小檗碱预先给药对缺氧/复氧诱导人肾小管上皮细胞凋亡的影响

目的 探讨小檗碱预先给药对缺氧/复氧诱导人肾小管上皮细胞凋亡的影响.方法 培养人肾小管上皮细胞(HK-2),以1×106个/ml密度接种于培养皿(2 ml/皿)和96孔培养板(200μl/孔),采用随机数字表法,将其分为4组(n=30):正常对照组(C组)、小檗碱组(B组)、缺氧/复氧组(H/R组)和缺氧/复氧+小檗碱组(H/R+B组).B组和H/R+B组加入10 μmol/L小檗碱孵育2h,随后H/R组和H/R+B组进行缺氧24h复氧3h.测定细胞活力、细胞凋亡率、丙二醛(MDA)、超氧化物歧化酶(SOD)、caspase-3、活化caspase-3、细胞色素c、葡萄糖调节蛋白78(GRP78)和C/EBP同源蛋白(CHOP)表达,并计算Bax表达与Bcl-2表达的比值(Bax/Bcl-2).结果 与C组比较,H/R组和H/R+B组细胞活力、SOD活性和caspase-3表达降低,细胞凋亡率、MDA浓度和Bax/Bcl-2升高,活化caspase-3、细胞色素c、GRP78和CHOP表达上调(P＜0.05),B组上述指标差异无统计学意义(P＞0.05);与H/R组比较,H/R+B组细胞活力、SOD活性和caspase-3表达升高,细胞凋亡率、MDA浓度和Bax /Bcl-2降低,活化caspase-3、细胞色素c、GRP78和CHOP表达下调(P＜0.05).结论 小檗碱预先给药可抑制缺氧/复氧诱导人肾小管上皮细胞凋亡,其机制与抑制线粒体应激通路和内质网应激通路有关.     

肾小管上皮细胞内质网应激时NGAL表达改变的调控机制研究

目的:探讨人肾小管上皮细胞(HK-2细胞)发生内质网应激时,NGAL表达增加的上游调控机制。方法:将HK-2细胞分为对照组(正常HK-2细胞),TG(毒胡萝卜素,thapsigargin)组(5μmol/L TG处理8 h),单纯转染组(siRNAATF4试剂转染24 h),转染+TG组(siRNA-ATF4试剂转染24 h后,5μmol/L TG处理8 h),阴性对照组(siRNA-阴性对照物转染24 h),DMSO组(5μmol/L DMSO处理8 h)。采用Western blot检测各组细胞内质网源性转录因子(CHOP)、内质网分子伴侣葡萄糖调节蛋白78(GRP78)、中性粒细胞明胶酶相关性载脂蛋白(NGAL)、激活转录因子4(ATF4)的表达,采用Real-time PCR方法测得ATF4mRNA、NGALmRNA表达量。结果:与对照组相比,TG组细胞NGAL、ATF4、ATF4mRNA、NGALmRNA表达量显著提高(P <0. 05),而转染+TG组、单纯转染组、阴性对照组、DMSO组中ATF4及NGAL差异无统计学意义(P> 0. 05)。与TG组相比,转染+TG组ATF4、NGAL、ATF4mRNA及NGALmRNA表达量呈显著降低趋势(P <0. 05)。在TG组与转染+TG组细胞中,CHOP和GRP78呈过表达状态(P <0. 05),而转染+TG组细胞CHOP和GRP78提升趋势明显低于TG组细胞(P <0. 05)。结论:(1) TG可诱导人肾小管上皮HK-2细胞发生内质网应激反应。(2) HK-2细胞发生内质网应激反应时,抑制ATF4表达会引起NGAL降低,提示ATF4是NGAL表达的上游调控因子。(3) HK-2细胞发生内质网应激反应时,抑制ATF4不能阻止CHOP和GRP78发生过表达,但可降低其升高程度,提示ATF4及NGAL降低可能对内质网应激反应介导HK-2细胞损伤起到一定的缓解作用。     

