新型多肽神经组织工程支架与背根神经节细胞联合培养的研究

目的 观察自组装含IKVAV多肽凝胶材料与神经组织的生物相容性.方法 肽溶于NaOH溶液中,调整pH至8.5,浓度为0.01g/ml,加DMEM/F12在盖玻片上触发多肽自组装为凝胶,透射电镜检测.取新生SD大鼠背根神经节及其游离细胞分为实验组与对照组,实验组中DRG及其游离细胞与凝胶材料联合培养.倒置相差显微镜观察DRG生长情况,免疫荧光染色结合镜下细胞计数检测凝胶材料的细胞毒性和黏附性.结果 透射电镜显示:自组装凝胶为编织状纳米纤维.实验组中DRG轴突生长情况优于对照组.培养1、3d后,两组中活细胞比例差异无统计学意义.培养3、12h后,实验组中神经细胞黏附数显著高于对照组.结论 含IKVAV多肽凝胶材料能促进DRG生长和神经细胞黏附,对细胞毒副作用小,可作为优良的神经组织工程支架材料.     

自组袭多肽纳米支架与骨髓间充质干细胞的生物相容性研究

[目的]合成神经活性多肽IKVAV(isoleucine-lysine-valine-alanine-valine,异亮氨酸-赖氨酸-缬氨酸-丙氨酸-缬氨酸)两亲性分子,在体外进行自组装纳米纤维支架,并检测其与骨髓间充质干细胞(mesenchymal stemcells,MSCs)的生物相容性。[方法]IKVAV多肽两亲性分子委托上海波泰生物科技公司合成,并用高效液相色谱仪和质谱仪进行纯化和分析。将IKVAV多肽两亲性分子溶于0.1 M NaOH溶液中,加入稀盐酸降低pH值引发自组装,并利用透射电镜进行观察。分离兔骨髓间充质干细胞,流式分析其表面抗原标志。将MSCs与自组装支架体外共培养12 d,测定细胞粘附率,MTT方法检测IKVAV自组装材料对细胞生长增殖的影响,观察其生物相容性。[结果]IKVAV-PA可在一定条件下自组装形成凝胶,透射电镜可见其显示为纳米纤维,其直径为7.0～8.0 nm。分离的MSCs细胞表面标志CD105、CD44、CD34和CD45的阳性率分别为99.3%、99.5%、0.1%、0.4%。共培养过程后,随着时间延长,MSCs在多肽凝胶支架上黏附率上升,吸光度增加,细胞活性增强。[...     

骨髓基质干细胞在IKVAV多肽纳米纤维凝胶表面增殖、黏附及向神经细胞诱导分化的研究

目的研究骨髓基质干细胞（BMSCs）与IKVAV多肽纳米纤维凝胶复合的细胞假体应用于脊髓损伤治疗的可行性。方法合成IKVAV多肽两亲性分子，进行自组装，用透射电镜检测。将IKVAV多肽纳米纤维凝胶与BMSCs复合培养，采用倒置显微镜下观察、Calcein—AM／PI染色、CCK-8法、免疫荧光双标法，检测IKVAV多肽对BMSCs增殖、黏附及向神经细胞方向诱导分化的影响。结果IKVAV多肽可成功自组装成纳米纤维凝胶，其与BMSCs复合培养细胞生长良好，活细胞数达90％以上，IKVAV多肽对BMSCs增殖没有影响，可促进BMSCs的黏附，并在诱导BMSCs向神经细胞分化过程中提高神经元分化比例。结论BMSCs在IKVAV多肽纳米纤维凝胶材料表面可良好的增殖及黏附，并可提高其向神经细胞分化过程中神经元的分化比例。     

神经干细胞与功能化自组装多肽水凝胶的细胞相容性

目的 制备功能化自组装多肽水凝胶并检测其与神经干细胞(NSCs)的生物相容性.方法 合成自组装多肽RADA16 与多肽RADA16-IKVAV,将两者混合制备功能化自组装多肽水凝胶,用原子力显微镜(AFM)观察其形态学特征.采用无血清培养法从新生大鼠皮层分离培养NSCs.将NSCs分别接种到RADA16自组装多肽水凝胶(对照组)与功能化自组装多肽水凝胶(实验组)表面.激光扫描共聚焦显微镜(LSCM)观察细胞迁移.用CCK-8法测定吸光度(A)检测细胞增殖能力.应用Nestin、MAP2、GFAP和CC-1免疫荧光染色,检测神经干细胞分化.结果 AFM显示功能化自组装多肽水凝胶由纳米纤维组成,其纤维直径为20～30 nm,长度可达数百纳米.在细胞接种6 d后,对照组和实验组细胞在水凝胶中的迁移距离分别为(27.5±3.7)μm和(53.2±5.4)μm,两组差异有统计学意义(P＜0.05).复合培养7 d后,实验组中细胞A值明显高于对照组(P＜0.05).免疫荧光结果显示13 d后对照组中MAP2阳性细胞百分率为(22.44±3.52)%,实验组为(40.35±4.84)%,两组差异有统计学意义(P＜0.05).结论 功能化自组装多肽水凝胶与NSCs相容性良好.     

