胆管癌抗原肽对转染全长野生型p53的树突状细胞免疫功能的影响

目的研究胆管癌抗原肽对转染全长野生型p53的树突状细胞(wtp53DC)免疫功能的影响。方法先将全长野生型p53导入脂质体内并转染小鼠骨髓来源的DC,然后用胆管癌抗原肽修饰wtp53DC,检测这种树突状细胞的抗原提呈功能。结果抗原肽修饰的wtp53DC和单纯DC的上清3种细胞因子含量明显增加,分别为(545.2±12.1)ng/L,(511.1±13.3)ng/L,(537.1±11.1)ng/L(P<0.05);wtp53DC刺激小鼠脾脏T细胞增殖水平明显高于对照组(P<0.01);该细胞高表达B7-1、B7-2、MHC-Ⅰ、MHC-Ⅱ(P<0.05);能够特异性地杀伤胆管癌细胞,杀伤率81.6%。结论全长野生型p53基因转染+胆管癌抗原肽联合修饰树突状细胞能诱导小鼠细胞毒性T淋巴细胞的特异性。     

小鼠端粒酶蛋白亚单位转染树突状细胞体外诱导特异性抗肝癌细胞免疫应答

目的 观察携带小鼠端粒酶蛋白亚单位(mTERT)基因蕈组腺病毒载体(AdmTERT)转染树突状细胞(DC)后诱发免疫效应细胞产生特异性抗肝癌细胞免疫应答的研究.方法 用流式细胞仪分析及电镜观察培养6 d DC的细胞表型及形态,Ad-mTERT重组腺病毒转染体外培养的小鼠DC,Western blot检测mTERT融合蛋白表达;用负载mTERT的DC刺激同型淋巴细胞,免疫磁珠分选CD8~+T细胞做为效应细胞,小鼠肝癌细胞株(H22)及小鼠结肠癌细胞(CT26)作为靶细胞,用酶联免疫吸附试验(ELISA)及酶联免疫斑点法(ELISPOT)检测干扰索(IFN)-γ分泌量和释放抗原特异性IFN-γ的T细胞数,~(51)Cr释放法检测细胞毒性T淋巴细胞(CTL)对肝癌细胞的杀伤活性.结果 细胞表型及形态观察证实小鼠骨髓来源的DC为成熟的树突状细胞;AdmTERT转染DC后能正确表达mTERT融合蛋白,用AdmTERT转染DC致敏的淋巴细胞IFN-γ分泌量(208.6μg/L)和分泌IFN-γ的特异性T细胞的数量(341/10~6脾细胞)都高于Ad-GFP转染的DC组(14.2μg/L,33/10~6脾细胞)和单纯DC组(12.1μg/L,19/10~6脾细胞,P＜0.05).AdmTERT修饰DC刺激产生的效应T细胞在效靶比为90:1时,对H22细胞的杀伤率(54.2%)明显高于AdGFP致敏组(8.2%)和未致敏DC组(4.5%,P＜0.05),而对CT26细胞无明显杀伤作用.结论 AdmTERT修饰的DC体外能够诱导出针对mTERT抗原特异性的CTL效应,可特异性杀伤mTERT阳性的肝癌细胞.     

胆管癌抗原肽对转染全长野生型p53的树突状细胞免疫功能的影响

目的　研究胆管癌抗原肽对转染全长野生型 p5 3的树突状细胞 (wtp5 3DC)免疫功能的影响。方法　将全长野生型 p5 3导入脂质体内并转染小鼠骨髓来源的DC ,然后用胆管癌抗原肽修饰wtp5 3DC ,检测这种树突状细胞的抗原提呈功能。结果　抗原肽修饰的wtp5 3DC和单纯DC这 4种上清 3种细胞因子含量明显增加为 :( 5 45 .2± 12 .1)ng/L ,( 5 11.1± 13 .3 )ng/L ,( 5 3 7.1±11.1)ng/L ;wtp5 3DC刺激小鼠脾脏T细胞增殖水平明显高于对照组 (P <0 .0 1) ;该细胞高表达B7 1、B7 2、MCH Ⅰ、MCH Ⅱ (P <0 .0 5 ) ;能够特异性地杀伤胆管癌细胞 ,杀伤率为 81.6%。结论全长野生型 p5 3基因转染与胆管癌抗原肽联合修饰树突状细胞能诱导小鼠细胞毒性T淋巴细胞的特异性。     