纳洛酮对离体人脑神经元神经特异性烯醇化酶的影响

目的 探讨不同浓度纳洛酮对体外培养人脑神经元缺氧损伤后细胞内外神经特异性烯醇化酶(NSE)浓度及NSE信使核糖核酸(mRNA)表达量变化的影响.方法 应用无血清方法原代培养人胚胎大脑神经元,经免疫组化染色证实神经元比例达80%以上,对神经元进行缺氧结合无糖处理.将24孔培养板上的细胞随机分为单纯缺氧1 h组、缺氧+纳洛酮0.25μg/ml组、缺氧+纳洛酮5μg/ml组、缺氧+纳洛酮10μg/ml组和对照组,每组6孔细胞.缺氧处理1 h后复氧,于复氧24 h应用酶联免疫吸附试验(ELISA)测定细胞内外NSE浓度.将25 ml培养瓶内的细胞随机分为单纯缺氧0.5 h组、缺氧+纳洛酮0.5μg/ml组和缺氧+纳洛酮10μg/ml组,缺氧处理0.5 h后复氧,应用逆转录-聚合酶链反应(RT-PCR)观察缺氧及复氧后不同时间细胞内NSE mRNA表达量的变化.结果 ①单纯缺氧1 h组细胞外液NSE浓度明显升高(P＜0.01),给药组随纳洛酮浓度增加,NSE浓度呈现逐渐降低趋势,至5μg/ml恢复至对照组水平.②单纯缺氧1 h组细胞内NSE浓度明显降低(P＜0.01),给药组随纳洛酮浓度增加,细胞内NSE浓度呈现逐渐升高趋势,至10μg/ml恢复至对照组水平.③单纯缺氧0.5 h组,缺氧后NSE mRNA表达量明显升高(P＜0.01),其后逐渐降低,并于复氧24 h后恢复至接近缺氧前水平.给予纳洛酮0.5μg/ml,NSE mRNA表达量在缺氧0.5 h后即刻仍明显升高.给予纳洛酮10μg/ml,NSE mRNA表达高峰延迟至复氧6 h出现.结论 纳洛酮可减轻细胞膜损伤,减少细胞内酶的外漏,并在转录水平调节细胞NSE的表达,发挥对神经元缺氧性损伤的保护作用.     

丙泊酚对胃癌细胞凋亡时GRP78-ATF4-CHOP信号通路的影响

目的评价丙泊酚对胃癌细胞凋亡时葡萄糖调节蛋白78(GRP78)-活化转录因子4(ATF4)-C/EBP同源蛋白(CHOP)信号通路的影响。方法传代培养至对数期的MGC-803细胞,采用随机数字表法分为2组(n=15):对照组(C组)和丙泊酚组(P组)。C组细胞在37 ℃、5%CO2条件下正常培养;P组细胞待贴壁生长至70%～90%时,加入丙泊酚,终浓度为5 μg/ml,24 h时采用流式细胞术检测细胞凋亡率,qPCR法检测GRP78、ATF4和CHOP的mRNA表达,Western blot法检测GRP78、ATF4和CHOP的表达。结果与C组比较,P组细胞凋亡率升高,GRP78、ATF4、CHOP及其mRNA表达上调(P<0.05)。结论丙泊酚促进胃癌细胞凋亡的机制与激活GRP78-ATF4-CHOP信号通路有关。     

血红素加氧酶-1对乳鼠心肌细胞缺氧复氧损伤的影响

目的 探讨血红素加氧酶-1(HO-1)对乳鼠心肌细胞缺氧复氧损伤的影响.方法 新生SD大鼠8只,日龄1～3 d,原代培养心肌细胞,随机分为4组:正常对照组(C组)常规培养8 h;缺氧复氧组(HR组)采用缺氧2 h,复氧6 h的方法制备心肌细胞缺氧复氧模型;血晶素组(Hemin组)缺氧前24 h及缺氧即刻,培养基中加入Hemin,终浓度为20 μmol/L;血晶素+锌原卟啉组(Hemin+ZnPP组)缺氧前24 h及缺氧即刻培养基中同时加入Hemin及ZnPP,终浓度均为20 μmol/L.各组细胞均接种于35 mm培养皿(2 ml/皿)或50 ml培养瓶(3 ml/瓶),每组45皿和3瓶.于复氧结束后采用蛋白印迹法测定心肌细胞HO-1表达,台盼蓝染色法测定心肌细胞存活率,应用全自动生化分析仪测定细胞培养液乳酸脱氧酶(LDH)活性,超声破碎细胞离心后取上清,采用硫代巴比妥酸法测定细胞MDA水平,黄嘌呤氧化酶法测定细胞SOD活性.结果 与C组比较,其余3组培养液LDH活性、心肌细胞MDA水平及HO-1表达升高,心肌细胞存活率及SOD活性降低(P＜0.05).与HR组比较,Hemin组培养液LDH活性、心肌细胞MDA水平降低,HO-1表达、心肌细胞存活率及SOD活性升高(P＜0.05),Hemin+ZnPP组上述指标差异无统计学意义(P＞0.05).HR组和Hemin+ZnPP组细胞缺氧复氧损伤明显,Hemin组细胞缺氧复氧损伤减轻.结论 HO-1可减轻乳鼠心肌细胞缺氧复氧损伤.     