FGL多肽自组装纳米纤维与神经干细胞生物相容性研究

目的 观察组织工程支架材料FGL多肽组装纳米纤维和神经干细胞(neural stem cells,NSCs)的生物相容性. 方法同相法合成FGL多肽两亲性分子(FGL peptide-amphiphile,FGL-PA),采用高效液相色谱仪和质谱仪进行纯化和分析.加入0.1mol/LHCI于FGL-PA溶液,降低pH值引发其自组装,透射电镜观察自组装后的材料.取新生1 d大鼠大脑皮质,培养大鼠NSCs,分别加入最终浓度为0、50、100、200、400 mg/L FGL-PA,采用CCK-8试剂盒检测FGL-PA对细胞增殖的影响.将NSCs分别加入分化培养基(对照组:DMEM/F12、2?7和10?S)和含FGL-PA的分化培养基(实验组:DMEM/F12、2?7、10?S和100 mg/L FGL-PA)诱导分化,采用免疫荧光法检测FGL-PA对NSCs分化的影响. 结果 FGL-PA可自组装形成凝胶,透射电镜示其为纳米纤维,直径为10～20 nm,长度可达数百纳米.加入各浓度FGL-PA 48 h后,当FGL-PA浓度为50、100、200 mg/L时,吸光度(A)值显著增加,差异有统计学意义(P＜0.05).NSCs诱导分化培养14 d,免疫荧光结果 显示对照组NSCs分化为神经元比例为46.35%4±1.27%,实验组为72.85%±1.35%,两组比较差异有统计学意义(P＜0.05). 结论 FGL-PA能自组装形成纳米纤维凝胶,具有良好的生物相容性和生物活性.     

人工合成IKVAV多肽对星形胶质细胞增殖和Neurocan基因表达的影响

【摘要】 目的 观察人工合成IKVAV多肽对星形胶质细胞增殖及硫酸软骨素蛋白多糖核心蛋白Neurocan基因表达的影响,并探讨IKVAV潜在的促进受损脊髓功能恢复的作用。 方法 设计IKVAV序列,人工合成IKVAV多肽,将星形胶质细胞接种于1% IKVAV包被的培养板上,分别于培养1 d、3 d、5 d、7 d、9 d后在激光共聚焦显微镜下观察IKVAV多肽和星形胶质细胞的组织相容性,用CCK8法检测星形胶质细胞增殖情况,用荧光定量PCR法检测星形胶质细胞硫酸软骨素蛋白多糖核心蛋白Neurocan的表达,并与对照组比较,进行统计学分析。 结果 与对照组相比,实验组培养板上星形胶质细胞总数明显减少,但细胞存活率＞95%。荧光定量PCR结果显示实验组星形胶质细胞Neurocan的表达量较对照组显著降低。 结论 人工合成IKVAV多肽可抑制星形胶质细胞增殖、下调硫酸硫酸软骨素蛋白多糖的表达,从而抑制受损脊髓胶质瘢痕的形成,促进脊髓功能恢复。     

异亮氨酸-赖氨酸-缬氨酸-丙氨酸-缬氨酸多肽纳米纤维对神经干细胞生物学行为的影响

目的制备异亮氨酸-赖氨酸-缬氨酸-丙氨酸-缬氨酸（IKVAV）多肽材料并检测其对神经干细胞（NSC）的生物学行为的影响。方法合成IKVAV多肽两亲性分子，进行自组装，用透射电镜（TEM）检测。培养NSC，加入IKVAV，用CCK．8检测吸光度（A值）显示NSC活性。同时检测IKVAV对NSC黏附、分化和轴突生长的影响。结果成功合成IKVAV并自组装成为凝胶，TEM显示为纳米纤维，直径7～8nm，长度可达到数百纳米。当IKVAV浓度为20mg／g和60mg／L时，A值有明显增加，和对照组相比差异有统计学意义（P〈0．01）。加入IKVAV后，神经球黏附率由4％上升到96％，神经球分化率由6％上升到100％，向神经元分化的比率由4．5％提高到5．6％，同时促进神经轴突生长。结论IKVAV可形成纳米纤维，并且具有良好的神经生物活性，是一种优良的神经生物材料。     

人工合成IKVAV多肽对星形胶质细胞增殖和Neurocan基因表达的影响

目的观察人工合成IKVAV多肽对星形胶质细胞增殖及硫酸软骨素蛋白多糖核心蛋白Neurocan基因表达的影响,并探讨IKVAV潜在的促进受损脊髓功能恢复的作用。方法设计IKVAV序列,人工合成IKVAV多肽,将星形胶质细胞接种于1%IKVAV包被的培养板上,分别于培养1 d、3 d、5 d、7 d、9 d后在激光共聚焦显微镜下观察IKVAV多肽和星形胶质细胞的组织相容性,用CCK-8法检测星形胶质细胞增殖情况,用荧光定量PCR法检测星形胶质细胞硫酸软骨素蛋白多糖核心蛋白Neurocan的表达,并与对照组比较,进行统计学分析。结果与对照组相比,实验组培养板上星形胶质细胞总数明显减少,但细胞存活率〉95%。荧光定量PCR结果显示实验组星形胶质细胞Neu-rocan的表达量较对照组显著降低。结论人工合成IKVAV多肽可抑制星形胶质细胞增殖、下调硫酸硫酸软骨素蛋白多糖的表达,从而抑制受损脊髓胶质瘢痕的形成,促进脊髓功能恢复。     

