吗啡预处理对小鼠海马脑片氧-糖缺失/恢复时CaMKⅡ和NMDA受体的影响

目的 评价吗啡预处理对小鼠海马脑片氧-糖缺失，恢复时钙，钙调蛋白依赖性蛋白激酶Ⅱ（CaMKⅡ）膜转位及N-甲基-D-天冬氨酸（NMDA）受体磷酸化的影响。方法成年BALB／C小鼠，体重18-22g，雌雄不拘。每次将5只小鼠同批断头取脑，制备海马脑片，随机分为5组：正常对照组（Ⅰ组）、氧．糖缺失，恢复组（Ⅱ组）、吗啡预处理组（Ⅲ组）、纳络酮＋吗啡预处理组（Ⅳ组）及纳络酮预处理组（Ⅴ组）。Ⅰ组脑片正常体外培养，假操作换液。Ⅲ、Ⅳ、Ⅴ组小鼠海马脑片分别作相应预处理30min，间隔30min。Ⅱ、Ⅲ、Ⅳ、Ⅴ组建立小鼠海马脑片体外缺血再灌注损伤模型，分别氧-糖缺失20min，氧-糖恢复2h。各组于氧．糖缺失前即刻（T0）、氧-糖缺失20min（T1）、氧-糖恢复1h（T2）和2h（T3）取若干脑片匀浆、超声粉碎、离心，分离胞浆蛋白和膜相关蛋白；部分脑片分离总蛋白，Western blot检测CaMKⅡα蛋白表达量以及NMDA受体NR1亚单位的磷酸化。结果 海马脑片在T1、T2．T3时，CaMKⅡα膜相关蛋白含量增多。同时胞浆蛋白含量减少（P〈0．05）；T2、T3时，NMDA受体NR1亚单位磷酸化水平增高（P〈0．05）；而吗啡预处理明显地抑制上述CaMKⅡα膜转位及NMDA受体NR1亚单位磷酸化（P〈0．05）。纳络酮完全阻断吗啡预处理对CaMKⅡα膜转位及NR1磷酸化的抑制作用（P〈0．05）。CaMKⅡα总蛋白表达水平未见明显变化。结论 CaMKⅡ膜转位的抑制及NMDA受体磷酸化的抑制在吗啡预处理对小鼠海马脑片缺血再灌注的脑保护作用机制中起重要作用。     

硫化氢复合浅低温可选择性激活突触内NMDARs及其下游PI3K/Akt信号通路

目的观察硫化氢（H₂S）复合浅低温对大鼠全脑缺血-再灌注后海马N-甲基-D-天冬氨酸受体（NMDARs）的亚单位NR2A、NR2B、磷酸化蛋白激酶B（p-Akt）及磷酸化糖原合成酶激酶3β（p-GSK 3β）的影响,旨在探讨其发挥脑复苏作用的潜在机制。方法雄性SD大鼠100只,随机均分为五组:假手术组（Ⅰ组）、模型组（Ⅱ组）、浅低温组（Ⅲ组）、硫氢化钠（NaHS）组（Ⅳ组）、浅低温+NaHS组（Ⅴ组）。采用Pulsinelli-Brierley四血管阻塞法建立大鼠全脑缺血再灌注损伤模型,缺血15 min再灌注即刻Ⅳ组和Ⅴ组腹腔注射14μmol/kg NaHS,Ⅲ组和Ⅴ组行体表降温至肛温32～33℃。6 h后断头取海马,分别采用分光光度计法测H₂S的含量,western blot法测NR2A、NR2B、p-Akt及p-GSK 3β的表达,每组分别取4只于再灌注24 h取脑行Tunel染色观察CA1区锥体细胞凋亡情况。结果与Ⅰ组相比,Ⅱ、Ⅲ、Ⅳ、Ⅴ组海马组织H₂S含量均升高（P<0.05）;与Ⅱ组相比,Ⅳ和Ⅴ组H₂S含量显著升高（P<0.05）;与Ⅰ组相比,Ⅱ、Ⅲ、Ⅳ、Ⅴ组NR2A、NR2B的表达、凋亡指数（AI）均增高（P<0.05）,且Ⅱ和Ⅲ组NR2A/NR2B<1,Ⅰ、Ⅳ和Ⅴ组NR2A/NR2B>1;与Ⅰ组相比,Ⅱ、Ⅲ、Ⅳ、Ⅴ组海马p-Akt及p-GSK 3β的表达均上调（P<0.05）;与Ⅱ组相比,Ⅲ、Ⅳ、Ⅴ组海马p-Akt及p-GSK 3β的表达均上调,AI降低（P<0.05）;与Ⅲ和Ⅳ组相比,Ⅴ组海马p-GSK 3β的表达上调（P<0.05）。与Ⅱ组相比,Ⅲ、Ⅳ、Ⅴ组CA1区锥体细胞凋亡程度均明显减轻,尤以Ⅴ组效果最明显。结论 H₂S复合浅低温可能通过选择性作用于突触内的NMDARs,进而激活其下游促存活磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/Akt）信号通路,抑制锥体细胞凋亡,从而发挥脑复苏的作用。     

