不同保存方法对生物衍生骨支架材料细胞相容性的影响

目的了解不同保存方法对生物衍生骨支架材料细胞相容性的影响.方法冻干生物衍生骨用两种不同保存液同等条件4℃冷藏保存3个月,以保存相同时间冻干生物衍生骨为对照.实验分为A组:成骨细胞复合 1号保存液处理材料培养;B组:成骨细胞复合 2号保存液处理材料培养;C组:成骨细胞复合冻干骨培养;D组:单纯成骨细胞培养.以2×106个/ml密度的成骨细胞悬液复合材料培养1、3、5和7天.用倒置相差显微镜和扫描电镜观察细胞的黏附和生长情况、检测细胞活力、碱性磷酸酶(alkaline phosphatase,ALP)活性及流式细胞仪分析细胞周期.结果成骨细胞与三种不同方法保存的材料均可黏附,并在材料孔隙内生长、分化和增殖.复合培养1和3天,各组间无显著差异;复合培养5和7天,黏附于材料的细胞活力大小依次为 A组>C组>B组 (P＜0.01,P＜0.05).复合培养7天,黏附于材料的细胞ALP活性大小依次为 A组>C组>B组(P＜0.01) .各组细胞周期未见明显变化,未见异倍体细胞.结论选择适宜的保存液对生物衍生骨支架材料的细胞相容性有一定优化作用.     

国产多孔钽复合MG63细胞培养Col-1、OC和OPN蛋白表达及意义

[目的]观察国产多孔钽材料复合MG63细胞培养后细胞增殖粘附情况,并检测成骨相关因子Col-1、OC和OPN表达情况,研究国产多孔钽材料的生物相容性,为国产多孔钽的临床应用提供理论依据。[方法]将MG63细胞与国产多孔钽材料复合培养,通过倒置相差显微镜、扫描电镜观察检测细胞粘附情况,MTT法检测细胞增殖情况,免疫细胞化学和免疫蛋白印迹法,检测Ⅰ型胶原(collagen typeⅠ,Col-1)、骨钙素(osteocalcin,OC)和骨桥蛋白(osteopontin,OPN)表达变化情况。[结果]MG63细胞与多孔钽材料复合培养后,细胞增殖情况良好,与对照组比较无差异(P0.05);细胞在材料表面及孔隙内生长粘附并长入孔隙中,并逐渐完全覆盖材料;免疫细胞化学与免疫蛋白印迹结果提示复合培养组出现Col-1、OC表达增强(P0.05),OPN的表达无明显差异(P0.05)。[结论]国产多孔钽材料有利于MG63细胞的黏附、生长,具备良好的生物相容性,并可能影响Col-1、OC的表达。     

脂肪干细胞/Ⅰ型胶原凝胶/聚乳酸聚乙醇酸-β-磷酸三钙骨组织工程复合体的构建及其异位成骨研究

目的 构建基于脂肪干细胞、Ⅰ型胶原凝胶以及聚乳酸聚乙醇酸-β-磷酸三钙支架(PLGA-β-TCP)的骨组织工程复合体并对其异位成骨进行研究.方法 设计构建脂肪干细胞-Ⅰ型胶原凝胶/PLGA-β-TCP复合体(A组),同时设立单纯细胞/PLGA-β-TCP材料复合体(B组)、单纯Ⅰ型胶原凝胶/PLGA-β-TCP复合体(C组)以及单纯PLGA-β-TCP支架材料(D组)作为对照.扫描电镜、相差显微镜观察细胞材料复合情况并对脂肪干细胞增殖以及成骨分化进行分析.体外成骨诱导培养2周后移植于自体股部肌袋,8周后取出,依次行放射学、组织学定性及半定量分析.结果 (1)体外成骨诱导2周,A组细胞增殖率慢于B组(P<0.05,n=4),但其细胞总数远高于后者(P<0.01,n=4).A组碱性磷酸酶(ALPase)活性、细胞外基质矿化程度均显著高于B组(P<0.01,n=4).A组细胞悬浮于Ⅰ型胶原凝胶并均匀分布于材料孔隙中而B组细胞仅见黏附于材料表面.(2)移植8周,X线片示A组高密度钙化影形成,B、C、D组未见有阳性结果.A组材料孔隙中均匀充满新生骨组织,可观察到骨小梁样结构.B组仅在少数孔隙中有类骨组织形成,同时伴有结缔组织长入.A组新生骨面积百分比显著高于B组(P<0.01,n=4).结论 通过应用Ⅰ型胶原凝胶来实现脂肪干细胞与PLGA-β-TCP多孔支架材料的均匀复合,能够有效促进脂肪干细胞在材料孔隙中的成骨分化及均质骨组织形成.     

