血管新生抑制剂TNP-470对鼠ACHN肾细胞癌增殖与凋亡的影响

目的 :探讨血管新生抑制剂TNP 4 70对ACHN肾细胞癌增殖与凋亡状态的影响。方法 :采用TNP 4 70 (4 0mg·kg-1·0 .2ml-1)皮下注射治疗ACHN肾细胞癌荷瘤裸鼠 ,观察肿瘤生长情况 ,进行细胞增殖与细胞凋亡的研究。结果 :TNP 4 70治疗组与对照组相比 ,ACHN肾癌生长明显减慢 ,肿瘤细胞凋亡指数明显增加 (P <0 .0 1) ,增殖指数无显著变化 (P >0 .0 5 )。肿瘤体积与凋亡指数间存在负相关 (r =- 0 .85 4 0 ,P <0 .0 1)。结论 :TNP 4 70对ACHN肾癌有显著的抑制肿瘤生长作用 ,可能与肾癌细胞凋亡增加有关     

生长抑素对鼠大部肝切除术后肝再生的影响

目的　探讨生长抑素对肝切除术后肝再生的影响。　方法　 6 0只SD大鼠随机分为对照组及生长抑素组 ,按Higgins方法行 70 %肝切除术 ,术后给药并分批于术后 6、2 4、48、72、96h处死 ,作如下比较 :①残肝肝重 ;②增殖细胞核抗原 (PCNA)标记指数 ;③图像定量分析测量PCNA阳性产物面积。　结果　与对照组比较 ,生长抑素组残肝肝重在术后 48、72、 96h显著降低 (P <0 .0 5 ) ,PCNA标记指数、PCNA阳性产物面积在术后 2 4、48、72h显著降低 (P <0 .0 5 ) ,且以 2 4、 48h最为明显 (P <0 .0 1)。　结论　生长抑素能抑制肝再生 ,且肝再生程度越强 ,抑制效应越明显     

谷氨酰胺强化的肠内营养对化疗大鼠肠屏障的影响

目的　评价谷氨酰胺强化的肠内营养对氟尿嘧啶 (5 Fu)化疗大鼠肠屏障的影响。方法　 30只胃造瘘术后的Wistar大鼠随机分为饲料组 (A组 )、肠内营养组 (B组 )和谷氨酰胺强化的肠内营养组 (C组 ) ,每组10只。术后第 4天用 5 Fu化疗 ,比较它们的体重变化、小肠和结肠结构、血浆谷氨酰胺水平、肠通透性 (L/M )及细菌移位率 (BTR)等指标。结果　B组体重丢失 (- 6 6± 5 2 )g (P <0 0 1) ,C组体重无明显变化 ;C组小肠结构优于B组 (P <0 0 1)与A组相似 (P >0 0 5 ) ,但C组结肠结构不及A组 (P <0 0 1)而与B组相似 (P >0 0 5 )。化疗后与A组比 ,C组L/M无明显变化 (P >0 0 5 ) ,而B组上升 (P <0 0 1) ;C组细菌移位率 (30 % )低于B组 (70 % ) (P <0 0 5 ) ,与A组 (2 0 % )无显著差异 (P >0 0 5 )。结论　谷氨酰胺强化的肠内营养能保护 5 Fu化疗大鼠的肠屏障。     

Valsartan对糖尿病肾病肾保护作用的实验研究

目的 :探讨血管紧张素Ⅱ受体拮抗剂 (AT1RA)Valsartan对糖尿病大鼠肾脏基质金属蛋白酶 - 2 (MMP- 2 )及其抑制物 (TIMP - 2 )表达的影响。方法 :大鼠随机分为正常对照组 (A组 )、糖尿病组 (B组 )及治疗组 (C组 ) ,大鼠腹腔单剂量注射链脲佐菌素 (streptozotocin ,STZ) 6 5mg/kg建立糖尿病动物模型。治疗组给予Valsartan(缬沙坦 ) 10mg·kg-1·d-1灌胃。第 3周、第 6周各组分别宰杀 6只 ,检测肌酐清除率、尿白蛋白排泄率及肾重 /体重 ,免疫组织化学染色检测肾小球MMP - 2、TIMP - 2、纤维连接蛋白和Ⅳ型胶原表达。结果 :治疗组肌酐清除率 (P <0 .0 5 )、尿白蛋白排泄率 (P <0 .0 5 ,P <0 .0 1)及肾重 /体重 (P <0 .0 5 )均低于糖尿病组。免疫组织化学染色可见糖尿病大鼠肾小球TIMP - 2、纤维连接蛋白和Ⅳ型胶原表达明显增加 (P <0 .0 5 ,P <0 .0 1)。在治疗组 ,上述明显增加的表达均受到明显抑制 (P <0 .0 5 )。MMP - 2在糖尿病大鼠肾小球的表达明显被抑制 (P <0 .0 1) ,治疗组其表达明显增加 (P <0 .0 5 )。结论 :Valsartan通过上调糖尿病大鼠肾小球MMP - 2表达、下调TIMP - 2表达 ,对糖尿病大鼠肾脏病变有部分保护作用。     

