帕瑞昔布钠对急性心肌梗死大鼠心功能的影响

目的 评价帕瑞昔布钠对急性心肌梗死大鼠心功能的影响.方法 成年雄性SD大鼠24只,体重230～250 g,随机分为3组(n=8):假手术组(S组)、急性心肌梗死组(AMI组)和帕瑞昔布钠组(P组).AMI组和P组采用结扎左冠状动脉前降支的方法制备大鼠急性心肌梗死模型,S组冠状动脉穿线但不结扎;24 h后P组腹腔注射帕瑞昔布钠8 mg/kg,1次/d,连续3 d,AMI组用生理盐水替代.术后第4天测定并记录左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)、左心室收缩压最大上升速率(+dp/dtmax)和左心室收缩压最大下降速率(-dp/dtmax);采集颈总动脉血样3 ml,采用放射免疫法测定血浆血栓素A2(TXA2)和前列腺素I2(PGI2)的浓度,并计算PGI2/TXA2;采血后取左心室心肌组织,测定梗死面积,计算心肌梗死体积.结果 与S组比较,AMI组和P组LVSP、±dp/dtmax、血浆PGI2浓度和PGI2/TXA2降低,LVEDP和血浆TXA2浓度升高(P＜0.05).与AMI组比较,P组LVSP、±dp/dtmax、血浆PGI2浓度和PGI2/TXA2升高,LVEDP和血浆TXA2浓度降低(P＜0.05).AMI组和P组心肌梗死体积比较差异无统计学意义(P＞0.05).结论 帕瑞昔布钠可改善急性心肌梗死大鼠左心室功能,其机制与调节PGI2/TXA2相对平衡有关.     

组织工程心肌补片对黑山羊陈旧性心肌梗死心功能和建立侧支循环的影响

目的探讨自体骨髓间充质干细胞(m arrow m esenchym a l stem ce lls,M SC s)-小肠黏膜下层(sm a llin testina l subm ucosa,S IS)构建的组织工程心肌补片,移植于陈旧性心肌梗死区后对心功能及缺血区建立侧支循环的影响。方法将已建立急性心肌梗死模型后6周的黑山羊16只,随机分为实验组和对照组,实验组抽取自体骨髓,经体外分离M SC s,进行培养、传代,以第3代细胞行5-B rdU标记并与S IS支架材料复合培养5 d,制备M SC s-S IS组织工程心肌补片。将其缝合至陈旧性心肌梗死区;对照组仅行假手术处理。于植入后6周,采用超声心动图观察两组动物心功能变化,数字减影血管造影选择性左冠状动脉造影观察缺血心肌侧支循环的建立。结果术后6周实验组及对照组:心博出量、左心室射血分数分别为42.81±4.91、37.06±4.75 m l和59.20%±5.41%和44.56%±4.23%,组间差异均有统计学意义(P<0.05);左心室舒张末期容积、左室收缩末期容积分别为72.55±8.13、83.31±8.61 m l和29.75±5.98、46.25±6.68 m l,组间差异均有统计学意义(P<0.05);左心室舒张功能各项指标分别为:E峰最大速度分别为54.85±6.35 cm/s和43.14±4.81cm/s(P<0.01);A峰最大速度分别为52.33±6.65 cm/s和56.91±6.34 cm/s(P>0.05)。超声心动图显示对照组左室腔扩张明显,室壁运动明显减弱,梗死区呈瘤样扩张,局部室壁反常运动;实验组左室腔明显小于对照组,室壁运动较对照组强,心尖梗死区扩张不明显。选择性左冠状动脉造影见实验组左冠状动脉前降支远端与回旋支间明显侧支循环建立。结论M SC s-S IS构建的组织工程心肌补片移植于黑山羊陈旧性心肌梗死区后侧支循环建立,心功能有明显改善作用。     