吗啡预处理减轻小鼠海马神经元氧-糖缺失/恢复损伤的影响因素

目的 探讨吗啡预处理减轻小鼠海马神经元氧-糖缺失/恢复损伤的影响因素(剂量和作用时间窗).方法 急性分离小鼠海马组织,制备脑片,行4部分实验,实验Ⅰ:应用吗啡0.1、0.3、0.5、1.0、3.0、10.0 μmol/L孵育脑片30 min,再常规培养30 min,缺氧无糖20 min,复氧复糖2 h.实验Ⅱ:应用吗啡3.0 μmol/L孵育脑片5、15、30、45、60 min,再常规培养30 min,缺氧无糖20 min,复氧复糖2 h.实验Ⅲ:应用吗啡3.0 μmol/L孵育脑片30 min,再常规培养即刻、5、15、30、60、120 min时行缺氧无糖20 min,复氧复糖2 h.实验Ⅳ:应用蛋白激酶C(PKC)非特异性抑制剂白屈菜赤碱10 μmol/L、选择性新奇型PKCε(nPKCε)抑制剂εVI.2 2 μmol/L、特异性钙-钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)抑制剂AIP 2 μmol/L、N.甲基-D-天冬氨酸(NMDA)受体特异性阻断剂MK-801 10 μmol/L孵育脑片30 min,再与吗啡3.0 μmol,L共同孵育30 min,常规培养30 min,缺氧无糖20 min,复氧复糖2 h.计算神经元存活率.结果 与氧-糖缺失/恢复组比较,吗啡0.5、1.0、3.0、10.0 μmol/L预处理组、吗啡预处理15、30、45、60 min组、吗啡预处理后常规培养即刻、5、15、30、60 min组神经元存活率升高(P<0.05).PKC、nPKGt、CaMKⅡ抑制剂和NMDA受体阻断剂可部分抑制吗啡预处理升高神经元存活率的作用.结论 有效减轻小鼠海马神经元氧-糖缺失,恢复损伤的吗啡预处理方式为:浓度0.5～1.0 μmol/L,持续时间15～60 min,间隔时间小于60 min;其保护作用可能部分依赖于PKC、nPKCε、CaMKⅡ的活化和NMDA受体的激活.     

YAP/OPA1信号通路在丙泊酚减轻小鼠海马神经元氧糖剥夺-复氧复糖损伤中的作用

目的评价Yes相关蛋白(YAP)/视神经萎缩蛋白1(OPA1)信号通路在丙泊酚减轻小鼠海马神经元氧糖剥夺-复氧复糖损伤中的作用。方法取正常培养处于对数生长期的HT22小鼠海马神经元, 采用随机数字表法分为4组(n=54):对照组(C组)、氧糖剥夺-复氧复糖组(OGD/R组)、丙泊酚组(P组)和丙泊酚+YAP沉默组(P+ siRNA-YAP组)。采用无糖无氧孵育6 h、复氧复糖培养24 h的方法制备神经元氧糖剥夺-复氧复糖损伤模型。P组于复氧复糖即刻加入丙泊酚终浓度50 μmol/L。P+ siRNA-YAP组于模型制备前48 h转染siRNA-YAP。采用CCK-8法检测神经元活力, 采用流式细胞术检测ROS含量和凋亡率, 采用分光光度法检测MDA含量、SOD活性以及线粒体膜电位(MMP), 采用荧光素荧光酶发光法检测线粒体ATP含量, 采用免疫荧光法观察YAP核转位, Western blot法检测YAP、磷酸化YAP(p-YAP)以及OPA1的表达。结果与C组比较, OGD/R组神经元活力降低, ROS、MDA含量和凋亡率升高, SOD活性、MMP和线粒体ATP含量降低, p-YA...     

