抑肽酶预处理对兔脊髓缺血再灌注损伤的影响

目的:观察抑肽酶预处理对兔脊髓缺血再灌注损伤的影响,为临床应用抑肽酶治疗脊髓缺血再灌注损伤提供实验依据.方法:6月龄国产大耳白兔39只,随机分为A组(15只)、B组(15只)和C组(9只).A、B组动物于左肾动脉下用主动脉环扎器环扎腹主动脉,缺血60min后开放,再灌注24h.A组于缺血前10min静脉注射抑肽酶3×107IU/kg,继而用Graseby 3500微量泵持续注入抑肽酶1×107IU/(kg·h)至处死动物时;B组用生理盐水代替A组的抑肽酶,其余同A组;C组只暴露不夹闭腹主动脉,不给药.A、B组缺血前,缺血5、10、20、60min及再灌注后8h、24h,C组相应时间点,测定各组皮层体感诱发电位(CSEP).A、B组缺血前,缺血再灌注后8h、24h,C组相应时间点,处死动物,取L2～L4脊髓行一氧化氮(NO)及一氧化氮合酶(NOS)测定,取L3～L4脊髓灰质切片进行组织学检查,观察神经无形态变化.结果:A、B两组缺血5min时CSEP的P1波和N1波潜伏期较缺血前延长、波幅降低(P<0.05),缺血20min时两波潜伏期及波幅消失,缺血冉灌注后8h两波潜伏期及波幅有所恢复,但较缺血前及缺血后5min、10min时明显延长和降低(P<0.01),缺血再灌注后24h两波潜伏期及波幅较前面各时间点延长和降低(P<0.01);缺血再灌注后8h、24h,A组较B组P1波和N1波潜伏期短、波峰高(P<0.05),而C组较A、B组潜伏期短、波峰高(P<0.01).A、B两组NO、总NOS及诱导型NOS(iNOS)在缺血再灌注后8h明显升高,24h时更高(P<0.05),在缺血再灌注后8h、24h时A组的NO、总NOS及iNOS较B组低(P<0.01).各时间点C组P1波和N1波潜伏期及波幅不变,NO、总NOS及iNOS量均不变(P>0.05).A、B组脊髓缺血再灌注后神经元均有损伤,但在再灌注后8h、24h时A组神经元损伤程度均较B组为轻:C组神经元正常.结论:抑肽酶预处理可以改善脊髓缺血再灌注早期的CSEP,减少NO含量,从而减少缺血再灌注损伤.     

缺血后处理对兔脊髓缺血-再灌注损伤的保护作用

目的研究缺血后处理是否可以减轻兔脊髓缺血再灌注的损伤。方法雄性新西兰大白兔30只,随机分为五组,每组6只。假手术组(N1组)仅行单纯手术操作但不阻闭腹主动脉;对照组(N2组)行单纯缺血再灌注;缺血后处理15s/30s/60s(PA/PB/PC组)分别于阻闭腹主动脉15min后,再灌注15s/30s/60s,缺血15s/30s/60s,反复3次。再灌注48h时对所有动物的后肢运动功能进行评分并行脊髓前角正常神经元计数。结果PB组再灌注48h后肢运动功能评分[3.5(2～4)分],明显高于N2组[2(1～3)分](P<0.05),其他各组与N2组相比差异无显著意义。脊髓前角正常神经元计数PB组为36.7±7.0,明显多于N2组25.7±4.3(P<0.01),而PA组18.2±2.2和PC组8.0±4.1则明显少于N2组(P<0.05)。结论缺血后处理对兔脊髓缺血再灌注损伤的作用取决于后处理时间,缺血后处理30s/30s对脊髓缺血再灌注损伤具有保护作用,而缺血后处理15s/15s和60s/60s会加重脊髓损伤。     