猪心肌非缺血性梗死研究

目的 观察心肌非缺血性梗死发生发展的规律.方法 中国小型猪12头,体重18～20 kg,实验组结扎LAD上等流量点,对照组解剖相应部位LAD外膜(n=6),术中测定左心室心底和心尖部位血流动力学指标.4周后取出心脏标本,将左心室分成17段,4%多聚甲醛固定1周,苏木素-伊红(HE)、PATH及天狼星红染色进行病理学观察.结果 结扎LAD 4周后,左心室17段心肌内均可发现大小不等的梗死灶.左心室腔近心端收缩压收缩压[(264.05±49.34)比(168.35±31.74)mmHg(1 mm Hg=0.133 kPa)]、平均压[(128.65±33.68)比(82.86±14.45)nnnHg、发展压[(255.09±103.18)比(178.70±31.70)nnnHg]与心尖部比较差异有统计学意义(P＜0.05).结论 结扎猪左冠状动脉前降支后,左心室非缺血区域可发生局灶性梗死.     

骨髓间质干细胞移植对香猪急性心肌梗死后心肌结构和心功能的影响

目的 移植自体骨髓间质干细胞(BMSCs)到香猪急性心肌梗死区内,研究移植BMSCs对心肌结构和心功能的影响. 方法将24只贵州香猪采用计算器随机法分为实验组(n＝12)和对照组(n＝12),抽取香猪自体骨髓,经体外分离出BMSCs并培养和经5-氮胞苷(5-azacytidine)转化,利用结扎左前降支(LAD)的方法建立急性心肌梗死动物模型,经LAD和梗死区多点注射的方法将实验组香猪注射BMSCs(细胞总数2×106个),对照组注射等量的细胞培养液.3周和6周后,用超声心动图(UCG)观察两组移植后心肌结构和心功能改变的情况. 结果实验组左心室射血分数、左心室短轴缩短率和室壁增厚率明显高于对照组;左心室室壁、室间隔厚度和心室腔的大小在两组之间也存在明显差别,实验组室壁和室间隔厚度明显大于对照组,而心室腔小于对照组. 结论 BMSCs梗死区心肌移植后可减轻心室重构的进程,减轻心肌的变薄程度,使心室腔未明显扩大.BMSCs移植还可增加心肌的收缩力,改善心功能.     

异丙酚对急性心肌梗死大鼠心脏功能的影响

目的 观察异丙酚对急性心肌梗死大鼠血液动力学影响的量-效关系以及心肌梗死范围和心肌超微结构的变化。方法 将急性心肌梗死模型的大鼠随机分为5组（n=8）,对照组（Ⅰ）,其余大鼠分别持续静脉输注30（Ⅱ）、45（Ⅲ）、60（Ⅳ）、75（Ⅴ）mg·kg-1·h-1异丙酚30min。测定输注异丙酚30min血药浓度,观察血液动力学、心肌梗死范围和心肌超微结构的变化。结果 血药浓度为（3.4±0.9）～（12.9±2.4）μg/ml时,平均动脉压（MAP）、心率（HR）、左室收缩压（LVSP）、左室内压力变化最大速率（±dp/dtmax）、心肌耗氧指数（MOCI）均呈剂量依赖性下降（P<0.05）,左心室舒张末压（LVEDP）无明显变化（P>0.05）,心肌梗死面积为23.7％～29.2％（P>0.05）,心肌超微结构无显著性差异。结论 在血药浓度（3.4±0.9）～（12.9±2.4）μg/ml范围内,异丙酚对血液动力学及心收缩功能呈剂量依赖性抑制,对心肌梗死范围和心肌细胞超微结构无明显影响。     

