吸入麻醉药预处理对兔缺血再灌注心肌Bcl-2、Bax及p53基因表达的影响

目的探讨吸入异氟醚、七氟醚及地氟醚预处理对兔在体心脏局部缺血再灌注过程中心肌细胞Bcl-2、Bax及p53基因表达的影响。方法 40只新西兰白兔随机分成5组(n=8):假手术对照组(P组)、缺血再灌注对照组(IR组)、异氟醚预处理组(Ⅰ组)、七氟醚预处理组(S组)、地氟醚预处理组(D组)。除P组外,每组接受左冠脉前降支3 h阻断和3 h再灌注。吸入药预处理组在缺血前分别吸入1MAC的异氟醚、七氟醚或地氟醚,30 min后洗脱15 min。取心肌缺血区边缘组织用流式细胞仪测凋亡指数(AI)和Bcl-2、Bax及p53基因的蛋白表达量。结果 AI:P组为(0.93±0.27)％,IR组为(14±4)％,I、s、D组较IR组显著减少,分别为(6.7±1.8)％、(6.7±1.6)％、(7.4±2.0)％(P<0.01)。Bcl-2、p53、Bax基因的蛋白表达:Bcl-2基因的蛋白表达量I、S、D组高于IR组,Bax基因和p53基因的蛋白表达量I、S、D组低于IR组。结论 异氟醚、七氟醚及地氟醚预处理抑制缺血再灌注所致心肌细胞凋亡与上调BcI-2基因的蛋白表达、下调p53和Bax基因的蛋白表达有关。     

异丙酚预先给药对全脑缺血再灌注大鼠脑的保护作用

目的观察异丙酚预先给药对大鼠全脑缺血再灌注后细胞凋亡、脑源性神经营养因子(BDNF)及其受体酪氨酸激酶B(TrkB)mRNA表达的影响,在分子水平上探讨异丙酚对全脑缺血再灌注大鼠脑的保护作用及机制。方法 采用Pulsinelli-Brierley四动脉阻断法制备全脑缺血模型。雄性wistar大鼠57只,体重250-300 g,随机分为假手术组(SH组,n=15);缺血再灌注组(ISC组,n=21);异丙酚预处理组(PPC组,n=21),缺血前静脉注射异丙酚50 mg·kg-1后,用微量泵以1 mg·kg-1·min-1持续静注异丙酚2 h。每组按不同再灌注时间随机分为三个亚组:6 h、24 h、72 h亚组。缺血20 min后,于相应的再灌注时间点断头取脑,脑组织标本切片行HE染色,计数海马CA1区存活细胞数;原位末端标记(TUNEL)法检测凋亡细胞,计算凋亡指数;采用原位杂交技术测定BDNF及TrkB mRNA在海马CAl区表达的阳性率。结果HE染色光镜检查,PPC组海马CAl区锥体细胞核固缩、缺失等改变较ISC组明显减轻。(1)存活细胞数:各6h亚组差异无显著性;ISC及PPC组的24 h、72 h亚组低于SH组,ISC组又低于PPC组(P<0.05)。(2)凋亡细胞指数:ISC组及PPC组的6 h亚组低于24 h、72 h亚组。24 h亚组又低于72 h亚组(P<0.01);ISC组6 h、24 h、72 h亚组均高于SH、PPC组,PPC组6 h亚组与SH组差异无显著性,24 h及7     