自体软骨细胞复合Ⅰ型胶原支架体外动态培养的实验研究

[目的]比较体外静态与动态培养两种方式对培养人关节软骨细胞复合Ⅰ型胶原支架材料的效果,从而探索体外构建移植物用于治疗关节软骨缺损的适宜条件及方式。[方法]分离培养人关节软骨细胞,P2代软骨细胞接种于Ⅰ型胶原支架,随机分为3组,A组:静态培养;B组:动态培养;C组:单层培养。采用倒置相差显微镜、荧光显微镜、SEM、HE染色观察细胞在支架上的分布、黏附、生长及形态特点,实时荧光定量PCR检测软骨细胞表型特异基因Ⅱ型胶原的表达情况。[结果]体外单层培养的软骨细胞(P2)以多角形为主,Ⅱ型胶原蛋白表达阳性,提示P2代细胞表型维持良好;与A组比较,B组细胞数量较多且分布均匀,细胞形态较均一,以多角形为主;A、B组样本大体结构及内部孔隙结构均保持完整,孔隙内均可见细胞黏附,B组孔隙内细胞数量及细胞外基质优于A组;A、B组的Ⅱ型胶原基因mRNA表达水平较单层培养组明显增加。[结论]软骨细胞复合Ⅰ型胶原支架体外动态培养较静态培养可明显促进细胞增殖及细胞外基质分泌。因此,动态培养有望成为体外构建自体软骨细胞移植术所需移植物的一种有效方法。     

医用多孔钽材料对大鼠软骨细胞增殖、细胞周期及凋亡的影响

[目的]观察国产多孔钽材料对大鼠软骨细胞增殖、细胞周期及凋亡的影响,为其作为软骨组织工程支架材料临床应用提供实验依据。[方法]选用3周龄SD大鼠双侧股骨头、膝关节分离软骨组织,经Ⅱ型胶原酶消化,饱和湿度培养,传代。倒置显微镜下逐日观察细胞生长状态。待第2代细胞生长至80%左右时,通过甲苯胺蓝染色、番红O-固绿染色以及Ⅱ型胶原免疫细胞化学染色进行软骨细胞鉴定。以F12-DMEM为浸提介质分别制备100%、50%、25%多孔钽浸提液,软骨细胞加不同浓度多孔钽浸提液作为实验组,未加浸提液的软骨细胞作为对照组;MTT法检测多孔钽浸提液对软骨细胞增殖的影响及细胞毒性检测。将第2代软骨细胞接种到多孔钽支架上进行体外三维培养,而对照组是将软骨细胞接种到无支架的培养板上,倒置相差显微镜观察两组软骨细胞生长状态;胰酶消化复合于材料上的软骨细胞,流式细胞仪检测软骨细胞的细胞周期变化及细胞凋亡。[结果]软骨细胞接种初期大小不等,呈圆形悬浮于培养液中,24 h后贴壁细胞伸展呈三角形、多角形等。第7⁹ d待细胞生长呈现融合时即可传代。甲苯胺蓝染色显示软骨细胞胞浆内可见蓝紫色颗粒,番红O-固绿染色显示胞浆呈绿色、细胞核呈紫红色,Ⅱ型胶原免疫细胞化学染色显示阳性信号位于胞浆及部分胞膜,以上方法证实了分离培养的细胞为软骨细胞;MTT法检测显示随着培养时间的延长,各浓度浸提液组细胞生长与对照组无明显差异,软骨细胞形态正常,贴壁增殖良好,相同时间点不同浓度的浸提液与对照组间细胞增殖差异无统计学意义(P>0.05),提示软骨细胞在多孔钽浸提液中生长、增殖状态良好且多孔钽材料无毒性。多孔钽支架材料外观灰色光亮,表面及断面可见分布均匀的蜂窝状孔隙,孔径针尖大,支架材料不透光,将分离培养的第2代软骨细胞接种到多孔钽支架上后,复合培养24 h后,倒置相差显微镜可见材料边缘有少量软骨细胞黏附,细胞呈多角形;随着培养时间增加,材料边缘及培养板底部细胞黏附的数量逐渐增多,边缘软骨细胞生长良好;流式细胞仪检测显示实验组与对照组细胞均为正常二倍体细胞,两组细胞周期分布相似,实验组及对照组的细胞凋亡率及坏死细胞率差异均无统计学意义(P>0.05)。[结论]国产多孔钽材料无毒性,对软骨细胞增殖、细胞周期及凋亡无明显影响,适合作为软骨组织工程支架材料。     

新型钽铌多孔支架材料的细胞生物相容性研究

[目的]研究多孔钽铌(Ta-Nb)材料的细胞相容性。[方法]将兔成骨细胞与多孔钽铌材料共培养,采用CCK-8法检测细胞增殖、扫描电镜观察细胞在材料上的黏附、RT-PCR检测Ⅰ型胶原和骨钙素基因的表达。[结果]CCK-8检测显示实验组多孔钽铌材料上细胞的增殖与空白对照组没有差异性(P﹥0.05);扫描电镜观察到细胞在多孔钽铌的表面和孔隙内大量黏附、增殖和生长,随着共培养时间的增加,材料表面的细胞数量明显增多;RT-PCR显示随着共培养时间的增加,Ⅰ型胶原基因的表达增强(P﹤0.05),骨钙素的表达无明显差异(P﹥0.05)。[结论]多孔钽铌支架材料适于成骨细胞的黏附、生长和分化,具有良好的细胞相容性。     

