纳米级全氟丙烷脂质超声微泡造影剂的制备

目的 研制一种新型的直径在纳米级的全氟丙烷脂质超声微泡造影剂,检测其物理特征,探讨并验证其最佳制备条件.方法 以混合的半合成磷脂和全氟丙烷作基本原料,司盘60和吐温80为膜稳定剂,以高剪切分散法制备纳米级超声微泡造影剂.荧光显微镜观察形态分布特点,激光粒度分析仪检测其粒径分布.经均匀设计法及多元回归分析探索各制备条件对超声微泡粒径的影响.结果 经多元回归分析得出高剪切速度和高剪切时间对超声微泡粒径有显著性影响,最优制备条件为:高剪切速度为6档;高剪切时间为8 min;DPPC浓度20 mg/50 ml;T80/S60比值为1,该条件下制备的超声微泡分散均匀、浓度较高,平均粒径为(335±5)nnl.结论 最优条件高剪切分散法制备的超声微泡造影剂粒径分布在208%416 mn之间,是一种达到纳米级的新型超声微泡造影剂.     

负载重组人骨形态发生蛋白-2壳聚糖纳米微球的制备及异位成骨活性研究

目的 制备负载重组人骨形态发生蛋白-2(rhBMP-2)的壳聚糖纳米微球,并考察其成骨活性. 方法 应用离子交联法制备空白壳聚糖纳米微球和rhBMP-2壳聚糖纳米微球,应用透射电镜观察微球的形态,激光粒径分析仪测定其粒径的分布,检测其载药量、包封率及累积释药率.取24只SD大鼠,随机分为4组,每组6只.以无菌手术分别在大鼠左侧股部建立肌袋.A组大鼠肌袋内植入rhBMP-2壳聚糖纳米微球(含rhBMP-2 1 mg),B组大鼠肌袋内植入rhBMP-2 1 mg,C组大鼠肌袋内植入空白壳聚糖纳米微球,D组大鼠肌袋内不做任何处理.评估rhBMP-2壳聚糖纳米微球的成骨活性.结果离子交联法制备的壳聚糖纳米微球球形规整、分散均匀,微球平均粒径为230.0 nm,分布较集中,包封率为66.87％±4.58％,载药率为(33.44±2.29) μg/mg.A、B、C、D组的ALP活性平均分别为(1.94±0 35)、(1.48±0.56)、(0.20±0.07)及(0.18±0.06) kat/g,差异有统计学意义(F=42.959,P=0.000),A、B组明显高于C、D组,且A组高于B组.4组钙含量平均分别为(5.20±1.42)、(3.80±1.40)、(0.19±0.08)、(0.20±0.08)μg/mg,差异有统计学意义(F=39.242,P=0.000),A、B组明 显高于C、D组,且A组高于B组. 结论 离子交联法可成功制备出均一的rhBMP-2壳聚糖纳米微球,该微球具有良好的载药性能和缓释性能,且其骨诱导活性优于单纯rhBMP-2.     

“类乒乓球”状壳聚糖微球的制备及其缓释性能的研究

以液体石蜡作为有机分散介质,采用反相悬浮交联法制备出具有"类乒乓球"结构且粒径近单分散的壳聚糖微球.对产物的形貌及结构进行了初步表征.在模拟肠液的条件下系统研究了壳聚糖微球承载和缓释牛血清白蛋白(BSA)的情况.结果表明,药物的担载效率与初始BSA浓度没有确定的线性关系,但随着初始BSA浓度的增加,吸附量增加;且在释药过程中,不同包药效率对担载有BSA的壳聚糖微球的释放性能影响不大;在模拟肠液条件下,壳聚糖微球吸附BSA的量与BSA溶液的pH值密切相关,实验发现pH=5时,壳聚糖微球吸附BSA的量最大.     

不同时段应用他克莫司纳米微球缓释颗粒促进同种异体神经移植再生的实验研究

目的 探讨不同时间段使用他克莫司(FK506)纳米微球在同种异体移植后促进神经的再生作用.方法 采用单乳化-溶剂挥发法(O/W)制备FK506纳米微球,同种异体移植大鼠胫神经.A组术后立即局部应用FK506纳米微球,B组24 h给药,C组3 d后给药,D组不给药;于术后第4、8和12周行移植神经大体观察、组织学检查及有髓纤维图像分析、小腿三头肌湿重测定、荧光素逆行标记神经元、双侧胫神经电生理比较.结果 FK506纳米微球降解快、吸收好.A、B组神经再生效果相似,都明显要比C、D组好,差异有统计学意义;C、D组之间差异也有统计学意义.结论 FK506纳米微球释药速度符合神经损伤后再生规律,局部应用有良好的促进神经再生作用,而且早期(24 h内)给药效果更加明显.     

