β-内酰胺类抗生素在胆汁中的浓度和药动学的实验研究

目的 研究β-内酰胺类抗生素在胆汁中的浓度及其药动学,并对杀菌效力进行评估,为临床上肝胆系统感染选择用药提供参考和依据.方法 家兔行胆总管造瘘术,分别静脉注射哌拉西林/他唑巴坦、头孢曲松和美罗堵南等β-内酰胺类抗生素后于不同时间收集胆汁标本,采用HPLC法测定各抗生素的浓度,并计算出药动学参数.结合最低抑菌浓度(MIC),评估抗生素在胆汁中的杀菌效力.结果 各抗生素在胆汁中的峰浓度和半衰期分别为:哌拉西林(7950.16±3023.00)μg/ml和(1.97±1.23)h,头孢曲松(1107.01±247.61)μg/ml和(3.14±0.57)h,美罗培南(31.97±12.44)μg/ml和(0.36±0.11)h.哌拉西林/他唑巴坦的杀菌指数最大、TMIC最长,对大部分胆道感染常见致病菌均可形成MIC90 100倍以上的浓度,TMIC长达6～8 h;头孢曲松和美罗培南较低.结论 哌拉西林、头孢曲松和美罗培南均可在胆汁中达到有效杀菌浓度,哌拉西林/他唑巴坦杀菌效力最强.     

抗菌药物在胆汁中药物代谢动力学特点的实验研究及杀菌效力评价

目的 探讨6种抗菌药物在胆汁中的药物代谢动力学特点,并评估其杀菌效力.方法 实验用健康家兔36只,随机分为6组,每组6只.行胆总管造瘘术后,分别静脉注射头孢曲松、头孢哌酮/舒巴坦钠、哌拉西林/他唑巴坦、美罗培南、左氧氟沙星、甲硝唑,于注射后不同时间收集家兔胆汁标本,采用高效液相色谱法测定各抗菌药物的浓度,并计算出药物代谢动力学参数.结合最低抑菌浓度(MIC)评估各抗菌药物在胆汁中的杀菌效力.结果 各抗菌药物在胆汁中的峰浓度和半衰期分别为:哌拉西林(7 950 ±3 023) mg/L和(1.97±1.23)h,头孢曲松(1 104±248) mg/L和(3.14±0.57)h,头孢哌酮(5 215 ±2 225) mg/L和(0.89 ±0.13)h,美罗培南(31.97 ±12.44) mg/L和(0.36±0.11)h,左氧氟沙星(66.3±36.9) mg/L和(3.32±2.57)h,甲硝唑(28.2±10.2) mg/L和(0.81 ±0.33)h.哌拉西林/他唑巴坦和头孢哌酮/舒巴坦的杀菌指数最大,分别为(62.1±23.6) ～(993.8±377.9)和(164.8 ±69.0) ～ (659.3 ±275.9),其药物浓度持续在MIC以上的时间(T＞MIC)最长,两药的T＞MIC分别为(6.00±2.53)～(8.00±0.00)h和(6.33±1.97) ～ (8.00±0.00)h;左氧氟沙星的杀菌指数[(2.1±1.2)～(8.3±4.6)]和T＞MIC[(0.54±0.25)～(2.67±1.03)h]最小,头孢曲松和美罗培南居中,其杀菌指数和T＞MIC分别为(4.3±1.0) ～ (69.2±15.5)、(1.42±0.65)～(8.00±0.00)h和(2.0±0.8)～(1 031.3 ±401.4)、(0.29 ±0.10) ～ (1.83 ±0.26)h.甲硝唑对厌氧菌的杀菌指数和T＞MIC分别为7.4 ～294.9和1.88 ～5.00 h.结论 6种抗菌药物均可在胆汁中达到有效杀菌浓度,哌拉西林、头孢哌酮、美罗培南、甲硝唑在家兔胆汁中呈一房室模型,头孢曲松、左氧氟沙星为二房室模型分布.哌拉西林/他唑巴坦和头孢哌酮/舒巴坦杀菌效力最强,甲硝唑对厌氧菌有较强的杀菌力,肝胆系统感染应结合临床选用杀菌效力强的抗菌药物.     

