗肾间质纤维化作用机制。方法：42只雄性Wistar大鼠随机分成假手术（SO）组、UUO组和UUO＋依普利酮治疗组（T-UUO组,依普利酮100mg.kg-1.d-1）。于术后7d、14d分别处死各组7只大鼠。免疫组织化学法测定α-平滑肌肌动蛋白（α-smoothmuscle actin,α-SMA）、单核细胞趋化蛋白-1（monocyte chemoattractant protein-1,MCP-1）、单核细胞/巨噬细胞-1（monocytes/macrophages-1,ED-1）,及增殖细胞核抗原（proliferative cell nuclear antigen,PCNA）的表达。结果：UUO组肾间质α-SMA、MCP-1、ED-1、PCNA的表达较SO组增加（P〈0.05）;在术后各时间点,使用依普利酮治疗的T-UUO组大鼠肾间质α-SMA、MCP-1、ED-1、PCNA的表达较UUO组显著减少（P〈0.05）,但仍高于SO组（P〈0.05）。结论：依普利酮可通过降低α-SMA和MCP-1表达、抑制单核/巨噬细胞浸润和和系膜细胞增生,减轻肾间质纤维化。     

绞股蓝总皂苷防治单侧输尿管结扎大鼠肾间质纤维化的实验研究

目的探讨绞股蓝总皂苷(GPs)对单侧输尿管结扎(UUO)大鼠肾组织结缔组织生长因子(CTGF)表达及肾间质纤维化的影响。方法采用UUO大鼠模型,将大鼠随机分为3组假手术组、模型组、GPs组。假手术组和模型组仅给予标准饲料30g,GPs组于术前3d至术后9d每天给予GPs200mg·kg-1·d-1灌胃,第9d处死各组大鼠。免疫组化法检测各组肾组织CTGF、转换生长因子β1(TGF-β1)和α-平滑肌肌动蛋白(α-SMA)的表达;RT-PCR方法检测各组CTGFmRNA含量;Masson染色评定各组肾小管间质损害程度。结果模型组CTGF、TGF-β1、α-SMA的表达及肾小管间质损伤指数明显高于假手术组(P<0.01),而GPs组各项指标明显低于模型组(P<0.01)。各项指标作相关分析,CTGF与肾小管间质损伤指数(r=0.788,P<0.01)、TGF-β1(r=0.879,P<0.01)、α-SMA(r=0.940,P<0.01)为正相关关系。结论绞股蓝总皂苷可以抑制肾纤维化时结缔组织生长因子表达,从而遏制肾纤维化的进展。     

青藤碱对UUO小鼠肾组织间质纤维化与炎症因子表达的干预作用

目的：通过抗风湿药青藤碱对UUO小鼠肾组织α-平滑肌肌动蛋白（α-smooth muscle actin,α-SMA）、炎症介质细胞间黏附分子（intercellular adhesion molecule1,ICAM-1）、单核细胞趋化因子（monocyte chemoattractant protein1,MCP-1）表达的影响,探讨其防治肾间质纤维化作用及其机制。方法：实验采用小鼠单侧输尿管结扎（UUO）模型,用不同剂量青藤碱进行干预,用血管紧张素受体抑制剂蒙诺作为对照。肾脏病理用HE和Masson染色;肾组织α-SMA表达采用免疫组化;ICAM-1蛋白质表达采用Western-blotting方法检测;MCP-1基因表达采用逆转录-聚合酶链式反应（RT-PCR）方法。结果：UUO模型组小鼠肾间质纤维化程度以及肾组织α-SMA的表达较假手术组显著增高,肾小管间质中炎细胞浸润亦较假手术组显著增强;青藤碱各治疗组肾间质纤维化程度、α-SMA和ICAM-1蛋白、MCP-1基因表达均显著低于模型组;蒙诺治疗亦可显著降低肾间质纤维化程度和肾组织α-SMA的表达,但对于炎细胞浸润和炎症因子抑制作用显著较青藤碱弱。而且未见其具有抑制ICAM-1表达的作用。结论：抗风湿药青藤碱可显著抑制肾间质纤维化和肌成纤维细胞的积聚,可能与其显著抑制肾组织炎症因子的表达及炎细胞浸润有关。     

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.     

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.