缺氧诱导因子-1α反义寡核苷酸对胶质瘤细胞化疗敏感性的影响

目的研究缺氧诱导因子(HIF)1α反义寡核苷酸(ASODN)对人胶质瘤细胞化疗药物敏感性的影响。方法人工合成HIF1αASODN经阳离子脂质体包裹后瞬时转染人胶质瘤细胞株U251。采用RTPCR和免疫细胞化学检测转染后HIF1α基因表达,噻唑蓝(MTT)检测细胞增殖抑制率(PI),亚啶橙/溴化乙锭(AO/EB)染色及末端标记法(TUNEL)检测U251细胞转染后顺铂诱导的细胞凋亡指数(AI)。结果HIF1αASODN转染使U251细胞HIF1α基因表达明显下调,其AI和PI分别为(42.0±3.5)%和(72.5±4.8)%,,与各对照组比较均差异有统计学意义(P<0.01),而空白对照组,脂质体组和SODN组的AI和PI分别为(7.1±0.3)%,(8.2±0.2)%,(12.3±0.4)%和(30.7±2.9)%,(34.2±3.5)%,(38.6±3.1)%,AI和PI在各对照组之间的差异无统计学意义(P>0.05)。结论阳离子脂质体转染HIF1αASODN具有促进化疗药物诱导胶质瘤U251细胞凋亡及增强化疗药物敏感性作用。     

热休克蛋白70 反义寡核苷酸对膀胱癌细胞系EJ细胞对丝裂霉素C敏感性的影响

目的　了解热休克蛋白 70 (HSP70 )反义寡核苷酸增强膀胱癌细胞系EJ细胞对丝裂霉素C (MMC)敏感性的作用。方法　用 10 μmol/LHSP70反义寡核苷酸封闭EJ细胞HSP70mRNA ,将 5 0μg/L的MMC与其共培养 ,采用逆转录 聚合酶链反应技术检测HSP70mRNA表达的降低情况 ,四甲基噻唑蓝试验和集落形成试验检测EJ细胞的生长情况。以正义寡核苷酸、无义寡核苷酸处理及未处理EJ细胞为对照。结果　经HSP70反义寡核苷酸处理的EJ细胞 ,HSP70mRNA的表达 (吸光度值为 132± 18)明显低于经正义、无义寡核苷酸处理的细胞 (吸光度值分别为 312± 2 3、32 5± 12 4 ,U值分别为95、10 1,均P <0 0 1) ;对MMC的敏感性 ,细胞生长抑制率、细胞集落抑制率分别为 (5 4 3± 12 3) %和(5 1 8± 12 6 ) % ,明显高于相应的正义 [(11 2± 3 6 ) %和 (13 4± 4 6 ) % ,U值分别为 86、98,均P <0 0 1]、反义寡核苷酸处理的细胞 [(9 6± 2 3) %和 (10 4± 3 0 ) % ,U值分别为 110、10 6 ,均P >0 0 1]。结论　HSP70反义寡核苷酸能增强膀胱癌细胞系EJ细胞对MMC的敏感性。     

黏着斑激酶对胶质瘤细胞生物学行为的影响

目的探讨反义黏着斑激酶（FAK）对U251人胶质瘤细胞株生物学行为影响。方法以LipofecTAMINE^TM介导的反义FAK寡核苷酸转染U251人胶质瘤细胞株，用Western blot检测胶质瘤细胞株FAK含量的改变，研究其多种细胞生物学行为的变化。结果脂质体介导FAKODN转染率为85．9％。转染反义FAK后，U251人胶质瘤细胞株FAK表达明显减少。U251细胞生长抑制率为64．52％，侵袭细胞下降至21．7个，细胞周期分析显示s期细胞降至25．16％。细胞凋亡率升至34．5％。透射电镜观察到凋亡细胞。结论反义FAK寡核苷酸可显著降低FAK在U251中的表达，降低FAK表达能够显著抑制U251人胶质瘤细胞株侵袭能力，抑制细胞增殖和诱导凋亡。     

肝细胞生长因子受体反义寡核苷酸对胶质瘤生长的抑制作用

有研究证实肝细胞生长因子受体c-Met和胶质瘤的发生、进展关系密切[1,2]我们针对c-Met的反义寡核苷酸对人胶质瘤U251细胞进行体内外抑瘤研究,探讨将c-Met作为恶性胶质瘤基因治疗靶基因的可能性.     