Wilson''''s病患者亲体部分肝移植和全肝移植术后血清铜蓝蛋白及尿铜水平的变化

目的　总结Wilson’s病患者亲体肝移植和全肝移植术后血清铜蓝蛋白及尿铜水平的恢复情况。方法　自 2 0 0 0年 9月至 2 0 0 3年 11月我院为 2 6例Wilson’s病患者施行了肝移植术 ,均并发终末期肝硬变 ,其中 3例发生急性肝功能衰竭。术前血清铜蓝蛋白和尿铜水平分别为 (12 4 .8± 2 2 .8)mg/L和 (15 2 4 .8± 32 8.6 ) μg/ 2 4h ,其中行活体部分肝移植 2 2例 ,全肝移植 4例 ,亲体肝移植供体术前血清铜蓝蛋白水平为 (2 30 .4± 2 9.6 )mg/L ,尿铜水平均 <5 0μg/ 2 4h。结果　所有患者手术顺利 ,全肝移植患者术后 1、3、6及 12个月血清铜蓝蛋白和尿铜水平分别为 (32 0 .2±36 .8)mg/L、(380 .4± 4 5 .6 )mg/L、(36 0 .5± 37.6 )mg/L、(35 6 .2± 2 7.6 )mg/L和 (2 4 0 .4± 2 2 .8) μg/ 2 4h、(86 .5± 10 .6 ) μg/ 2 4h、(5 4 .2± 6 .8) μg/ 2 4h及 (46 .8± 3.4 ) μg/ 2 4h ;亲体肝移植患者术后 1、3、6及 12个月血清铜蓝蛋白和尿铜水平分别为 (2 16 .8± 2 0 .4 )mg/L、(2 4 8.5± 32 .6 )mg/L、(2 85 .4± 4 4 .3)mg/L、(2 6 0 .2± 36 .6 )mg/L和(380 .8± 37.6 ) μg/ 2 4h、(15 0 .6± 2 4 .5 ) μg/ 2 4h、(75 .5± 9.6 ) μg/ 2 4h及 (6 0 .3± 5 .8) μg/ 2 4h。结论　全肝移植和亲体肝     

硬膜外腔罗比卡因的浓度及容量对镇痛效果的影响

目的　观察不同浓度、不同速率罗比卡因在开胸术后硬膜外腔的镇痛效果及不良反应。方法　 6 0例开胸手术后病人随机均分为四组 :Ⅰ组 ,0 0 5 %罗比卡因 +芬太尼 1μg/ml,8ml/h ;Ⅱ组 ,0 1%罗比卡因 +芬太尼 2 μg/ml,4ml/h ;Ⅲ组 ,0 2 %罗比卡因 +芬太尼 4 μg/ml,2ml/h ;Ⅳ组 ,0 1%布比卡因 +芬太尼 2 μg/ml,4ml/h。各组病人硬膜外自控镇痛 (PCEA)每次 2ml,锁定时间15min。各组负荷量为芬太尼 5 0 μg +0 75 %罗比卡因或布比卡因 (2ml) +生理盐水至 4ml。观察病人静息和咳嗽疼痛评分及不良反应。结果　镇痛效果及术后 4 8h疼痛评分 ,Ⅰ、Ⅱ、Ⅳ组之间无明显差异 (P >0 0 5 ) ,但明显优于Ⅲ组 (P <0 0 5 ) ,且 4 8hPCEA消耗量、总按压次数与有效按压次数之比 (TPCA/EPCA)Ⅲ组明显高于Ⅰ、Ⅱ、Ⅳ组 (P <0 0 5 )。Ⅲ组术后当日还需辅助使用其他镇痛药(5 / 15 )。瘙痒、恶心、呕吐、镇静程度各组之间差异无显著性。均未观察到呼吸抑制或下肢运动神经阻滞。Ⅳ组出现血压下降 6例 (4 0 % ) ,自觉咳嗽无力 3例 (2 0 % ) ,Ⅲ组自觉咳嗽无力 2例 (13 33% )。结论　 0 0 5 %罗比卡因 +芬太尼 1μg/ml、背景 8ml/h或 0 1%罗比卡因 +芬太尼 2 μg/ml、背景 4ml/h对开胸手术后病人不仅有良好的镇痛效果 ,     