3D打印PLA-HA复合材料与骨髓基质细胞的相容性研究

目的 探讨骨髓基质细胞与3D打印聚乳酸-羟基磷灰石(Three-dimensional printed polylactic acid-hydroxyapatite,3D printed PLA-HA)复合支架材料的相容性,为骨组织工程选择合适的支架材料提供理论依据。方法将标记绿色荧光蛋白(Green fluorescent protein,GFP)的骨髓基质细胞分别与3D打印PLA-HA复合材料和β-磷酸三钙(betatricalcium phosphate,β-TCP)材料体外复合培养,采用荧光显微镜观察细胞在支架材料上的生长黏附情况,并通过扫描电镜观察细胞在支架中的形态变化;CCK8(Cell Counting Kit8)法检测细胞于不同时间点在材料上的黏附率以及增殖情况;碱性磷酸酶(Alkaline phosphatase,ALP)活性测定法检测3 d、7 d、14 d的碱性磷酸酶活性变化。结果 骨髓基质细胞能够在3D打印PLA-HA复合材料和β-TCP材料上黏附生长;β-TCP组细胞黏附率高于3D打印PLA-HA组(P<0.05),但3D打印PLA-HA组在12 h细胞黏附率可达到60%以上;细胞增殖实验显示,3D打印PLA-HA组在体外培养第4天和第7天的细胞增殖量(OD值)均高于β-TCP组与对照组(P<0.05);3D打印PLA-HA组以及β-TCP组在第3天、第7天和第14天的ALP含量均高于对照组,且3D打印PLA-HA组第7天ALP含量较β-TCP组增多(P<0.05)。结论 3D打印PLA-HA复合材料具有良好的细胞相容性,可作为骨组织工程的支架材料。     

海螵蛸与兔软骨细胞组织的生物相容性

目的 探讨海螵蛸作为新生兔关节软骨体外细胞培养支架材料的可行性.方法 消化分离新生兔关节软骨细胞,接种于自制海螵蛸片支架上培养,从倒置相差显微镜和扫描电镜观察其亲水性和对细胞的吸附力.结果 预湿海螵蛸支架的亲水性优于未预湿海螵蛸支架,使软骨细胞更易扩散至支架孔隙.软骨细胞-支架复合体培养1周后,细胞开始在预湿海螵蛸支架上黏附、伸展、增殖;2周后细胞融合成片,布满整个支架孔隙并产生基质.结论 海螵蛸多孔支架与兔软骨细胞具有良好的生物相容性,可以作为软骨组织工程中细胞培养支架的新材料.     

生物衍生骨支架材料的体外细胞相容性实验研究

目的 评价不同处理方法制备的生物衍生骨支架材料的细胞相容性。方法 将支架材料,即复合型完全脱蛋白骨（CFDB）、部分脱蛋白骨（PDPB）和部分脱钙骨（PDCB）与人胚骨膜来源的成骨细胞体外复合培养,采用倒置相差显微镜、激光共聚焦显微镜、扫描电镜、流式细胞仪及碱性磷酸酶（ALP）活性检测,观察支架材料的细胞相容性。结果 三种材料上皆有细胞附着生长,三种材料对细胞增殖影响大小为PDCB＞PDPB＞CFDB;三种材料对成骨细胞的细胞周期影响较小,未见异倍体细胞;三种材料对成骨细胞ALP活性的影响大小依次为PDCB＞PDPB＞CFDB。结论 CFDB、PDPB及PDCB无细胞毒性、无致瘤性,皆有良好的细胞相容性,以CFDB为最好。三种材料皆可用于骨组织工程的支架材料。     

壳聚糖支架材料与骨髓基质细胞相容性的实验研究

目的 初步探讨壳聚糖支架材料与骨髓基质细胞的生物相容性.方法 壳聚糖制成疏松多孔海绵状支架材料,采用体外复合细胞培养技术,将骨髓基质细胞在壳聚糖支架材料中培养,通过噻唑蓝比色(MTT)法检测细胞增殖情况及碱性磷酸酶活性的检测,观察支架材料对培养细胞的影响.结果 骨髓基质细胞在壳聚糖支架材料中生长良好,细胞增殖和碱性磷酸酶活性在细胞组与支架-细胞组中差异无统计学意义(P＞0.05),表明壳聚糖支架材料对骨髓基质细胞的增殖、分化及分泌功能均无明显影响.结论 壳聚糖支架材料与骨髓基质细胞的生物相容性好,有作为骨组织工程载体材料的应用前景.     

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.     

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.     

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.