丙泊酚诱导血红素氧化酶-1表达抑制氧糖剥夺大鼠海马神经元凋亡及机制研究

目的 研究丙泊酚诱导血红素氧化酶-1(HO-1)蛋白表达抑制氧糖剥夺海马神经元凋亡的机制.方法 将培养7d的新生(出生24～48 h)SD大鼠海马神经元随机均分为五组:C1组,海马神经元全量换液后再继续培养24 h;C2组,海马神经元接受50μmol/L丙泊酚处理1h后,再继续培养24 h;D组,海马神经元进行缺糖缺氧培养1h后复糖复氧,再继续培养24 h;P组,海马神经元缺糖缺氧的同时接受50 μmol/L丙泊酚处理;Z组,在海马神经元进行缺糖缺氧的同时加入锌原卟啉(ZnpplX)使其终浓度为10 μmol/L后处理同P组.每组分别取12孔海马神经元,用Hoechst33342染色法检测细胞凋亡,用免疫细胞化学染色法检测HO-1蛋白和Bcl-2蛋白的表达.结果 与C1组比较,C2、D及P组海马神经元HO-1和Bcl-2蛋白的表达均增加,D、P及Z组凋亡率显著升高(P＜0.05或P＜0.01).与D组比较,P组海马神经元HO-1和Bcl-2蛋白表达均增加,凋亡率下降(P＜0.01).与P组比较,Z组海马神经元HO-1和Bol-2蛋白的表达均降低,凋亡率则明显升高(P＜0.01).结论 丙泊酚通过诱导氧糖剥夺海马神经元表达HO-1,进而上调Bcl-2,从而抑制氧糖剥夺海马神经元的凋亡,可能是丙泊酚神经保护作用的机制之一.     

异丙酚不同时机给药对大鼠海马缺氧复氧损伤神经元胞浆细胞色素c的影响

目的 评价异丙酚不同时机给药对大鼠海马缺氧复氧损伤神经元胞浆细胞色素c浓度(Cty c)的影响.方法 原代培养大鼠海马神经元,采用随机数字表法,将其随机分为5组(n=5):对照组(C组)、缺氧复氧损伤模型组(M组)和异丙酚不同时机给药组(Ⅰ组、Ⅱ组和Ⅲ组).采用缺氧6h再复氧的方法制备海马神经元缺氧复氧损伤模型.Ⅰ组、Ⅱ组和Ⅲ组分别于缺氧前、复氧即刻和复氧2 h(T0～2)时加入异丙酚至终浓度20 μmol/L.各组分别于T1,2和复氧24 h(T3)时观察细胞凋亡情况,检测胞浆Cytc的浓度.结果 与C组相比,M组T1-3时、Ⅰ组、Ⅱ组和Ⅲ组T1,2时细胞胞浆Cty c浓度升高(P＜0.05);与M组相比,Ⅰ组T1-3时、Ⅱ组和Ⅲ组T1.2时细胞胞浆Cty c浓度降低(P＜0.05);与Ⅰ组相比,Ⅱ组和Ⅲ组T1,2时细胞胞浆Cty c浓度升高(P＜0.05);与Ⅱ组相比,Ⅲ组T2时细胞胞浆Cty c浓度升高(P＜0.05).不同时机异丙酚给药组细胞凋亡数目较M组明显减少.结论 异丙酚不同时机给药可减少线粒体Cty c释放到胞浆,抑制海马神经元凋亡,减轻缺氧复氧损伤,缺氧前给药效果较好.     