生长抑素减轻大鼠急性坏死性胰腺炎的肠屏障损害

目的　观察生长抑素对大鼠急性坏死性胰腺炎 (ANP)肠屏障损害和肠道内毒素移位的影响。方法　采用胰管逆行灌注法复制大鼠ANP模型 ,随机分为正常对照组 (n =6 )、假手术组(n =18)、ANP组 (n =2 0 )和生长抑素治疗组 (n =19)。观察胰腺病理、血淀粉酶、肿瘤坏死因子(TNFα)和白细胞介素 (IL) 1β、肠上皮细胞间紧密连接、肠通透性 (血浆D 乳酸 )、循环内毒素和病死率的变化。结果　生长抑素减轻了ANP早期胰腺病理改变〔8h组织学评分由 (4 2± 0 3)降至 (2 0±0 4) ,P <0 0 1〕 ;72h血淀粉酶由 (6 2 31± 44 6 1)U/L降至 (2 6 48± 1798)U/L ,P <0 0 5 ;72hTNFα由(4 7± 2 4)pg/ml降至 (2 3± 2 1)pg/ml,IL 1β由 (10 3± 40 )pg/ml降至 (5 0± 2 4)pg/ml,P均 <0 0 5 ;肠上皮细胞间紧密连接的破坏减轻 ;2 4h血浆D 乳酸由 (14 7± 4 9) μg/ml降至 (8 0± 4 2 ) μg/ml,P <0 0 1;2 4h血浆内毒素由 (0 6 11± 0 2 10 )EU/ml降至 (0 336± 0 110 )EU/ml,P <0 0 1;ANP大鼠 72h病死率由 5 9%降至 17% ,P <0 0 5。结论　生长抑素可减轻ANP大鼠的肠屏障损害 ,对肠道内毒素移位有抑制作用 ,可降低ANP大鼠的病死率。     

胆汁泡蛋白ELISA检测法的ROC曲线分析

目的　评价用ELISAkit检测胆固醇性胆结石的准确性。方法　构建胆汁 335 0 0泡蛋白检测试剂盒 ,测定正常人、胆固醇性结石症、胆色素性结石症患者胆囊胆汁泡蛋白含量 ,用受试者工作特征 (receiveroperatingcharacteristic ,ROC)曲线分析评价不同截割点含量的试剂盒诊断价值。结果　胆固醇性结石组、胆色素性结石组和正常人群组胆囊胆汁 335 0 0泡蛋白含量依次为 (2 13± 70 ) μg/ml、(72± 5 5 ) μg/ml及 (6 5± 5 2 ) μg/ml,其中胆固醇性结石组泡蛋白含量明显高于胆色素性结石组和正常人群组 (F =6 0 9,P <0 0 5 ) ;当泡蛋白截割点含量为 14 3μg/ml时 ,该ELISAkit诊断胆固醇性胆石症的敏感度、特异度和符合率分别为 85 %、90 %和 88% ,ROC曲线下面积值高达 0 96。结论　不同人群存在胆汁泡蛋白含量分布的异质性 ,ELISAkit辅助诊断胆固醇性胆结石具有潜在的临床应用价值。     

胆囊结石及癌变过程中肿瘤坏死因子可溶性受体的变化

目的　探讨可容性肿瘤坏死因子受体 (sTNFR)在胆囊结石及癌变过程中的变化。方法　用双抗体夹心酶联免疫法对 5 3例胆囊结石 ,9例胆囊癌及 11例正常对照者血清及胆法中的sTNFR水平进行检测。结果　血清及胆汁中sTNFR水平胆囊癌组为 (2 .63± 0 .5 6) μg/L、(10 .0 2± 3 .2 3 ) μg/L较胆石症组 (1.2 5± 0 .3 6) μg/L、(2 .81± 0 .93 ) μg/L及对照组 (0 .95± 0 .19)μg/L、(1.83± 0 .5 4) μg/L均显著升高 (P <0 .0 1)。胆囊黏膜从典型增生、非典型增生到胆囊癌的发展过程中sTNFR在血清 (1.11± 0 .2 8、1.5 3± 0 .3 2、2 .63± 0 .5 6)及胆汁中 (2 .5 0± 0 .81、3 .42±0 .87、10 .0 2± 3 .2 3 )逐级增高 (各组间P <0 .0 5 )。胆汁中sTNFR水平在胆囊癌Ⅰ～Ⅲ期 (8.3 6±2 .60 )与Ⅳ～Ⅴ期 (13 .3 3± 4.46)间差异有显著性 (P <0 .0 0 1) ,肿瘤直径≥ 2cm组 (12 .10± 2 .3 2 )与 <2cm组 (7.42± 2 .10 )间差异有显著性 (P <0 .0 5 )。胆汁中TNFR水平明显高于其对应的血清水平 ,两者之间呈正直线相关 (r =0 .875 ,P <0 .0 0 1)。胆囊癌术后血清sTNFR水平显著下降。结论　sTNFR参与胆囊结石致癌的过程 ,与胆囊癌的临床生物学特点密切相关。     