丙泊酚对家兔脊髓缺血-再灌注损伤的保护作用

目的 观察丙泊酚对脊髓组织中低氧诱导因子-1α(HIF-1α)的变化以及神经行为学和脊髓组织病理学改变,探讨丙泊酚对脊髓缺血-再灌注损伤的保护作用.方法 60只新西兰大白兔随机均分为三组:缺血-再灌注组(A组)、缺血-再灌注+英脱利匹特组(B组)、缺血-再灌注+丙泊酚组(C组).采用球囊压迫法建立兔脊髓缺血-再灌注模型.采用Tarlov评分法评价兔复灌后48 h神经行为学功能,显微镜下观察L4～L6脊髓组织的病理生理学改变,采用免疫组化法监测复灌后48、72 h及1周HIF-1α的变化.结果 C组48 h神经行为学Tarlov评分[(3.0±1.3)分]明显高于A组[(1.0±1.2)分]和B组[(1.0±1.1)分](P<0.05),A组与B组差异无统计学意义.神经元计数C组(8.5±3.5)显著高于A组(2.3±2.1)和B组(2.2±2.0).C组HIF-1α表达较其它两组明显增加(P<0.05).结论 丙泊酚能增加脊髓组织HIF-1α的表达,可能促进下游靶基因的表达,使受损组织的血管再生与重建,从而发挥对脊髓缺血-再灌注损伤的保护作用.     

兔脊髓分级缺血-再灌注损伤对体感诱发电位的影响

目的 了解不同程度脊髓缺血-再灌注损伤与体感诱发电位（SEP）、神经功能评分及脊髓病理改变的关系。方法 将40只新西兰大耳白兔随机均分为4组，假手术组、缺血30min组、缺血45min组和缺血60min组。采用腹主动脉阻断法建立兔脊髓缺血-再灌注损伤模型，分别于缺血前、缺血5、10min、再灌注15、30min、1、2、24和48h监测SEP。于再灌注6、12、24和48h进行神经功能评分，再灌注48h进行脊髓病理学观察。结果 阻断腹主动脉血流30、45和60min后开放分别表现为轻、中、重度缺血-再灌注损伤脊髓的病理学改变特点。脊髓轻度缺血-再灌注损伤中SEP波幅和潜伏期分别于再灌注15和30min时恢复至缺血前水平（P〉0．05）；脊髓中度缺血-再灌注损伤中SEP波幅和潜伏期分别于再灌注30min和再灌注1h恢复至缺血前水平（P〉0．05）；脊髓重度缺血-再灌注损伤中SEP波幅和潜伏期分别明显下降和延长，与其他各组组间比较差异有统计学意义（P〈0.01）。各组神经功能评分组间比较差异均有统计学意义（P〈0. 01）。结论 脊髓缺血-再灌注损伤中SEP波幅较潜伏期恢复迅速。术中SEP监测能够敏感而准确地反映缺血-再灌注损伤中脊髓功能的变化，可为临床应用提供实验依据。     

芦荟多糖对脊髓缺血损伤的神经保护作用

目的:探讨芦荟多糖(aloe polysaccharide,AP)对兔脊髓缺血损伤是否有神经保护作用.方法:32只成年雄性新西兰兔随机分成4组(每组8只 ),即对照组(C 组)、芦荟多糖组(A组)、溶剂对照组( V组 ) 及假手术组(S组).A组在脊髓缺血前30min经耳缘静脉给予50m·kg-1芦荟多糖;V组以同样方式给予等容量生理盐水;C组仅仅制备脊髓缺血损伤模型,不进行其它处理;S组仅仅暴露腹主动脉,而不阻断它,其他处理同C组;兔脊髓缺血模型采用夹闭兔腹主动脉肾下段20min.再灌注后48h,对所有动物神经功能评分,然后处死动物取脊髓(L5-7),制作标本行组织病理学观察.结果:A组的神经功能评分和脊髓前角正常神经细胞数明显多于C组及V组(P<0.01);C组及V组的神经功能评分和脊髓前角正常神经细胞数组间无明显差异(P>0.05);神经功能评分与其对应脊髓前角正常神经细胞计数之间有显著相关性(r=0.804,P<0.01).结论:芦荟多糖对兔脊髓缺血再灌注损伤有明显的神经保护作用.     