树状高聚物介导寡聚核苷酸转染人脑胶质瘤细胞的体外研究

目的评价聚酰胺-胺型树枝状高聚物(PAMAM-dendrimer,PAMAM-D)作为靶向表皮生长因子受体(EGFR)的荧光标记反义寡核苷酸(ASODN)转染人脑恶性胶质瘤体外细胞系U251的可行性及优化方案。方法应用电泳结合实验筛选PAMAM-D与反义EGFR寡核苷酸最佳结合N/P比值,通过荧光显微镜动态观察、逆转录-聚合酶链反应(RT-PCR)评价PAMAM-D转染相同剂量ASODN至人脑恶性胶质瘤体外细胞系U251的效果,噻唑蓝(MTT)染色法间接反映各转染试剂的细胞毒性。结果(1)电泳结合实验显示电荷比(N/P)大于16:1时ODN才能与PAMAM完全结合。(2)动态荧光显微镜观察发现PAMAM-D-ASODN呈颗粒状分布在细胞质内,而oligo- fectamin—ASODN形态均匀。(3)RT-PCR结果显示PAMAM-D和oligofectamin介导的靶向EGFR的ASODN转染的U251细胞的EGFR表达明显下调;MTT法分析证明PAMAM的细胞毒性与oligo- fectamin的基本相当(P>0.05),PAMAM-D-ODN的毒性随电荷比的增大而增大。结论PAMAM- D可以作为寡聚核苷酸的投递载体成功转染人脑胶质瘤细胞。     

反义MDM2联合紫杉醇对胶质瘤细胞U251的作用及其机制

目的探讨MDM2反义寡核苷酸联合紫杉醇对U251人胶质瘤细胞株的作用。方法以Lipofectamine介导的MDM2反义寡核苷酸转染U251人胶质瘤细胞株，免疫组织化学法检测胶质瘤细胞株MDM2蛋白的改变，噻唑蓝（MTT）检测细胞增殖，流式细胞仪检测凋亡，Western blot检测野型生p53（wild typ p53，wtp53）的表达，构建荷胶质瘤裸鼠模型，采用瘤内注射和腹腔给药方式，以MDM2反义寡核苷酸联合紫杉醇治疗，研究其联合抗肿瘤作用。结果脂质体介导反义MDM2 ODN转染U251人胶质瘤细胞株后，MDM2表达减少，与紫杉醇联合使用可增加细胞的凋亡率，野型生p53的表达量增加，裸鼠动物试验联合治疗组瘤重显著小于单独用药组及对照组。结论MDM2反义寡核苷酸可显著降低MDM2在U25I中的表达，引起细胞凋亡，MDM2反义寡核苷酸与紫杉醇联合作用U251人胶质瘤细胞株具有协同作用。     

LRIG3基因过表达对神经胶质瘤细胞株U251与U87增殖及增殖细胞核抗原和Ki-67表达的影响

目的 探讨过表达LRIG3基因对神经胶质瘤细胞株U251与U87增殖及增殖细胞核抗原(PCNA)和Ki-67表达的影响及其机制。方法 用携带LRIG3过表达特异性序列和只含空白载体的质粒用慢病毒法感染胶质瘤细胞株U251与U87,筛选稳定株,分别分成实验组和对照组,通过逆转录-聚合酶链反应(RT-PCR)和Western blot法检测各组细胞LRIG3表达的变化,应用噻唑蓝(MTT)比色法检测病毒感染后对胶质瘤细胞株U251与U87增殖的影响,用免疫组织化学链霉亲和素生物素复合物(SABC)法分别检测各组细胞中PCNA和Ki-67的表达差异。结果 LRIG3过表达组细胞中LRIG3 mRNA水平与对照组比较分别升高67.6％( U251)和79.9％ (U87),LRIG3蛋白表达水平分别升高62.3％(U87)和91.0％( U251)。MTT法结果显示两实验组细胞增殖率均低于相应对照组。U251细胞对照组PCNA阳性率为(47.81 ±4.67)％,实验组为(27.49±3.17)％,U87细胞对照组PCNA阳性率为(55.50±4.01)％,实验组为(33.60±4.82)％,差异均有统计学意义(P＜0.05)。U251细胞对照组中Ki-67的阳性率为(48.50±6.11)％,实验组为(24.30±3.76)％,U87细胞对照组Ki-67阳性率为(55.20±4.19)％,实验组为(23.50±4.60)％,差异均有统计学意义(P＜0.0l)。结论 LRIG3基因过表达可减少胶质瘤细胞的增殖。     