骨髓基质干细胞治疗兔缺血心肌的初步实验研究

目的通过建立兔自体骨髓移植模型,验证骨髓基质干细胞(MSCs)移植到缺血心肌后是否在心肌的微环境中可以向心肌细胞分化,探讨其对缺血心肌心功能的影响。方法将13只新西兰大白兔分为实验组(7只)和对照组(6只),实验组于心肌梗死前后缘上、中、下各3点分别注射被5溴-2脱氧尿苷(BrdU)标记的自体MSCs(3×106cells/30μl);对照组注射同等量的磷酸盐缓冲液(PBS)。移植4周后通过激光共聚焦显微镜验证移植后的MSCs是否向心肌细胞分化,并用心脏彩色超声心动图和多导生理记录仪测定缺血心肌的心功能。结果移植4周后,MSCs向心肌细胞分化,表达出α-肌小节肌动蛋白(-αsarcomeric actin)和存在于闰盘中的连接蛋白43(connexin 43),自体MSCs能够增加局部心肌组织中血管数量。实验组心肌左心室收缩功能明显比对照组增强[左心室射血分数(LVEF):0.51±0.07 vs.0.43±0.06,左心室侧壁运动幅度(LVLWMD):1.75±0.42mm vs.1.09±0.28mm,左心室收缩期室壁增厚率(LVΔT):0.19%±0.05%vs.0.11%±0.04%,左心室收缩压(LVSP):113.1±6.3 mmHg vs.99.5±5.1 mmHg,左心室舒张期末压(LVEDP):11.5±2.1 mmHg vs.14.3±3.1mmHg,左心室压力增高最大速率(+dp/dtmax):4 618.3±365.2mmHg/s vs.3 268.1±436.9 mmHg/s,左心室压力下降最大速率(-dp/dtmax):3 008.8±346.7mmHg/s vs.2 536.9±380.4 mmHg/s,P<0.05]。结论自体MSCs移植到兔缺血心肌后可以向心肌细胞分化,提高缺血心肌的心功能,对治疗心肌缺血具有较好的前景。     

骨骼肌卫星细胞梗死心肌移植的细胞因子分泌及血管再生作用

目的　研究骨骼肌卫星细胞梗死心肌移植的胰岛素样生长因子(IGF)-1、碱性纤维母细胞生长因子(bFGF)分泌及血管再生的作用。方法　骨骼肌卫星细胞经结扎的冠状动脉左前降支远端灌注移植入梗死区,2、4、8周后取标本,应用免疫组化学方法检测细胞因子表达及梗死区血管密度。结果　骨骼肌卫星细胞移植2、4、8周后梗死区IGF-1和bFGF表达分别为81.68±3.34、96.87±7.78、90.43±7.36及81.87±3.58、65.66±4.57、74.20±6.41,明显高于对照组(P＜0.01);同时,移植2、4、8周后梗死区血管密度高于对照组(P＜0.05)。结论　骨骼肌卫星细胞梗死心肌移植除有心肌再生外,尚可通过细胞因子分泌对梗死心肌起到积极作用。     

颈交感干离断对急性心肌梗死大鼠左室重构的影响

目的 探讨颈交感干离断(TCST)对急性心肌梗死大鼠左室重构的影响.方法 健康清洁级成年雄性SD大鼠64只,体重230～250 g,随机分为4组(n=16):假手术组(S组)、心肌梗死组(MI组)、左TCST组(LT组)、右TCST组(RT组).采用结扎左冠状动脉前降支的方法 制备急性心肌梗死模型.S组只穿线不结扎左冠状动脉前降支,分离颈交感干,不离断;MI组制备心肌梗死模型,随后分离颈交感干,不离断;LT组和RT组在心肌梗死模型制备成功后,分别实施左、右侧TCST.于TCST后第4周,每组随机选取8只大鼠,称重,随后处死,取左心室组织,称量,计算左心室质量指数(左心室质量/体重),并采用体视学三维形态定量分析左室重构情况,测定左心室心肌细胞体积密度(V_v)、心肌组织总体积(V_t)和心肌细胞总体积(V_c),采用RT-PCR测定心肌c-fos mRNA的表达水平.结果 与S组比较,其余各组左心室质量指数增加,心肌c-fos mRNA表达上调,左心室V_t和V_c增大,MI组和LT组左心室V_v增大(P<0.01),RT组左心室V_v差异无统计学意义(P>0.05);与MI组比较,LT组左心室质量指数增加,心肌c-fos mRNA表达上调,左心室V_t和V_c增大(P<0.05或0.01),左心室V_v差异无统计学意义(P>0.05),RT组左心室质量指数降低,心肌c-fos mRNA表达下调,左心室V_v、V_t和V_c减小(P<0.05或0.01);与LT组比较,RT组左心室质量指数降低,c-fos mRNA表达下调,左心室V_v、V_t和V_c减小(P<0.05).结论 右侧TCST可下调心肌梗死大鼠心肌c-fos mRNA的表达,一定程度上抑制左室重构;而左侧TCST可进一步诱导c-fos mRNA表达,促进左室重构的发展.     