缺血预处理对兔主动脉阻断后脊髓一氧化氮、后肢神经功能和肌电图的影响

目的　探讨缺血预处理 (IPC)对缺血预处理对兔主动脉阻断后脊髓功能和一氧化氮(NO)的影响。方法　 2 4只日本大白兔随机分为假手术组 (A组 )、缺血再灌注组 (B组 )和IPC保护组 (C组 ) ,每组 8只。分别于首次预处理即刻 (C 40 )、缺血即刻 (I0 )、缺血 45min(I45)、再灌注后 60min(R60 )和术后 7d处死动物前即刻 (R7d)采血检测血清和R7d脊髓组织NO的浓度。术后观察后肢神经功能的评分、后肢针电极肌电图 (EMG)和脊髓组织病理学的改变。结果　缺血再灌注损伤后B组血清NO浓度较缺血前和A、C组对应时点值显著升高 (P <0 .0 1)。C组R7d血清NO浓度明显低于其他时点及A组R7d测定值 (P <0 .0 5或 0 .0 1)。B组脊髓组织NO浓度显著高于A、C组(P <0 .0 1)。B组后肢神经功能和脊髓病理学评分均显著性低于A、C组 (P <0 .0 5或 0 .0 1) ,其后肢EMG亦较C组有显著性病理改变 (P <0 .0 1)。结论　IPC对家兔主动脉阻断后脊髓缺血再灌注损伤有良好的保护作用 ,其保护作用机制与抑制NO的生成有关。     

热激活蛋白70识别蛋白在脊髓缺血再灌注损伤后表达变化及其意义

目的:探讨热激活蛋白70识别蛋白(heat shock cognate protein 70,HSC70)在兔脊髓缺血再灌注损伤(spinal cord ischemia-reperfusion injury,SCIRI)后表达变化及其意义。方法:随机将36只新西兰白兔分成6组(每组6只),采用Zivin法建立兔SCIRI模型。A组只显露腹主动脉而不阻断血流,30min后关闭腹腔,取材(L3~L5段脊髓);B组阻断腹主动脉血流30min后关闭腹腔,取材;缺血再灌注组(C、D、E、F组)阻断腹主动脉血流30min后停止夹闭,再灌注6、12、24、48h时采用改良Tarlov评分分别进行运动功能评价后取材。应用差异蛋白质组学技术荧光差异双向凝胶电泳联合质谱分析筛选出应激相关蛋白HSC70,利用免疫印迹对质谱进行印证,结合免疫组化研究其在脊髓内的时空变化特点。结果:成功建立SCIRI兔模型,SCIRI后实验动物后肢功能逐渐好转,C~F组改良Tarlov评分分别为1.167±0.753、1.667±0.516、2.668±0.516和2.167±0.752分,再灌注24h达SCIRI早期最好水平,再灌注48h略有下降。应激相关蛋白HSC70在A组印迹清晰,B组印迹轻微加强,C组和D组印迹再次加强,E组印迹显著减弱至最低,F组印迹灰度回归至再灌注6~12h水平。A组灰质中部体积较小中间神经元胞浆见轻度免疫反应;B组灰质各部位神经元胞浆免疫反应程度与A组相当;C组胶质细胞核免疫反应加重;D组神经元免疫反应减轻,但胶质细胞及雪旺细胞核免疫反应较强烈;E组神经元免疫反应进一步减弱,低于A组水平;F组神经元胞浆免疫反应加重,胶质细胞及雪旺细胞核免疫反应仍强烈。结论:HSC70参与SCIRI发生和发展过程,可作为SCIRI预防、诊断和治疗的靶点。     

抑肽酶预处理对家兔脊髓缺血再灌注损伤早期脊髓神经功能及病理学的改善

目的 观察抑肽酶预处理对兔脊髓缺血再灌注损伤后早期脊髓神经功能及病理学的影响,为临床应用抑肽酶治疗脊髓缺血再灌注损伤提供实验依据.方法 国产大耳白兔21只,随机分为实验组(8只)、对照组(8只)和假手术组(5只).实验组,缺血60min,再灌注24h,于缺血前10min静脉注射抑肽酶30000kIU/kg,继而用Graseby3500微量泵持续注入抑肽酶10000kIU/(kg·h)直至实验结束.对照组,缺血及再灌注时间、方法同实验组,唯一不同的是对照组用生理盐水代替实验组的抑肽酶.空白组,只暴露腹主动脉,不夹闭,不给药.缺血前、再灌注8h、24h耳缘动脉抽取动脉血3ml形MDA及SOD检查,4h、8h、12h及24h行后肢运动功能评分.再灌注24h处死动物,取动物腰段脊髓(L3-L4)进行病理学处理,光镜、电镜下观察脊髓前角运动神经元数量及形态变化.结果 再灌注后8h、24h,实验组MDA含量明显减少,而SOD活力增加(P<0.05).12h、24h.后肢运动功能改善(P<0.05).病理学观察,脊髓前角运动神经元计数实验组较对照组增高(P<0.05),细胞凋亡减少,形态正常.结论 抑肽酶预处理可以明显降低缺血再灌注后脊髓组织中MDA含量、提高SOD活力、改善后肢运动功能,减少再灌注后细胞的坏死和凋亡,保护神经组织的功能.     