含FGL活性片段的自组装多肽支架材料修复大鼠脊髓损伤的研究

目的 建立大鼠脊髓损伤模型,将含FGL功能化多肽自组装神经支架材料(FGL-NS)植入到脊髓损伤局部,探讨FGL-NS神经支架材料修复脊髓损伤的效果和机制.方法 麻醉大鼠后,暴露胸10水平脊髓,用特制血管夹(夹力24g)钳夹1 min,建立大鼠胸髓钳夹损伤模型.设立空白组、对照组和实验组,分别于损伤后24h,暴露脊髓损伤局部,将2.5μl等渗葡萄糖溶液、1％ RADA-16和1％ FGL-NS多肽溶液注射入损伤局部.术后3d、1、3、5、7和9周分别采用Basso-Beattie-Bresnahan(BBB)评分评估大鼠脊髓损伤经治疗后运动功能恢复情况,术后9周取脊髓损伤部位组织,行半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3、神经丝蛋白-200 (NF-200)和胶质纤维酸性蛋白(GFAP)免疫组织化学染色评估损伤部位细胞凋亡、轴突再生和瘢痕形成情况.结果 成功建立大鼠胸髓钳夹损伤模型.BBB运动学评分大鼠脊髓损伤后经FGL-NS材料治疗后,BBB评分随时间逐渐升高,自伤后第5周起,显著高于RADA-16治疗组和空白组,大鼠运动功能显著改善.免疫组织化学染色结果显示,损伤后第9周,FGL-NS治疗组脊髓损伤局部可见大量NF-200阳性的神经元细胞[(35.32±3.12)个/视野],显著高于RADA-16组[(18.56±2.64)个/视野]和空白组[(14.83±1.43)个/视野],Caspase-3阳性的凋亡细胞[(22.45 ±2.74)个/视野]显著少于RADA-16组[(30.86 ±3.75)个/视野],而且损伤区GFAP染色的积分吸光度(IA)值为0.50±0.02,明显小于对照组(1.30 ±0.09)和空白组(1.60±0.11).结论 功能化多肽自组装神经支架材料FGL-NS能促进脊髓损伤大鼠的运动功能恢复,能减少脊髓损伤部位细胞凋亡,促进神经元再生,并减少胶质瘢痕形成.     

自组装多肽纳米凝胶支架三维培养前软骨干细胞的实验研究

目的构建新型自组装多肽纳米凝胶支架RGDmx,探讨支架的细胞相容性及其对前软骨干细胞(precartilaginous stem cells,PSCs)增殖和向软骨细胞方向分化的影响。方法取新生SD大鼠四肢长骨干骺端组织分离培养PSCs,采用免疫磁珠分选系统分选纯化原代细胞,并进行鉴定。取KLD-12、KLD-12-PRG多肽冻干粉,以体积比1∶1复合构建RGDmx。将纯化后的第3代PSCs接种至KLD-12(对照组)和RGDmx(实验组)培养,1、3、7、14 d用细胞计数(cell counting kit,CCK)-8法检测支架细胞增殖-毒性;制备不同混合比(0、20%、40%、60%、80%、100%)RGDmx,观察其对PSCs增殖的影响;采用无血清软骨形成培养液(complete chondrogenic medium,CCM)诱导两组支架内PSCs向软骨细胞方向分化,培养14 d时行甲苯胺蓝染色法鉴定,并用RT-PCR法检测两组软骨分化特异性基因Ⅱ型胶原和蛋白聚糖的表达情况。结果成功分离纯化获得成纤维细胞生长因子受体3表达阳性细胞,免疫组织化学染色及免疫荧光染色鉴定为PSCs。CCK-8检测结果显示,复合培养后实验组细胞吸光度(A)值随培养时间延长逐步提高,7 d达峰值;其中7、14 d时细胞A值高于对照组(P<0.05);复合培养7 d时,混合比为40%组细胞A值较其他混合比组高,差异有统计学意义(P<0.05)。CCM诱导培养14 d时,两组支架内细胞甲苯胺蓝染色均呈阳性;RT-PCR检测示实验组细胞Ⅱ型胶原和蛋白聚糖mRNA表达水平均高于对照组,差异有统计学意义(P<0.05)。结论自组装多肽纳米凝胶支架RGDmx具有良好的细胞相容性,可有效促进PSCs增殖及向软骨细胞方向分化,是组织工程较理想的细胞载体系统。     

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.     

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.     

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.