高渗灌注对大鼠心肌缺血-再灌注损伤的影响

目的在Langendorff灌注模型上研究高渗灌注对大鼠心肌缺血-再灌注损伤耐受性的影响。方法健康雄性SD大鼠20只,随机分为对照组(C组)和高渗氯化钠灌注组(H组),每组10只。腹腔注射戊巴比妥钠(60mg/kg)麻醉后快速取出心脏接上主动脉插管置于Langendorff装置上,Krebs-Henseleit缓冲液平衡逆行灌注20min。待HR及冠脉流量平稳后夹闭灌注道进行全心热缺血30min,复灌40min。通过多道生理记录仪持续监测HR、左心室压峰值(LVPSP)、左室舒张末压(LVEDP)和左室压力最大上升/下降速率(±dp/dtmax),计算左室发展压(LVDP=LVPSP-LVEDP),用左室发展压与心率乘积(RPP=LVDP×HR)表示左室做功。结果同C组比较,H组再灌注心功能恢复显著改善:HR[(89.5±7.8)%vs(57.9±4.6)%,P<0.05]、LVPSP[(83.5±7.8)%vs(62.9±4.1)%,P<0·05]、RPP[(66.3±9.4)%vs(36.4±3.8)%,P<0.05]、冠脉流量(CF)[(61.2±8.9)%vs(41.9±4.0)%,P<0.05]、+dp/dtmax[(60.4±6.9)%vs(22.9±3.4)%,P<0.01]和-dp/dtmax[(69.5±6.6)%vs(34.3±3.3)%,P<0.01];肌酸激酶(CK)释放量显著降低(P<0.05)。结论高渗灌注减轻心肌缺血-再灌注损伤。     

由胚胎干细胞分化的心肌细胞移植对心肌梗死大鼠左心室重构及心功能的影响

目的探讨小鼠胚胎干细胞（ES）分化的心肌细胞移植对SD大鼠心肌梗死后左心室重构及心功能的影响。方法采用悬滴-悬浮培养法诱导ES分化形成拟胚体。其中包含有大量心肌细胞。将雄性SD大鼠冠状动脉左前降支结扎。制成急性心肌梗死模型。1周后再次开胸。实验组于梗死区域注入心肌细胞悬液150μl（含细胞5×10^5个），梗死对照组于梗死区域注入等体积细胞培养液，另设假手术组，不结扎冠状动脉。心肌梗死后1周和细胞移植后4周，采用超声心动图评价大鼠左心室形态和功能，用免疫荧光技术检测移植细胞的存活及其表型。结果免疫荧光技术检测到分化的心肌细胞表达特异性转录因子α辅肌动蛋白、α肌球蛋白重链和肌钙蛋白1；逆转录聚合酶链反应检测到有心肌特异性转录因子Nkx-2．5、GATA-4及α肌球蛋白重链基因的表达；膜片钳记录显示所得到的分化的心肌细胞包括窦房结样起搏细胞、心房样细胞和心室样细胞。细胞移植后4周。与梗死对照组相比，实验组左心室收缩末期容积和舒张末期容积均显著缩小，左心室前壁舒张末期厚度明显增加（P〈0．01）。左室长轴缩短率显著升高（P〈0．01）。心脏组织冰冻切片可见4,6-联脒-2-苯基吲哚标记的呈蓝色荧光的移植细胞核。移植细胞表达肌钙蛋白I，移植细胞与受者的心肌细胞间有连接蛋白-43的表达。实验组中有2只（12．5％。2／16）出现了心脏畸胎瘤。结论由胚胎干细胞分化的心肌细胞移植可逆转心肌梗死大鼠左心室重构。改善左心室功能。     

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.