不同浓度铁离子对成骨细胞铁离子通道蛋白的影响

目的 铁过载与骨代谢相关,在人成骨细胞(hFOB1.19)中,膜转铁蛋白(FPN1)、转铁蛋白受体(TfR)和二价金属转运蛋白1(DMT1)是细胞内铁离子进入和排除的重要通道蛋白;本研究用不同浓度铁离子干预成骨细胞培养,观察成骨细胞铁离子通道蛋白基因表达变化和相互联系,了解铁过载对相关通道蛋白的影响意义.方法人成骨细胞在34℃下进行体外培养,以不同浓度枸橼酸铁铵FAC(50 μmol/L、100 μmol/L、200 μmol/L)干预成骨细胞培养,48小时后收集细胞,按不同干预组抽提总RNA,采用半定量RT-PCR法检测成骨细胞中TfR、DMT1、FPN1 mRNA的表达.结果①RT-PCR检测显示不同浓度FAC干预成骨细胞后,各组FPN1、TfR、DMT1 mRNA均有表达;②不同浓度组FPN1、TfR、DMT1 mRNA表达光密度比值不同,组间密度比值比较存在统计学意义(P<0.05);③培养环境铁离子浓度增高可以使得FPN1的mRNA表达上调,而TfR、DMT1的mRNA表达下调.结论 成骨细胞的铁通道蛋白受环境铁离子影响,在一定范围内随着细胞外铁离子浓度增加,细胞膜铁离子进入通道功能下调、排除通道功能上调,说明铁过载对成骨细胞内铁离子水平有明显影响.     

克伦特罗及普萘洛尔对去势大鼠骨代谢的影响

目的 研究克伦特罗及普萘洛尔对去势大鼠骨代谢的影响.方法 48只2月龄雌性大鼠随机分为6组,其中3组切除卵巢,另外3组不切除.饲养3个月后,分别给予β2肾上腺素受体激动剂克伦特罗(Clenbuterol)及β肾上腺素受体阻滞剂普萘洛尔(Propranolol)腹腔注射3个月.使用骨密度测量仪测量其股骨及腰椎骨密度,酶联免疫吸附试验法检测大鼠体内血清骨钙素浓度.处死后取胫骨,分别进行脱钙HE染色后观察.结果 未去势大鼠股骨及腰椎的骨密度分别是0.230±0.011g/cm2及0.226±0.009 g/cm2,OVA组大鼠股骨及腰椎的骨密度分别是0.201±0.010 g/cm2及0.201±0.011 g/cm2,OVA+Clen组大鼠的股骨及腰椎骨密度分别为0.187±0.012 g/cm2及0.189±0.013g/cm2,OVA+Pro组大鼠的股骨及腰椎骨密度分别为0.213±0.009 g/cm2及0.213±0.008 g/cm2;未去势组大鼠骨钙素浓度为2.941±0.066μg/L,OVA组大鼠骨钙素浓度为4.162±0.080μg/L,OVA+Clen组大鼠骨钙素浓度为3.973±0.088μg/L,OVA+Pro组大鼠骨钙素浓度为4.255±0.058μg/L.结论 克伦特罗能显著降低去势大鼠股骨骨密度;增加血清骨钙素的浓度.普萘洛尔能增加去势大鼠腰椎及股骨的骨密度,降低血清骨钙素的浓度.     

铁代谢相关蛋白在烧伤后增生性瘢痕中的表达

目的:探讨烧伤后增生性瘢痕患者中铁代谢相关蛋白的表达情况。方法:组织标本均来自2016年-2018年石家庄市第一医院烧伤整形外科住院患者。患者分三组:正常皮肤组、萎缩性瘢痕组、增生性瘢痕组。后两组患者分别采集瘢痕及其自身正常皮肤标本。术中采集标本,应用电感耦合质谱分析仪测定三组标本中组织铁含量。免疫组织化学染色检测增生性瘢痕中铁代谢相关蛋白转铁蛋白受体1 (transferrin receptor 1,TfR1)、铁蛋白(ferritin,FTL)、二价金属离子转运蛋白1(divalent metal transporter 1,DMT1)、膜铁转运蛋白1(ferroportin 1,FPN1)等在增生性瘢痕中的表达。结果:三组正常皮肤组织中组织铁含量比较差异无统计学差异(P0.05)。增生性瘢痕组:增生性瘢痕组织比自身正常皮肤组织中组织铁含量升高,差异有统计学意义(P0.05)。免疫组化显示增生性瘢痕组中增生性瘢痕组织及自身正常皮肤组织中均有铁代谢相关蛋白的表达,多表达于胞浆中,在表皮层表达较强。其中DMT1(±IRE)、FPN1以及FTL在增生性瘢痕组织中表达量高于其自身正常皮肤组织(P0.05);TfR1在增生性瘢痕组织中表达量却降低(P0.05)。结论:增生性瘢痕组患者瘢痕局部铁元素沉积过多,进而细胞内可能通过IRP/IRE系统调节铁的摄取和释放,而且推测主要依赖于TfR1以及FPN1的作用而非DMT1(±IRE)。     