内皮祖细胞源性外泌体对氧糖剥夺-复氧复糖神经元损伤的影响

目的评价内皮祖细胞源性外泌体对氧糖剥夺-复氧复糖神经元损伤的影响。方法培养HT22小鼠海马神经元, 采用随机数字表法分为3组(n=30):对照组(C组)、氧糖剥夺-复氧复糖组(OGD/R组)和氧糖剥夺-复氧复糖+内皮祖细胞源性外泌体组(OGD/R+EXO组)。C组细胞正常培养, OGD/R组采用无糖无血清DMEM培养基在94%N2-1%O2-5%CO2混合气体培养6 h进行氧糖剥夺, 随后更换正常培养基进行复氧复糖24 h。OGD/R+EXO组于氧糖剥夺-复氧复糖造模前24 h在培养基中加入20 μg/ml内皮祖细胞源性外泌体。采用免疫荧光染色法鉴定内皮祖细胞, Western blot法、透射电镜、纳米颗粒追踪分析法鉴定外泌体。采用CCK-8法检测神经元活力, ELISA法测定MDA含量和SOD活性, TUNEL染色法检测神经元凋亡率, Western blot法检测凋亡相关蛋白的表达。结果培养细胞为内皮祖细胞, 成功提取内皮祖细胞源性外泌体。与C组相比, OGD/R组和OGD/R+EXO组神经元活力降低, MDA含量升高, SOD活性降低, 神经元凋亡率升高, Bax表达上调, B...     

异丙酚预处理对乳鼠肝细胞氧-糖缺失/恢复时凋亡的影响

目的探讨异丙酚预处理对乳鼠肝细胞氧-糖缺失/恢复时凋亡的影响及其机制。方法出生1～3 d健康SD乳鼠30只、体重7～11 g,雌雄不拘,提取乳鼠肝细胞,用10%胎牛血清的高糖DMEM培养基孵育6 d后,随机分为5组（n=6）,空白对照组（C组）;单纯氧-糖缺失/恢复组（O组）建立氧-糖缺失/恢复模型;不同浓度异丙酚预处理组（P25组、P50组、P100组）分别用含终末浓度为25、50、100μmol/L的异丙酚培养液预处理后建立氧-糖缺失/恢复模型。观察肝细胞凋亡情况,采用免疫组织化学方法测定肝细胞Bcl-2蛋白、p53蛋白的表达。结果与C组比较,O组、P25组、P50组、P100组的肝细胞凋亡率增加,Bcl-2蛋白表达下调,p53蛋白表达上调;与O组比较,P25组、P50组、P100组的肝细胞凋亡率降低,Bcl-2蛋白表达上调,p53蛋白表达下调（P〈0.01）,且呈浓度依赖性。结论异丙酚25、50、100μmol/L预处理对氧-糖缺失/恢复的乳鼠肝细胞具有保护作用,且呈浓度依赖性,其机制可能与下调p53蛋白的表达和上调Bcl-2蛋白的表达有关。     

二氮嗪预处理对缺氧复氧后大鼠海马神经元凋亡的影响

目的研究线粒体内膜ATP敏感性钾通道（Mito-KAw）特异性开放剂二氮嗪预处理对缺氧复氧后大鼠海马神经元凋亡的影响。方法取离体培养的大鼠海马神经元，随机分为4组：对照组（A组）、二氮嗪30μmol／L组（B组）、二氮嗪1（30μmol／L组（C组）、二氮嗪100μmol／L＋Mito-KATP特异性阻断剂5．羟葵酸100μmol／L组（D组），各组神经元每天给予相应药物预处理1h，连续3d，继而缺氧4h复氧24h，观察神经元的活力、凋亡率、Bax和Bd．2蛋白的表达水平。结果与其它3组比较，C组海马神经元活力增强，凋亡率降低，Bcl．2蛋白表达水平升高，Bax蛋白表达水平下降（P〈0．01）。结论100μmol／L二氮嗪预处理通过改善Bcl-2与Bax蛋白表达的失衡，降低神经元的凋亡，对大鼠海马缺氧复氧神经元产生了保护效应。     

丙泊酚对儿童红细胞抗氧化酶系统的影响

目的观察不同浓度丙泊酚对儿童红细胞抗氧化损伤的保护作用。方法采集20例健康儿童动脉血制成压积红细胞．分为五种不同浓度丙泊酚组（12．5、25、50、75、100μmol／L）（Ⅰ～Ⅴ组）、单纯过氧化氢损伤组（Ⅵ组）和空白对照组（Ⅶ组）．孵育后测各组谷胱甘肽还原酶（GR）活力、谷胱甘肽（GSH）含量。结果Ⅵ组GR活力、GSH含量显著降低,丙泊酚浓度〈50μmol／L时,GSH含量、GR活性Ⅱ、Ⅲ、Ⅳ、Ⅴ组与Ⅵ组及Ⅶ组相比显著增加;当丙泊酚浓度〉50μmol／L时,GSH含量、GR活性皆呈下降趋势。结论一定浓度的丙泊酚可增强儿童红细胞谷胱甘肽抗氧化酶系统活性。     

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.