诱导型一氧化氮合酶在异氟醚延迟相预处理心肌保护中的作用

目的研究诱导型一氧化氮合酶(iNOS)在异氟醚延迟相预处理心肌保护中的作用。方法新西兰白兔36只随机分成五组:异氟醚预处理组(n=9),异氟醚持续吸入2h;1400Wa组(n=6),给予选择性iNOS阻滞药1400W;1400Wb组(n=6),于缺血-再灌注前30min给予1400W;异氟醚 1400W组(n=6),给予异氟醚持续吸入2h,在缺血-再灌注前30min给予1400W;对照组(n=9),给予生理盐水。各组建立心肌局部缺血-再灌注模型。监测缺血-再灌注期间血流动力学参数,测定心肌梗死范围,检测iNOS基因水平表达和蛋白表达。结果异氟醚预处理组[(23.98±2.65)%]和对照组[(42.14±3.06)%]相比明显减少心肌缺血-再灌注后心肌梗死范围(P<0.01),异氟醚 1400W组[(42.12%±2.60)%]和异氟醚预处理组相比,1400W可以取消异氟醚的减少心肌梗死范围的作用(P<0.01)。iNOS在基因水平和蛋白表达水平均增加。结论异氟醚延迟相预处理具有抗心肌缺血-再灌注损伤的作用,而且这种作用是由iNOS所介导。     

异氟烷预处理对离体大鼠浅低温缺血再灌注心肌线粒体耐受性的影响

目的探讨异氟烷预处理能否诱导浅低温缺血再灌注心肌线粒体耐受。方法采用SD大鼠离体心脏Lange-ndroff灌注模型。建立离体大鼠31℃低温全心缺血55min,常温再灌注60min损伤模型。SD离体大鼠心脏随机分为4组(n=10/组):对照组(CON)用K-H液灌注50min后31℃低温缺血55min,常温复灌60min。异氟烷预处理组(ISC1、ISC2、ISC3),分别在缺血前给予0.5%、1.0%、2.0%的异氟烷预充饱和的K-H液灌注15min及洗脱15min。再灌注末,立刻分离心肌线粒体。观察指标有:LVEDP、LVSP、dp/dtmin、dp/dtmax、HR、梗死面积、线粒体和胞浆的细胞色素C。结果同对照组相比,复灌30min及60min时,各组LVSP、dp/dtmin、dp/dtmax、HR均无显著差异,仅ISC3组的LVDEP显著低于CON组(P<0·05)。复灌60min后ISC2组和ISC3组梗死面积显著低于CON组和ISC1组(P<0·05)。异氟烷预处理使浅低温缺血再灌注后心肌线粒体细胞色素C的释放减少。与CON组相比ISC3组胞浆细胞色素C的量明显减少(P<0·05),同时伴随线粒体的细胞色素C显著增加(P<0·05),ISC2组线粒体细胞色素C的量也显著多于CON组(P<0·05)。结论异氟烷预处理能通过诱导线粒体耐受(以线粒体细胞色素C丢失为线粒体功能障碍指标)抗心肌浅低温缺血再灌注损伤。     

缺血预处理对大鼠胰腺移植缺血/再灌注损伤的保护机制

目的探讨缺血预处理对大鼠胰腺移植缺血/再灌注损伤的保护机制。方法建立SD大鼠糖尿病模型。取糖尿病大鼠24只,随机分为缺血/再灌注组(I/R组,n=6)和缺血预处理组(IPC组,n=18),IPC组又平均分为3个亚组:IPC1组(阻断脾血管5min,再灌注5min)、IPC2组[(阻断脾血管5min,再灌注5min)×2次]和IPC3组[(阻断脾血管5min,再灌注5min)×3次]。另取健康SD大鼠6只作为对照组,仅打开腹腔,不做胰腺移植;I/R组和IPC组大鼠均行同种胰腺移植。检测各组胰腺移植再灌注后2h后移植胰组织中超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)的活性;用原位末端脱氧核糖核酸转移标记(TUNEL)法观察移植胰组织的细胞凋亡情况;WesternBlot法检测移植胰组织Bcl-2和Bax基因表达情况。结果IPC各组与I/R组相比较,前者移植胰组织中SOD活性明显升高,MPO活性明显降低,细胞凋亡指数明显降低,Bcl-2表达明显升高,Bax表达明显降低,各项检测指标比较,差异均有统计学意义(P<0.05)。IPC各组中又以IPC2组的各项检测指标差异更为显著(P<0.05)。结论缺血预处理可以减少移植胰缺血/再灌注后的细胞凋亡,IPC2组的效果更为突出。其机制可能与缺血预处理减轻嗜中性粒细胞(PMNs)粘附与聚集、减少氧自由基、上调Bcl-2基因和下调Bax基因的表达有关。     