司坦唑醇预防维甲酸致大鼠骨损害的作用

目的 利用骨密度、骨生物力学、骨组织形态计量学等方法探讨司坦唑醇对维甲酸致骨损害的预防作用。方法 4月龄的SPF级雌性SD大鼠24只，随机分成正常对照组、维甲酸组、司坦唑醇组。正常对照组给予溶剂对照溶液，维甲酸组给予维甲酸70 mg ?kg-1?d-1，司坦唑醇组给予维甲酸70 mg? kg-1?d-1和司坦唑醇0.5 mg? kg-1?d-1。大鼠每次均按5 ml ?kg-1灌胃给药，连续给药28天。实验结束后取大鼠右侧股骨进行骨密度和生物力学参数测量，取右侧胫骨上段和中段进行骨组织 形态计量学测量。结果 与正常对照组比较，维甲酸组大鼠股骨骨密度降低10. 2% (P <0. 01)，生物力学参数弹性载荷、最大载荷、断裂载荷、刚性系数、弯曲能量分别降低39. 1%、32. 9%、36. 4%、40. 2%、38. 0%( P <0. 01)，胫骨上段松质骨静态参数骨组织总面积、骨小梁面积、骨小梁周长分别降低31. 6%、40. 0%、36. 2% (P <0. 01)，动态参数标记周长百分数(％ L. Pm)、骨形成率(BFR/TV、BFR/ BS、BFR/BV)分别降低57. 1%、69. 9%、62. 0%、65. 8% (P <0.01)。胫骨中段皮质骨静态参数（骨组织总面积、皮质骨面积)和骨外膜动态参数均降低，而骨内膜动态参数增强。与维甲酸组比较，司坦唑醇组股骨弹性载荷、刚性系数、弯曲能量分别增加22. 2%、22. 9%、17. 7%(P <0. 05)，而骨密度、胫骨上段松质骨和中段骨皮质骨组织形态计量学参数均无明显变化。结论 司坦唑醇可部分改善维甲酸所致大鼠骨损害。     

大鼠小肠移植后淋巴管重建对他克莫司药代动力学的影响

目的　研究大鼠小肠移植后淋巴管重建对他克莫司 (FK5 0 6 )吸收、转运等药代动力学的影响。方法　近交系雄性BrownNorway (BN)大鼠为供者 ,Lewis (LEW )大鼠为受者。将实验大鼠随机分为两组。A组 (n =12 ) :LEW大鼠在异位双造口小肠移植后 ,立即作淋巴管重建术 (LR)。B组 (n =12 ) :LEW大鼠在异位双造口小肠移植后 ,不作LR。两组术后均给予FK5 0 6 ,用量为 0 .5mg/kg ,经移植肠腹壁造口注入 ,1次 /d。分别在小肠移植术后 1、4、7、14d给予FK5 0 6后1.2、2、3h ,取静脉血约 0 .5ml,用微粒子免疫分析仪进行FK5 0 6全血质量浓度测定。结果　术后 1、4、7d给药后各时段 ,B组大鼠血浆FK5 0 6水平均显著低于A组 (P <0 .0 5 )。术后第 14d ,B组给药后各时段的血浆FK5 0 6水平仅轻度低于A组 ,但在给药后 1.2h ,差异仍有显著性 (P <0 .0 5 )。结论　大鼠异位小肠移植后淋巴管立即重建 ,对FK5 0 6的吸收和转运能力显著提高。     

真武汤对肾病综合征模型大鼠HMGB1/Beclin-1信号通路影响及机制研究

目的:探究真武汤对肾病综合征模型大鼠HMGB1/Beclin-1信号通路及炎性因子的影响。方法:将90只雄性Wistar大鼠随机分为6组,即空白对照组、模型对照组、阳性对照组、真武汤治疗高、中、低剂量组。除空白对照组注射等体积生理盐水外,其余各组均通过注射盐酸阿霉素制作肾病综合征大鼠模型。造模结束后第5天,肾病综合征高、中、低剂量组分别以真武汤12 g/kg、6 g/kg、3 g/kg剂量进行给药。阳性对照组给予泼尼松,剂量为0. 2 g/kg。空白对照组及模型对照组给予等容积蒸馏水5 ml灌胃,所有大鼠每天均给药1次,连续给药3周。末次给药24 h后,酶联免疫吸附法(ELISA)测定大鼠外周血肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白介素4(interleukin-4,IL-4)、白介素8(interleukin-8,IL-8)表达水平; HE染色观察大鼠肾组织病理变化;蛋白免疫印迹法(Western blot)测定各组大鼠肾组织中HMGB1/Beclin-1蛋白及相关蛋白的表达变化。结果:模型对照组大鼠外周血中TNF-α、IL-4、IL-8相比其他组,含量明显增长(P 0. 05);肾组织中HMGB1、LC3及Beclin-1蛋白表达水平显著高于其他各组(P 0. 05),肾明显充血,与周围结缔组织黏连不可分,细胞形态不规则,细胞表面微绒毛显著减少,胞核变形,染色质边集。与模型对照组相比,真武汤治疗组及阳性对照组大鼠肾组织微观病理损伤明显减轻,外周血中TNF-α、IL-4、IL-8含量降低(P 0. 05);肾组织中HMGB1、LC3及Beclin-1蛋白表达水平显著降低(P 0. 05),且真武汤治疗组具有剂量依赖性(P 0. 01)。结论:真武汤可通过有效抑制肾病综合征模型大鼠子肾组织炎性因子表达,调节HMGB1/Beclin-1信号通路,对肾病综合征模型大鼠肾组织起到保护作用。     