不同高压氧预处理方案对兔脊髓缺血再灌注损伤的影响

目的 探讨不同高压氧预处理方案对兔脊髓缺血再灌注损伤的影响.方法 新西兰大白兔45只,月龄4～5月,体重2.0～2.5 kg,随机分为5组:假手术组(S组,n=5)开腹剥离左肾动脉下段腹主动脉但不阻断血流,20 min后关腹;脊髓缺血再灌注组(IR组,n=10)采用左肾动脉下段腹主动脉阻断法建立脊髓缺血再灌注损伤模型,缺血20 min后恢复灌注;不同方案高压氧预处理组(H_(1～3)组,n=10)分别接受连续5 d(H_1组)、10 d(H_2组)或20 d(H_3组)高压氧预处理(2.5 ATA,吸入氧浓度100%),1h/d,末次高压氧预处理结束后24 h时,建立脊髓缺血再灌注模型.再灌注48 h时,采用修正Tarlov评分,评价后肢运动功能.然后取L_5脊髓节段,分别行HE、TUNEL和nuoro-Jade B染色,计数脊髓正常神经元、凋亡神经元和变性神经元.结果 与S组比较,IR组后肢运动功能评分和脊髓前角正常神经元计数降低(P<0.01);与IR组比较,H_1组和H_2组后肢运动功能评分和脊髓前角正常神经元计数升高,凋亡神经元计数和变性神经元计数降低(JP<0.01),H_3组各指标差异无统计学意义(P>0.05);H_1组和h_2组各指标比较差异无统计学意义(P>0.05);与H_1组和H_2组比较,H_3组后肢运动功能评分和脊髓前角正常神经元计数降低,凋亡神经元计数和变性神经元计数升高(P<0.01).结论 连续5 d或10 d高压氧预处理(2.5 ATA,吸入氧浓度100%)可减轻脊髓缺血再灌注损伤;而连续20 d高压氧预处理无神经保护作用.     

异丙酚对脊髓兴奋性氨基酸含量的影响

目的 观察异丙酚对兔缺血再灌注损伤脊髓的保护作用以及对兴奋性氨基酸(excitatory amino acid,EAA)的影响.方法 健康新西兰大白兔60只,雌雄各半,体重2.0～2.5 kg.采用左肾下腹主动脉阻断法建立脊髓缺血再灌注损伤模型,阻断开始即泵入灌注液6 mL/kg(不足部分均以10%脂肪乳补充),灌注速度12 mL/(kg·h),30 min后停止灌注,开放腹主动脉.根据灌注液的不同,随机分为生理盐水组(A组)、10%脂肪乳组(B组)、30 mg/kg异丙酚组(C组)、40 mg/kg异丙酚组(D组)、50 mg/Kg异丙酚组(E组)及60 mg/kg异丙酚组(F组),每组10只.分别记录麻醉清醒即刻、再灌注后6、24和48 h兔神经行为学评分;于再灌注后48 h取L4～6节段脊髓组织计数脊髓前角正常神经元;采用高效液相色谱法测定脊髓组织中EAA含量.结果 C、D、E、F组各时间点神经行为学评分明显优于A、B组(P＜0.05),E组评分最高(P＜0.05),A、B组间差异无统计学意义(P＞0.05).C、D、E、F组脊髓前角正常神经元明显多于A、B组(P＜0.05),且E组多于C、D、F组(P＜0.05).A、B、C、D、E、F组脊髓组织EAA含量均明显高于正常值,其中A、B组最高(P＜0.05),但A、B组间差异无统计学意义(P＞0.05);E组最低(P＜0.05).谷氨酸、天门冬氨酸含量均与脊髓前角正常神经元计数及再灌注后48 h神经行为学评分成负相关,相关系数分别为-0.613、-0.536、-0.874及0.813(P＜0.01).结论 异丙酚能降低缺血再灌注脊髓组织中EAA含量,减轻脊髓缺血再灌注损伤.     

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.