异氟醚预处理和异丙酚预处理对大鼠心肌缺血再灌注损伤的影响

目的 评价异氟醚预处理和异丙酚预处理对大鼠心肌缺血再灌注损伤的影响.方法 雄性Wistar大鼠36只,体重250～300 g,随机分为4组(n=9):缺血再灌注组(I/R组)、异氟醚预处理组(Ⅰ组)、异丙酚预处理组(P组)和异氟醚预处理联合异丙酚预处理组(I+P组).Ⅰ组异氟醚预处理方法:吸入1.6%异氟醚10 min,停止吸入5 min,共重复2次;P组异丙酚预处理方法:静脉输注异丙酚37.5 mg·kg~(-1)·h~(-1) 10 min,停止输注5 min,共重复2次;I+P组同时进行异氟醚预处理和异丙酚预处理.预处理后立即结扎左冠状动脉前降支60 min,随后松开进行再灌注,I/R组只进行缺血再灌注.再灌注120 min时每组取1只大鼠,取心肌组织,透射电镜下观察心肌细胞超微结构;各组其余大鼠处死后,取左心室,采用TUNEL法测定心肌细胞凋亡情况,计算凋亡指数,并测定心肌细胞线粒体活性氧(ROS)水平.结果 各组均可见凋亡小体,I组、P组和I+P组心肌损伤程度轻于I/R组.与I/R组比较,I组、P组和I+P组心肌细胞凋亡指数和ROS水平降低(P＜0.05),而I组、P组和I+P组间上述指标比较差异无统计学意义(P＞0.05).结论 异氟醚预处理或异丙酚预处理及两种方法联合应用时减轻大鼠心肌缺血再灌注损伤的效应相似.     

不同剂量乳化异氟醚预处理对大鼠局灶性脑缺血再灌注损伤的影响

目的 探讨不同剂量乳化异氟醚预处理对大鼠局灶性脑缺血再灌注损伤的影响.方法 雄性SD大鼠96只,体重250～300 g,采用大脑中动脉线栓法制备大鼠局灶性脑缺血再灌注模型.大鼠随机分为6组(n=16),假手术组(S组)腹腔注射生理盐水(NS)10.5 ml/kg,24 h后只分离血管;缺血再灌注组(I/R组)腹腔注射NS 10.5 ml/kg,24 h后制备模型;低剂量乳化异氟醚预处理组(L组)、中剂量乳化异氟醚预处理组(M组)、高剂量乳化异氟醚预处理组(H组)和脂肪乳剂组(IL组)分别腹腔注射8%乳化异氟醚3.5 ml/kg+NS 7.0 ml/kg、8%乳化异氟醚7.0 ml/kg+NS 3.5 ml/kg、8%乳化异氟醚10.5 ml/kg和30%脂肪乳10.5 ml/kg,24 h后制备模型.于缺血前10 min和再灌注10 min时记录体温、心率和呼吸频率.再灌注24 h时行神经功能缺陷评分,然后取脑组织,测定脑梗死体积,行凋亡细胞计数,并观察脑组织病理学结果.结果 大鼠脑缺血再灌注时体温升高,心率加快,呼吸频率减慢.与S组比较,其余各组神经功能缺陷评分、脑梗死体积和凋亡细胞计数均升高(P＜0.05);与I/R组比较,L组、M组和H组神经功能缺陷评分、脑梗死体积和凋亡细胞计数均降低(P＜0.05),IL组差异无统计学意义(P＞0.05);L组、M组和H组神经功能缺陷评分、脑梗死体积和凋亡细胞计数依次降低(P＜0.05).结论乳化异氟醚可减轻大鼠局灶性脑缺血再灌注损伤,且呈剂量依赖性.     