负载纳米磁铁颗粒的PLGA微球的可控制备研究

目的采用微流控法制备聚乳酸-羟基乙酸共聚物(PLGA)微球,并同时负载纳米磁铁颗粒,为利用PLGA复合微球实现靶向给药,以及应用MRI进行追踪提供实验基础。方法设计微流控三相装置,用微流控法制备得到PLGAFe_3O_4复合微球,并对所得微球的形貌及Fe_3O_4纳米磁铁颗粒在微球内部的分布情况进行分析测试。结果微流控法制备的PLGA-Fe_3O_4复合微球粒径均一,形貌和分散性好。元素分析结果证实了Fe元素的存在。TEM观察表明,Fe_3O_4纳米磁铁颗粒在微球内部以纳米尺径存在,且分散良好,未出现团聚现象。结论证实了利用微流控法制备负载纳米磁铁颗粒PLGA微球的可行性,为PLGA微球提供了进一步功能化以及靶向给药和MRI追踪的可能性。     

新型纳米微球载碱性成纤维细胞生长因子促进新生血管形成的研究

目的 制备载碱性成纤维细胞生长因子(bFGF)甲基丙烯酸缩水甘油酯修饰葡聚糖纳米凝胶微球,观察其对新生血管生成的诱导和促进作用.方法 采用改良乳液聚合法制备载bFGF纳米微球(bFGF-Dex-GMA-NPs),对纳米微球的外形、包封率、体外释药特征进行常规检测,建立兔后肢缺血模型后,分为以下几组(每组6只):安慰剂治疗组(注射磷酸盐缓冲液)(A组);bFGF治疗组(B组);载bFGF纳米微球组(C组),分别于治疗后7、21 d用99mTc标记的sestamibi对后肢血流进行分析,并于21 d将动物处死,取局部肌肉组织切片进行免疫组织化学染色,镜下对毛细血管计数.结果 合成的纳米微球外形圆整,无相互粘连,包封率高达80.9%,并能较好地控制bFGF的释放,持续释放时间超过25 d.后肢缺血模型治疗第7天,B组和C组能量计数分别为(130.95±14.59)、(127.60±11.36),明显高于A组(27.65±6.82)(P＜0.05),但B组和C组间差异无统计学意义(P＞0.05),第21天,C组能量计数增加到(450.69±21.06),明显高于A组(39.89±8.45)和B组(165.34±15.88)(P＜0.05).免疫组织化学染色结果显示C组毛细血管密度是(99.00±5.44)/mm2,明显高于其他两组2.00±0.59(A组)、13.00±1.35(B组)(P＜0.05).结论 载bFGF纳米微球可以控制bFGF长时间释放,对缺血组织新生血管形成有优于单纯bFGF的诱导和促进作用.     

rhBMP-2明胶纳米微球制备及体外缓释效果研究

目的制备重组人骨形态发生蛋白2(recombinant human bone morphogenetic protein-2,rhBMP-2)明胶纳米微球并检测其体外缓释效果。方法 "二次凝聚法"制备明胶纳米微球,扫描电镜、透射电镜和粒径分析仪检测纳米微球的表面形态、内部结构、粒径,计算其溶胀率;将rhBMP-2与明胶纳米微球复合,计算其包封率和载药量,并对其体外缓释效果进行检测。结果明胶纳米微球的表面形态良好,分散均一,内部结构多孔隙、通道,平均粒径(171.49±50.12)nm,溶胀率为1.83;rhBMP-2明胶纳米微球的包封率为(98.13±0.131)%,载药量为(58.89±0.079)ng/mg;rhBMP-2明胶纳米微球释药时间在1个月以上,呈"双相缓释",第1天为"突释相",释药量约为7%,以后平缓释放呈"缓释相",40%左右的药物于28 d内释放,约60%的药物在1个月以后释放。结论成功制备rhBMP-2明胶纳米微球,不但包封率高,而且体外缓释效果好。     