肝硬化脾功能亢进患者肝组织中铁过载及铁调素mRNA表达的意义

目的 探讨肝硬化合并不同程度脾功能亢进(脾亢)患者肝组织中铁过载及铁调素(hepcidin)mRNA表达的意义.方法 收集肝硬化合并轻、中及重度脾亢患者肝活检标本各10例,共30例(肝硬化组),外伤性肝破裂手术标本10例(对照组),采用原子分光光度计检测肝组织铁元素含量;采用化学发光法检测血清铁蛋白的含量;采用逆转录-聚合酶链反应(RT-PCR)检测肝组织hepcidin mRNA的表达.结果 肝硬化脾亢患者按脾功能亢进程度分为轻、中及重度3组,其肝组织中铁元素含量明显递增,分别为(0.1205±0.0021)、(0.1624±0.0028)和(0.1716±0.0032)mmol/g,均明显高于正常肝组织(0.0639±0.0025)mol/g(P<0.05),表现为铁过载;肝硬化组血清铁蛋白的含量为(436.2±51.6)μg/L,显著高于对照组的(152.5±38.7) μg/L(P<0.01);肝硬化组hepcidin mRNA的表达水平为1.73±0.26,明显高于对照组的0.68±0.22(P<0.01);而且各组的hepcidin mRNA表达水平与血清铁蛋白含量之间具有显著相关性(肝硬化组r=0.735,对照组r=0.648,P<0.01).结论 肝硬化脾亢患者的肝组织中存存铁过载,并随脾亢程度加重而明显增加;hepcidinmRNA是调节铁代谢平衡并影响肝硬化进程的重要因素.     

下丘脑促肾上腺皮质激素释放因子受体2反义寡核苷酸在严重烧伤大鼠高代谢反应中的作用

目的 了解下丘脑促肾上腺皮质激素释放因子受体2(CRFR2)反义寡核苷酸(ASP)在严重烧伤大鼠高代谢反应中的作用. 方法 将36只SD大鼠大脑立体定位、第三脑室置管.其中30只烧伤后,根据脑室注人物的不同,分为烧伤对照组(注入等渗盐水3μL)、CRFRI正义寡核苷酸(ODN)组(注入CRFRlODN 10 μg)、CRFRIASP组(注入CRFR1ASP 10 μg)、CRFR20DN组(注入CRFR20DN 10 μg)、CRFR2 ASP组(注入CRFR2 ASO 10 μg).每组6只大鼠.另取6只大鼠作为正常对照组,不致伤,仅在脑室内注入等渗盐水3μL.分别于伤后5、6 d在大鼠清醒状态下经脑室置管注射药物.伤后7 d经该管注入20 g/L甲紫3μL,当日检测大鼠静息能量消耗(REE),并取大鼠脑组织检测CRFR2 mRNA表达及CRFR2蛋白含量. 结果 烧伤对照组、CRFR10DN组、CRFR1ASO组、CRFR20DN组、CRFR2ASO组REE值分别为(11 840±987)、(11 133±1100)、(10 733±1338)、(11 123±1321)、(7563±890)kJ·(m2)-1·d-1,均高于正常对照组[(6641±526)kJ-(m2)-1·d-1,P＜0.05],而CRFR2ASO组却明显低于CRFR20DN组(P＜0.01).烧伤对照组伤后脑组织CRFR2 mRNA的表达和CRFR2蛋白含量明显增加,而CRFR2ASO组CRFR2 mRNA表达及CRFR2蛋白含量却低于正常对照组(P＜0.01). 结论 中枢应用CRFR2ASO可下调下丘脑CRFR2 mRNA表达和蛋白含量,降低烧伤高代谢反应,下丘脑CRFR2受体可介导大鼠烧伤后高代谢反应.     