吸入麻醉药预处理对兔心肌缺血再灌注中心肌细胞凋亡的影响

目的：探讨异氟醚、七氟醚、地氟醚预处理对心肌缺血再灌注过程中心肌细胞凋亡的影响。方法：48只新西兰白兔随机分成6组（n=8)：假手术对照组（P组）、心肌缺血再灌注对照组（IR组）、缺血预处理组（IP组）、异氟醚预处理组（I组）、七氟醚预处理组（S组）、地氟醚预处理组（D组）。除P组外，每组均接受左冠脉前降支3h阻断和3h再灌注。IP组在缺血前接受连续3次每次缺血5min、再灌注5min的预处理，吸入药预处理组在缺血前分别吸入1MAC的异氟醚、七氟醚或地氟醚30min后洗脱15min。取心肌缺血区边缘组织用琼脂糖电泳检测DNA梯带的形成，用流式细胞仪测凋亡指数（AI）。结果：心肌梗死范围占缺血范围的百分比及AI，IP、I、S及D组较IR组显著减少（P＜0．05）。IR组DNA梯带的形成明显，IP、I、S、D组减弱、变模糊。结论：异氟醚、七氟醚、地氟醚预处理能抑制心肌缺血再灌注所致的心肌细胞凋亡。     

异氟醚和卡托普利联合预处理对兔心肌缺血-再灌注细胞超微结构的影响

目的观察异氟醚、卡托普利联合预处理对兔心肌缺血-再灌注心肌细胞超微结构的作用。方法新西兰大白兔48只,随机均分为六组:假手术组(S组)、单纯缺血-再灌注组(IR组)、缺血预处理组(IPC组)、异氟醚组(I组)、卡托普利组(C组)和异氟醚、卡托普利联合预处理组(IC组)。采用结扎冠状动脉左前降支法制备兔心肌缺血-再灌注模型。观察各组心肌细胞超微结构变化。结果 IPC组心肌细胞损伤轻于IR组,IC组损伤最轻。结论异氟醚、卡托普利联合预处理对缺血-再灌注兔心肌细胞超微结构有更好的保护作用。     

异氟醚预处理对局灶性脑缺血再灌注损伤大鼠缺血半暗带TLR4-MyD88信号通路的影响

目的 探讨异氟醚预处理对局灶性脑缺血再灌注损伤大鼠缺血半暗带TLR4-MyD88信号通路的影响.方法 成年雄性SD大鼠54只,体重250 ～ 280 g,采用随机数字表法,将其随机分为3组(n=18):假手术组(S组)、脑缺血再灌注组(I/R组)和异氟醚预处理组(IP组).S组仅分离血管不留置线栓;I/R组采用线栓法制备右侧局灶性脑缺血再灌注损伤模型,缺血2h,再灌注24 h;IP组吸入2.0％异氟醚2h,预处理结束后24h时制备右侧局灶性脑缺血再灌注损伤模型.于再灌注24 h时行神经功能缺陷评分,随后处死大鼠,每组随机抽取5只大鼠,取脑组织,测定脑梗死体积,采用Westernblot法和RT-PCR法检测大鼠右侧脑缺血半暗带区HSP60、TLR4、MyD88蛋白及mRNA的表达情况;每组剩余的3只大鼠,采用TUNEL法检测大鼠右侧脑缺血半暗带区细胞凋亡情况.结果 与S组比较,I/R组和IP组神经功能缺陷评分升高,脑梗死体积增大,右侧脑缺血半暗带区凋亡指数升高,HSP60、TLR4、MyD88蛋白及mRNA表达均上调(P＜0.05);与I/R组比较,IP组神经功能缺陷评分降低,脑梗死体积减小,右侧脑缺血半暗带区凋亡指数降低,HSP60、TLR4、MyD88蛋白及mRNA表达均下调(P＜0.05).结论 异氟醚预处理可保护脑缺血再灌注大鼠缺血半暗带,其机制可能与抑制大鼠脑缺血半暗带TLR4-MyD88信号通路有关.     

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.