肾移植受者应用他克莫司治疗窗浓度的探讨

目的　寻求适合国人肾移植受者他克莫司 (FK5 0 6 )理想治疗窗浓度范围。方法　应用微粒子酶免疫分析法测定 5 8例肾移植患者口服FK5 0 6后 12h的血药谷浓度 ,并观察排斥反应的发生及药物的肾毒性。结果　FK5 0 6的血药浓度 ,术后 1个月为 (13.0± 2 .1) μg/L ,2～ 3个月为 (9.4±1.6 ) μg/L ,3个月以后为 (6 .5± 1.3) μg/L ,比较各时期全血FK5 0 6谷浓度 ,差异均有极显著性 (P <0 .0 1) ;术后发生急性排斥反应 3例次 ,肾毒性 4例次。结论　FK5 0 6具有良好的免疫抑制效果 ,其治疗窗浓度范围 ,术后第 1个月为 11～ 15 μg/L ,第 2～ 3个月为 8～ 11μg/L ;第 3个月后为 5～ 8μg/L ,此浓度范围既能达到满意的免疫抑制效果 ,又能减少FK5 0 6的肾毒性     

丙酮酸乙酯对重症急性胰腺炎大鼠血清高迁移率蛋白-1水平的影响及意义

目的　探讨重症急性胰腺炎 (SAP)大鼠血清高迁移率蛋白 1(HMGB1)水平的变化规律 ,以及丙酮酸乙酯 (EP)对其水平的影响和意义。方法　采用胰管逆行灌注人工胆汁的方法复制大鼠SAP模型。随机分为正常对照组 (N组 ,n =8)、重症急性胰腺炎组 (SAP组 ,n =80 )、EP治疗组 (Treat组 ,n =3 2 )。Treat组建模 12h开始使用EP治疗。酶联免疫吸附试验检测各组动物血清肿瘤坏死因子 α(TNF α)、白细胞介素 1β(IL 1β)水平。Westernblot法检测血清HMGB1水平。另设实验组研究EP对SAP大鼠生存时间的影响。结果　SAP组大鼠血清TNF α和IL 1β水平在建模 3～ 6h达高峰 ,12h即大幅下降。SAP组大鼠血清HMGB1水平在建模后 12h明显升高 ,至 2 4和 48h仍维持在较高水平 [(161.4± 2 2 .8) μg/L和(98.7± 15 .8) μg/L]。Treat组血清HMGB1水平在建模 2 4、48h [(95 .3± 3 0 .1) μg/L和(4 2 .2± 2 1.5 ) μg/L]明显低于SAP组(P <0 .0 5 )。而血清TNF α和IL 1β水平与SAP组比较差异无显著性。Kaplan Meier分析显示 ,EP治疗组动物生存时间 (71± 6)h明显高于SAP组 (4 6± 4)h (P <0 .0 0 0 1)。结论　HMGB1作为晚期炎症因子参与了SAP的全身炎症反应。延迟的EP治疗仍能降低SAP大鼠血清HMGB1水平 ,延长动物生存时间。     

南瓜蛋白对人胰腺癌SW1990细胞株的诱导凋亡作用

目的 探讨南瓜蛋白体外对人胰腺癌SW1990细胞株的诱导凋亡作用.方法 MTT法检测南瓜蛋白对SW1990细胞的增殖抑制作用,透射电镜观察细胞凋亡表现,流式细胞仪检测其凋亡率,Western blot法检测caspase-3蛋白的表达.结果 不同浓度(1.25、2.50、5.00、10.00、20.00、40.00及80.00 μg/ml)南瓜蛋白作用不同时间(24、48及72 h)后,南瓜蛋白对胰腺癌细胞具有生长抑制作用,并呈时间和剂量依赖性(P<0.05).40.00 μg/ml南瓜蛋白作用72 h后,透射电镜下可见细胞出现明显的凋亡改变,并可见凋亡小体;不同浓度(0、2.50、10.00、40.00μg/ml)南瓜蛋白作用72 h后,细胞的凋亡率分别为(0.30±0.11)%、(18.93±1.06)%、(28.00±2.07)%及(49.93±3.25)%,随着药物浓度的升高,细胞的凋亡率逐渐增加,呈浓度依赖性(P<0.05);caspase-3蛋白表达随着药物浓度的升高逐渐增强,呈浓度依赖性(P<0.05).结论 南瓜蛋白可能通过上调caspase-3蛋白的表达诱导胰腺癌细胞凋亡.     

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.     

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.     

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.