去势大鼠股骨组织中Wntl0b的表达

目的观测去势大鼠骨质疏松模型中股骨组织Wnt10b的表达。方法 20只SD雌性大鼠随机分为去势组和对照组两组。大鼠切除双侧卵巢去势诱发骨质疏松症。术后3个月腹主静脉取血,用放射免疫法测定各组大鼠血清E2水平。从股骨中提取总RNA和蛋白,分别采用RT-PCR和免疫印迹的方法检测Wnt10b在mRNA和蛋白表达水平上的变化。结果去势组大鼠血清E2含量为10.228±4.094 pmol/L;对照组血清E2含量为21.975±3.021 pmol/L。经RT-PCR和免疫印迹检测发现,与对照组相比,去势大鼠Wnt10b的mRNA和蛋白水平表达量均降低。结论去势大鼠骨质疏松模型体内股骨组织中Wnt10b的mRNA和蛋白表达水平均下降,以上结果提示Wnt10b可能在大鼠去势诱发骨质疏松模型中通过调节成骨等过程参与了骨质疏松的发展过程。     

BMMSCs对SD大鼠DCD供肝常温机械灌注脂肪变性的影响机制研究

目的研究铁死亡在骨髓间充质干细胞(BMMSCs)联合常温机械灌注(NMP)修复SD大鼠心脏死亡器官捐献(DCD)脂肪变性供肝中的作用。方法提取SD大鼠BMMSCs。建立大鼠脂肪肝DCD模型。24只SD大鼠随机分为单纯脂肪肝组(Sham)、静态冷保存组(SCS)、常温机械灌注保存组(NMP)、BMMSCs联合NMP保存组(BNMP), 不同条件下保存DCD脂肪供肝4 h。通过检测肝脏病理、灌注液肝脏酶学和乳酸含量、胆汁分泌量和炎症因子指标, 对肝脏进行功能质量评估;检测肝组织中Fe2+、丙二醛和还原型谷胱甘肽(GSH)含量, 以及肝脏中环氧合酶-2、前列腺素内过氧化物合酶2(Ptgs2)、谷胱甘肽过氧化物酶4(GPX4)及铁蛋白重链1(FTH1)的mRNA或蛋白表达, 评价肝脏铁死亡发生。结果 BNMP和NMP组的肝脏病理、促炎及抗炎细胞因子的表达均优于SCS组;机械灌注保存期间, BNMP组丙氨酸氨基转移酶、天冬氨酸氨基转移酶和乳酸含量均低于NMP组[灌注4 h:(189.0±12.5)U/L比(227.7±16.2)U/L、(207.3±18.6)U/L比(247.0±11.8)U/...     

铁调素在大鼠慢性移植肾肾病中的表达及其意义

目的 探讨铁调素(Hepcidin)在大鼠慢性移植肾肾病(CAN)动物模型中的表达变化及临床意义.方法 以F344近交系大鼠为供体、Lewis近交系大鼠为受体,原位肾移植,建立20只CAN大鼠模型;于模型建立术前、术后1、2及4个月分别收集大鼠的静脉血和尿样,检测肾功能;酶联免疫吸附法(ELISA)检测血清、尿Hepcidin、血清白细胞介素-6(IL-6)和促红细胞生成素(EPO)的表达;并于移植后2个月及4个月分别处死大鼠10只,观察各组大鼠移植肾组织病理学变化.结果 血清Hepcidin、IL-6表达随着移植术的时间逐渐增高,术前、术后1、2及4个月分别为(8.18±1.60)、(10.94±2.10)、(12.71 ±2.10)、(15.81±2.40) μg/L; (2.52±0.41)、(15.58 ±6.94)、(18.16±7.08)、(25.71 ±5.71) ng/L.尿Hepcidin排出逐渐减少,术前、术后l、2及4个月分别为(17.52±2.60)、(13.65 ±2.80)、(12.02±1.30)、(10.13 ±1.80) μg/L,EPO表达逐渐减少术前、术后1、2及4个月分别为(15.51 ±0.76)、(10.29 ±0.58)、(6.37 ±0.82)、(1.23±0.15) U/L,术前与术后比较差异有统计学意义(P＜0.05);移植术后大鼠血肌酐(Cr)、尿素氮(BUN)逐渐升高,并且Cr与血清Hepcidin呈正相关;移植术后血清Hepcidin的表达与IL-6呈正相关,与EPO呈负相关;肾脏病理形态、HE染色符合CAN的病理改变.结论 随着移植肾功能的减退,大鼠体内微炎性反应增加,Hepcidin在大鼠CAN模型表达变化与肾功能有关.Hepcidin随着时间和炎症状态表达的变化可反映肾功能损伤.     