反义DcR3寡核苷酸协同顺铂诱导胶质瘤细胞凋亡

目的 观察陷阱受体3(DcR3)反义核苷酸(ASODN)与顺铂对胶质瘤细胞的影响.方法 设计DcR3反义核苷酸,转染U251细胞,逆转录-聚合酶链反应(RT-PCR)、Western blot方法观察DcR3 mRNA和蛋白有无降低,用噻唑蓝(MTT)比色法、荧光显微镜DAPI染色分别检测对照组、顺铂组、反义核苷酸组、协同作用组对胶质瘤细胞U251的影响.结果 反义DcR3寡核苷酸组可有效地降低DcR3 mRNA和蛋白表达,DcR3/β-actin比值分别为(12.4±3.1)%和(13.5±4.2)%,错义链组、脂质体组、对照组mRNA和蛋白分别为(68.8±4.5)%、(74.5±5.0)%、(71.3±6.4)%和(78.2±6.8)%、(79.8±4.5)%、(76.4±5.6)%,差异有统计学意义(P<0.05).顺铂与反义寡核苷酸组细胞凋亡率分别为(18.32±2.32)%和(20.43±3.45)%,较对照组(5.21±0.45)%,差异有统计学意义(P<0.05),两者与协同处理组(45.23±6.78)%比较,差异有统计学意义(P<0.05).结论 DcR3反义核苷酸与顺铂协同作用可有较强的促胶质瘤细胞凋亡作用.     

脂质体转染碱性成纤维细胞生长因子-mRNA的反义寡核苷酸对大鼠前列腺组织的影响

目的探讨脂质体介导的碱性成纤维细胞生长因子(bFGF)mRNA的反义寡核苷酸(ASODN)对大鼠前列腺组织的影响。方法将45只SD大鼠随机分为反义组、正义组和对照组,向大鼠前列腺组织中分别注入人工合成的bFGFmRNA的反义寡核苷酸脂质体,正义寡核苷酸脂质体和无药脂质体,分别在术后第4、7、14天取出大鼠前列腺,测大鼠前列腺重量及前列腺指数,逆转录聚合酶链反应(RTPCR)检测大鼠前列腺组织中bFGFmRNA的表达,免疫组织化学染色结合计算机图像分析对大鼠前列腺组织中bFGF和增殖细胞核抗原(PCNA)表达进行定量分析。结果将拟给药物注入大鼠前列腺内后7d,正义组大鼠前列腺指数(2.03±0.17)和对照组大鼠前列腺指数(2.02±0.18)相比差异无统计学意义(P>0.05),但均明显高于反义组大鼠前列腺指数(1.62±0.05,P<0.01),正义组bFGFmRNA表达水平(0.5894±0.0245)和对照组bFGFmRNA表达水平(0.6442±0.0569)相比差异无统计学意义(P>0.05),但均明显高于反义组bFGFmRNA表达水平(0.2658±0.0337,P<0.01)。正义组和对照组大鼠前列腺组织中bFGF表达和PCNA指数相比差异无统计学意义(P>0.05),而反义组大鼠前列腺组织中bFGF表达和PCNA指数则显著低于正义组和对照组(P<0.01),且有随时间推移而逐渐下降的趋势。结论脂质体转染bFGFmRNAASODN对     

人脑胶质瘤U251细胞中hMLH1、hMSH2基因启动子区的甲基化状态研究

目的观察人脑胶质瘤U251细胞系中hMLHl、hMSH2基因启动子区的甲基化状态及其在肿瘤发生中的作用。方法采用甲基化特异性聚合酶链反应（MSP）法对人脑胶质瘤U251细胞系的hMLHl、hMSH2基因启动子CpG岛甲基化进行检测；培养人脑胶质瘤U251细胞系，MSP法检测加入5-aza-2’-deoxycytidine前后hMSH2基因在人脑胶质瘤U251细胞中的甲基化状态改变；逆转录．聚合酶链反应（RT-PCR）法检测加入5-aga-2’-deoxycytidine前后hMSH2在人脑胶质瘤U251细胞中的mRNA表达改变。结果人脑胶质瘤U251细胞中未发生hMLHl启动子甲基化，而发生了hMSH2启动子甲基化；5-aza-2’-deoxycytidine处理细胞株后，可逆转hMSH2启动子甲基化，细胞株的mRNA表达增加，加药前后的平均灰度比值分别为（0．40±0．18；0．85±0．32，P〈0．01），差异有统计学意义。结论人脑胶质瘤U251细胞系中hMSH2基因启动子CpG岛高甲基化，5-aza．2’-deoxycytidine能完全逆转hMSH2基因高甲基化状态，可为临床诊断人脑胶质瘤提供新的检测指标和治疗靶点。     

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 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.     

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.     

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.