瘦素预先给药对L02肝细胞缺氧复氧时细胞凋亡的影响

目的 探讨瘦素预先给药对L02肝细胞缺氧复氧时细胞凋亡的影响.方法 L02肝细胞接种于6孔培养板中,孵育24 h后,随机分为6组,每组6孔:对照组(C组)、缺氧复氧组(HR组)和不同浓度瘦素预处理组(L_(1～4)组).HR组于37℃95%N_2-5%CO_2培养箱中缺氧12 h,然后于37℃95%O_2-5%CO_2培养箱中复氧12 h;L_(1～4)组先分别加入瘦素100、200,400和800 μg/L,再进行缺氧复氧.取细胞上清液,采用赖氏法测定谷丙转氨酶(ALT)和谷草转氨酶(AST)的浓度;采用Hoechst 33342/PI双染色法测定细胞捌亡情况,计算细胞凋亡率;采用荧光定量PCR法测定Bax mRNA和Bcl-2 mRNA的表达.结果 与C组比较,HR组和L_(1～4)组ALT和AST的浓度升高,早期凋亡率和晚期凋亡率升高,Bax mRNA和Bcl-2 mRNA表达上调(P<0.01);与HR组比较,L_(1～4)组ALT和AST的浓度下降,早期凋亡率降低,L_3组Bax mRNA表达下调,L_2组和L_3组Bcl-2 mRNA表达上调(P<0.01);L_(1～4)组间ALT和AST的浓度、早期凋亡率和晚期凋亡率、Bax mRNA和Bcl-2 mRNA表达差异无统计学意义(P>0.05).结论 瘦素预先给药可抑制L02肝细胞缺氧复氧时细胞凋亡,其机制与上调肝细胞Bcl-2 mRNA的表达,下调Bax mRNA的表达有关.     

缺氧／复氧后肾小管上皮细胞ICAM-1表达及Apocynin对其干预作用的研究

目的：研究缺氧/复氧后肾小管上皮细胞氧化应激的变化细胞间黏附分子-1（ICAM-1）蛋白和mRNA的表达及NADPH氧化酶抑制剂Apocynin对其的影响.方法：采用肾小管上皮细胞（HK2）建立缺氧（细胞置于37 ℃、95%N2、5% CO2环境中）/复氧（细胞置于37 ℃、95% O2、5% CO2环境中）细胞模型,设正常对照组,缺氧0.5 h、1 h、2 h/复氧24 h组,及不同浓度（0.05 mmol/L、0.25 mmol/L、0.5 mmol/L）Apocynin干预组.流式细胞术检测细胞内氧化应激水平,逆转录-聚合酶链反应（RT-PCR）法测定细胞ICAM-1 mRNA表达,流式细胞术检测ICAM-1蛋白表达.结果：缺氧/复氧后HK2细胞内氧化应激水平提高,ICAM-1 mRNA和蛋白表达增强,随缺氧时间的延长,细胞内氧化应激水平逐渐升高,ICAM-1mRNA和蛋白表达也逐渐增强 Apocynin呈剂量依赖关系抑制细胞内氧化应激和ICAM-1 mRNA、蛋白表达的上调.结论：缺氧/复氧诱导细胞内氧化应激的产生,诱导ICAM-1表达上调 Apocynin可以通过抑制细胞内氧化应激抑制ICAM-1的上调.     