环孢素A在透明质酸诱导大鼠间质性膀胱炎/膀胱疼痛综合征中的治疗作用

目的观察环孢素A(Cs A)在透明质酸酶诱导的大鼠间质性膀胱炎/膀胱疼痛综合征(IC/BPS)中的治疗作用。方法将45只成年雌性Sprague-Dawley(SD)大鼠(200~250 g),分为对照组15只(膀胱灌注生理盐水),模型组15只(膀胱灌注透明质酸酶),Cs A治疗组15只(膀胱灌注透明质酸酶+Cs A)。采用长期(1个月)间歇灌注透明质酸酶(4 g/L)构建大鼠IC/BPS模型,尿流动力学检测膀胱功能,Von Frey刷检测泌尿生殖区疼痛变化,硝酸还原酶法测定膀胱组织NO的含量,逆转录聚合酶链反应(RT-PCR)检测i NOS、IL-6、IL-10及IL-17 m RNA表达,ELISA法检测膀胱组织IL-6、IL-10及IL-17含量。结果与对照组相比,模型组膀胱大鼠膀胱i NOS、IL-6、IL-10、IL-17 m RNA表达均显著升高(P0.001),在予以Cs A治疗后,其m RNA表达均显著下调(P0.05)。模型组膀胱NO含量为9.73±2.62μmol/g;IL-6含量为125.4±11.25μg/g;IL-10含量为64.05±6.26μg/g;IL-17含量为90.61±10.49μg/g;排尿时间间隔为148.23±40.75 s;膀胱容量为0.41±0.06 m L。对照组膀胱NO含量为1.31±0.55μmol/g;IL-6含量为55.18±5.07μg/g;IL-10含量为32.12±3.82μg/g;IL-17含量为44.45±4.92μg/g;排尿时间间隔为441.90±34.96 s;膀胱容量为1.27±0.10 m L。与对照组比较,模型组大鼠膀胱NO、IL-6、IL-10、IL-17含量均明显升高,排尿时间间隔缩短,膀胱容量降低,疼痛评分显著增加(P0.05)。与模型组相比,Cs A治疗组大鼠的膀胱组织NO、IL-6、IL-10、IL-17含量均显著减少(P0.001),分别为3.97±1.71μmol/g;62.29±6.68μg/g;33.51±5.77μg/g;51.88±6.67μg/g,排尿时间间隔及膀胱容量明显增加(P0.05),分别为422.06±42.22 s、1.14±0.15 m L,疼痛评分也明显下调(P0.05)。结论在透明质酸酶诱导的IC/BPS大鼠模型中,Cs A膀胱灌注治疗能显著改善大鼠的尿流动力学及疼痛症状,这可能与其下调i NOS、NO、IL-6、IL-10及IL-17等炎症介质的表达有关。     

血红素加氧酶2和CO在去势大鼠阴茎海绵体中的表达

目的:检测去势大鼠阴茎海绵体中血红素加氧酶2(HO-2)/CO的表达,初步探讨勃起功能障碍(ED)的发病机制。方法:雄性SD大鼠72只均分为对照组、假手术组、去势组和去势锌原卟啉(Zn PP,HO阻断剂)组,检测基础条件和阿扑吗啡(APO)刺激后的海绵体内压(ICP)和勃起率;激光共聚焦显微镜检测大鼠勃起不同时期阴茎海绵体组织中HO-2蛋白的表达,分光光度计测定CO在大鼠勃起不同时期的含量。结果:基础条件和APO刺激后ICP和勃起率,去势组[(11.68±0.69)mm Hg,(54.81±3.86)mm Hg,33.3%]和去势Zn PP组[(11.20±0.71)mm Hg,(41.17±5.41)mm Hg,22.2%],与对照组[(22.83±2.66)mm Hg,(66.92±7.77)mm Hg,100%]和假手术组[(23.35±2.22)mm Hg,(70.43±7.22)mm Hg,100%]比较显著下降(P均0.01),且APO刺激后去势Zn PP组ICP较去势组明显降低(P0.01)。APO刺激后,勃起前和勃起中阴茎海绵体HO-2蛋白表达,去势组(445.4±23.7,847.4±35.0)和去势Zn PP组(390.1±29.7,526.0±52.5)较对照组(512.7±57.4,1 145.2±89.8)和假手术组(583.7±8.0,1 016.3±79.8)显著下降(P0.05或P0.01),且勃起中去势Zn PP组HO-2蛋白表达较去势组明显降低(P0.01);勃起后各组之间的HO-2蛋白表达变化差异无显著性。勃起前、中和后阴茎海绵体CO含量,去势组[(20.59±1.01)×10-7nmol/L,(32.53±1.26)×10-7nmol/L,(18.71±1.22)×10-7nmol/L]和去势Zn PP组[(12.52±1.05)×10-7nmol/L,(21.90±1.02)×10-7nmol/L,(16.56±0.55)×10-7nmol/L]较对照组[(26.76±1.41)×10-7nmol/L,(48.25±1.01)×10-7nmol/L,(27.10±1.58)×10-7nmol/L]和假手术组[(25.41±2.09)×10-7nmol/L,(47.90±1.22)×10-7nmol/L,(25.67±1.20)×10-7nmol/L]显著下降(P0.05或P0.01),且勃起中去势Zn PP组CO含量较去势组明显下降(P0.01)。结论:HO-2和CO表达下降与去势大鼠ED的发生有关。     

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.