血管生成抑制剂TNP-470对ACHN肾癌的抑制作用

目的　探讨血管生成抑制剂TNP 470抑制ACHN肾癌生长和转移的作用机制。方法　采用TNP 470 (4 0mg·kg-10 .2ml-1)皮下注射治疗ACHN肾癌荷瘤裸鼠 ,观察肿瘤生长情况。 3 1d后处死裸鼠 ,测定肿瘤体积 ;采用免疫组织化学方法和原位缺口末端标记 (TUNEL) ,观察TNP 470对肺转移、肿瘤微血管密度 (MVD)、肿瘤细胞增殖指数 (PI)和凋亡指数 (AI)的影响。结果　治疗组生长明显减慢 [重量 (2 70 .0 0± 62 .3 5 )mgvs (63 0 .0 0± 12 3 .65 )mg ;体积 (12 6.5 4±45 .12 )mm3 vs (3 16.16± 60 .2 8)mm3 ,P <0 .0 1] ,MVD明显减少 (5 .65± 2 .3 1vs 12 .0 0± 3 .78,P <0 .0 1) ,AI明显增加 (5 .0 8± 1.87vs 1.75± 0 .83 ,P <0 .0 1)。MVD与AI呈负相关 ,与肿瘤体积呈正相关 ,相关系数分别为r =-0 .860 7,P <0 .0 1;r =0 .714 4,P <0 .0 1。AI与肿瘤体积呈负相关 (r =-0 .85 40 ,P <0 .0 5 )。结论　TNP 470对ACHN肾癌有显著的抗血管生成的作用 ,对肿瘤的生长和转移有明显的抑制作用 ,其机制可能为抑制肿瘤血管生成使之缺血缺氧 ,从而引起肿瘤细胞凋亡增加     

19-去甲睾酮对性腺发育不良小鼠附性腺生长的影响

目的 :观察合成同化甾体激素 19 去甲睾酮 (NT)对性腺发育不良 (hpg)小鼠的前列腺、精囊腺 (SV)、附睾生长发育的影响 ,为用药的安全性提供实验依据。　方法 :NT硅胶囊皮下埋植 5周缓释给药 ,设给药hpg小鼠实验组 (n =7)、不给药hpg小鼠对照组 (n =7)和性腺发育正常小鼠对照组 (n =10 )。给药结束后测定前列腺腹侧叶(VP)、SV和附睾的重量及VP腺管末梢数目。　结果 :与hpg小鼠对照组相比 ,hpg小鼠给药组各附性腺的重量均显著增加 (P <0 .0 0 5 ) ,VP腺管分支形态发育趋于正常 ;hpg小鼠给药组SV的重量与正常小鼠相同 ,但VP、附睾的重量及VP腺管末梢数目仍显著低于正常性腺小鼠对照组 (P <0 .0 0 5 )。　结论 :NT能明显刺激hpg小鼠附性腺的生长发育     

丹参对大鼠内毒素休克性肺损伤的保护作用

目的　探讨丹参对内毒素休克性肺损伤的防治作用。方法　选用SD大鼠 5 4只 ,随机分成对照组、肺损伤组和丹参防治组。三组动物根据注入内毒素后时间不同分为 1、2和 4小时三小组。丹参防治组按 8g/kg体重经颈静脉注入丹参 ,30分钟后 ,再按 5mg/kg体重经颈静脉注入大肠杆菌内毒素 ;肺损伤组以生理盐水代替丹参 ;对照组中 ,丹参和内毒素均以等量生理盐水代替。实验结束后 ,取血和肺组织行血浆P 选择素、肺组织MPO活性、肺毛细血管通透性和血液流变学检测。结果　 (1)肺损伤组各时相点血浆P 选择素、肺组织MPO活性、肺毛细血管通透性均较对照组显著增高 (P <0 0 1) ;丹参防治组较肺损伤组有所下降 ,以 4小时为甚 (P <0 0 1)。 (2 )肺损伤组血液流变学指标较对照组明显升高 (P <0 0 1) ;丹参防治组与肺损伤组比较 ,血液流变学指标有不同程度的降低 ,以高中切变率 ηb和ERI差异有显著 (P <0 0 5或P <0 0 1)。 结论　丹参通过改善血液流变性 ,抑制P 选择素介导的PMN的浸润发挥对肺损伤的保护作用     

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.     

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.