体外碱性成纤维细胞生长因子聚乳酸纳米缓释微球对人脂肪干细胞增殖和成脂分化的影响

目的 体外观察碱性成纤维细胞生长因子(basie fibroblast growth factor,bFGF)聚乳酸纳米缓释微球对人脂肪干细胞增殖和成脂分化的影响,为bFGF缓释微球应用于脂肪组织工程的研究提供理论依据.方法 体外分离培养脂肪干细胞,并行多向诱导分化鉴定.配制含有0、1、2、3、4、5 mg/ml bFGF聚乳酸缓释微球的脂肪干细胞培养液及成脂分化诱导液.将脂肪干细胞接种至96孔板,第2天更换含不同浓度hFGF缓释微球的培养液和成脂诱导液,分别用四甲基偶氮噻唑蓝比色法(MTT)和油红O定量检测法定期检测细胞增殖和成脂分化的情况.所得数据均用SPSS13.0软件进行统计学处理.结果 bFGF聚乳酸缓释微球有明显促进脂肪干细胞增殖和成脂分化的作用.增殖实验和成脂诱导实验合适的作用浓度分别为3 mg/ml和4 mg/ml.结论 bFGF聚乳酸纳米缓释微球体外可以明显促进脂肪下细胞的增殖和成脂分化,可作为一种较理想的细胞因子缓释系统应用于脂肪组织工程的研究.     

重组人骨形态发生蛋白-2壳聚糖纳米微球的制备及检测

目的 制备负载重组人骨形态发生蛋白-2(rhBMP-2)壳聚糖纳米微球,并检测其粒径、形态、降解及药理特性,以评估壳聚糖纳米微球作为rhBMP-2缓释载体的可行性.方法 以壳聚糖为原料、三聚磷酸钠为交联剂,通过离子交联法制备负载rhBMP-2壳聚糖纳米微球,应用透视电镜观察微球的形态、激光粒径,分析其粒径分布、溶菌酶降解,了解降解特性.通过酶联免疫吸附实验(ELISA)检测rhBMP-2壳聚糖微球的载药率、包封率和释药规律.结果 离子交联法制备的壳聚糖纳米微球,平均粒径大小为230nm,成球性较好,包封率和载药率分别为(66.867±4.575)％、(33.437±2.290)μg/mg;体外释药试验rhBMP-2可以从壳聚糖纳米微球中缓慢释放,释放行为符合双向动力学规律,整个释放过程可达30 d.结论 离子交联法可成功制备壳聚糖纳米微球并具有缓释rhBMP-2的能力,为进一步应用于骨组织工程研究提供实验依据.     

壳聚糖-负载增强型绿色荧光蛋白基因的质粒DNA纳米微球体外转染软骨细胞的能力及影响因素

目的 探讨壳聚糖介导体外基因转染软骨细胞的能力及不同条件下基因转染率的变化,以筛选最佳转染条件.方法 将壳聚糖与负载增强型绿色荧光蛋白(EGFP)基因的质粒DNA(pDNA)以复凝聚法制成壳聚糖/pEGFP纳米微球,用扫描电镜检测纳米微球的形态,Zeta电位粒度分析仪测定其粒径、表面电位及分散度.以脂质体为对照,观察对软骨细胞的毒性.体外转染兔关节软骨细胞,以裸pDNA及脂质体为对照,流式细胞仪及荧光显微镜检测基因转染率.检测在不同pH值、N/P比值及pDNA剂量下壳聚糖/pEGFP纳米微球介导对软骨细胞的转染率变化.结果 壳聚糖/pEGFP纳米微球呈球形,平均粒径为(141.5±26.7)nm,表面Zeta电位平均为(17.8±3.9)mV,分散度平均为0.227±0.025.细胞毒性试验显示壳聚糖/pEGFP纳米微球与软骨细胞相容性良好,与脂质体比较差异有统计学意义(P＜0.05).体外转染实验证实壳聚糖/pEGFP纳米微球能转染软骨细胞并在细胞内表达绿色荧光蛋白,在pH值为7.0、N/P为5、pDNA浓度为4.0μg/mL时基因转染率最高,48 h转染率达10.9％±0.2％.结论 复凝聚法制备的壳聚糖/pEGFP纳米微球是一种有效的非病毒基因转染系统,细胞毒性小,对软骨细胞有一定基因转染能力,其转染率与pH值、N/P比值及pDNA剂量等密切相关,pH值为7.0、N/P为5、pDNA浓度为4.0 μg/mL是其最佳转染条件.     

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.     

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.     

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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

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.