缺氧后处理和二氮嗪后处理对大鼠心肌细胞缺氧复氧时钙网蛋白表达的影响

目的 探讨缺氧后处理和二氮嗪后处理对大鼠心肌细胞缺氧复氧时钙网蛋白(CRT)表达的影响.方法 健康雄性SD大鼠,4～5月龄,分离心肌细胞,培养18 h后,随机分为6组(n=8):对照组(C组)、缺氧复氧组(HR组)、缺氧后处理组(HP组)和二氮嗪后处理组(DP组).C组细胞于5%CO2培养箱内继续培养2 h;HR组细胞于95%N2-5%CO2培养箱中缺氧45 min,然后于95%O2-5%CO2培养箱中复氧1 h;HP组细胞于95%N2-5%CO2培养箱中缺氧45 min,然后复氧3 min,缺氧3 min,重复3次,再于95%O2-5%CO2培养箱中复氧1 h;DP组细胞于95%N2-5%CO2培养箱中缺氧45 min,然后给予50 μmol/L二氮嗪处理10 min,再于95%O2-5%CO2培养箱中复氧1 h.测定心肌细胞caspase-3活性、CRT表达和游离钙离子浓度.结果 与C组比较,其余各组caspase-3活性升高,HP组和DP组CRT表达上调,HR组游离钙离子浓度升高(P＜0.05或0.01);与HR组比较,HP组和DP组caspase-3活性降低,CRT表达上调,游离钙离子浓度降低(P＜0.01).结论 缺氧后处理和二氮嗪后处理可上调CRT的表达,减轻细胞内钙超载,减轻大鼠心肌细胞缺氧复氧损伤.     

异丙酚预先给药对BV-2细胞缺氧复氧时TLR4表达的影响

目的 评价异丙酚对BV-2细胞缺氧复氧时Toll样受体4(TLR4)表达的影响.方法 小鼠小胶质细胞(BV-2细胞)于6孔培养板中培养4～6 d后随机分为4组(n=4),正常对照组(C组)不给予任何处理;缺氧复氧组(A/R组)缺氧3 h、复氧12 h;缺氧复氧+25μmol/L异丙酚组(P25组)和缺氧复氧+100μmol/L异丙酚组(P100组)于缺氧前30 min加入异丙酚,终浓度分别为25、100μmol/L.于复氧12 h时收集细胞,测定TLR4 mRNA、NF-κB mRNA和TLR4蛋白水平;收集细胞上清液,测定TNF-α水平.结果 与C组比较,A/R组、P25组和P100组TLR4 mRNA、NF-κB mRNA、TLR4蛋白和TNF-α水平均升高(P<0.01);与MR组比较,P25组和P100组TLR4 mRNA、NF-κB mBNA、TLB4蛋白和TNF-α水平均下降(P<0.01);与P25组比较,P100组TLR4 mRNA、NF-κB mRNA、TLR4蛋白和TNF-α水平均降低(P<0.01).结论 异丙酚25、100 μmol/L预先给药可抑制BV-2细胞缺氧复氧时TLR4 mRNA表达上调.     

异丙酚对缺氧复氧鼠脑神经元NOS活性和HSP70家族表达的影响

目的：通过观察不同浓度异丙酚对原代培养胎鼠大脑神经元缺氧复氧过程的影响，探讨异丙酚的部分脑保护机制。方法：培养12天的胎鼠大脑神经元，随机分为四组：Ⅰ组正常对照组；Ⅱ组缺氧复氧组；Ⅲ组14μmol／L异丙酚组；Ⅳ组56μmol／L异丙酚组。Ⅲ组和Ⅳ组于缺氧前分别换入含有14μmol/L和56μmol／L异丙酚的培养液，随后缺氧30min。四组于缺氧后1h、2h、4h、6h和24h用分光光度法分别比较各组神经元NOS(一氧化氮合成酶)活性，同时四组于缺氧后1h、3h、6h、8h、24h、48h和72h分别用原位杂交法和免疫组化法观察Hsp70(热休克蛋白70)mRNA、Hsc70(热休克同源蛋白70)mRNA及Hsp70的表达。结果：①本研究的缺氧复氧过程可使神经元NOS活性增强，并可诱导Hsp70 mRNA、Hsc70mRNA和Hsp70表达，且表达高峰分别为24h、24h和48h；②在14μmol／L和56μmol／L异丙酚组，缺氧复氧鼠脑神经元NOS活性在复氧后4h内降低；③14μmol／L和56μmol／L异丙酚组的缺氧复氧鼠脑神经元Hsp70mRNA和Hsc70mRNA的表达高峰分别提前至8h和6h，而只有56μmol／L异丙酚组的缺氧复氧鼠脑神经元Hsp70的表达高峰才提前至24h。结论：异丙酚可抑制缺氧复氧引发的神经元NOS活性增强，同时异丙酚可从转录和翻译两个水平上促进鼠脑神经元热休克蛋白70家族的表达。     

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.