转染肝癌总RNA的树突状细胞疫苗对肝癌的抑制作用及其机制

目的探讨转染肝癌细胞总RNA转染的树突状细胞(DC)疫苗抑制肝癌作用及其机制。方法采用粒/巨噬细胞集落刺激因子(GM-CSF)和白细胞介素(IL)-4联合培养6 d成小鼠骨髓来源不成熟DC(iDC),质脂体转染肝癌细胞系Hepa1-6 RNA入iDC,用LPS刺激后成为Hepal-6 RNA/DC疫苗,对照组为iDC组、LPS/DC组Saline组,以每只2×10~6个细胞腹腔注射免疫小鼠每周1次共3次,然后接种5×10~5 Hepal-6细胞,观察肿瘤生长情况、特异性CTL活性的测定以及抗体阻断实验。结果实验组Hepal-6 RNA/DC组肿瘤在第8周为(8．5±3．6)mm,而iDC组、LPS/ DC组、Saline对照组分别为(36．6±3．6)、(31．3±4．7)、(32．2±4．0)mm,与实验组比较差异均有统计学意义(P＜0．05)。实验组脾细胞对Hepal-6细胞有特异性杀伤效应,而对肺癌LLC细胞无杀伤活性。所诱导的抗肿瘤效应细胞包括CD~(8+)、CD~(4+)T淋巴细胞。结论肝癌细胞的总RNA转染的DC肿瘤疫苗能诱导CD~(8+)、CD~(4+)T细胞免疫,是较有临床应用前景的肝癌免疫治疗方法。     

转存活素基因树突状细胞抗消化道肿瘤的免疫效应

目的研究转染存活素基因对树突状细胞(DC)免疫功能的影响,观察修饰后的DC在体外诱导的抗消化道肿瘤免疫效应。方法脂质体介导存活素基因转染入DC,用蛋白印迹法检测培养上清存活素的表达,检测转存活素基因DC分泌细胞因子白细胞介素12(IL12)、肿瘤坏死因子α(TNFα)的功能,以及经流式细胞仪检测DC表面CD1a、CD83、MHCⅡ、CD80、CD86表达的高低,用噻唑蓝(MTT)法诱导人特异的细胞毒性T淋巴细胞(CTL)的能力。结果培养上清中均可以检测到存活素表达;转存活素基因DC的上清IL12、TNFα含量分别为(2652±327)pg/ml和(4371±835)pg/ml,比单纯DC组高(P<005);CD1a、CD83、MHCⅡ、CD80、CD86等在单纯DC表面低表达,在转基因DC表面高表达;MTT法检测,经转染存活素基因的DC提呈的细胞对胃癌细胞、结肠癌细胞、胆管癌细胞杀伤率分别为65%、77%、85%,而单纯DC杀伤作用较低。结论存活素基因转染修饰的DC能诱导细胞毒性T淋巴细胞的特异性,显著地提高DC的抗原提呈功能,体外能诱导高效而特异的抗癌免疫效应。     

转Survivin基因树突状细胞抗消化道肿瘤的免疫效应研究

目的　研究转染Survivin的树突状细胞 (DC)在体外诱导高效而特异的抗消化道肿瘤免疫效应。方法　用脂质体作为介质 ,将Survivin基因转染入DC ,用Westernblot法检测培养上清Survivin的表达 ,检测这种DC分泌细胞因子白介素 (IL 12 )、肿瘤坏死因子 (TNF) α的功能 ,以及表面分子CD1a、CD83、MHcⅡ、CD80、CD86表达的高低 ,用MTT法诱导人特异的细胞毒性T淋巴细胞 (CTLs)的能力。结果　培养上清中均可以检测到Survivin表达 ;转基因DC的上清IL 12、TNF α两种细胞因子含量为 (2 65 .2± 3 2 .7)ng/L和(4 3 7.1± 83 .5 )ng/L明显比单纯DC组高(P <0 .0 5 ) ;转基因DC表面高表达CD1a、CD83、MHCⅡ、CD80、CD86;转基因的DC提呈的T细胞对胃癌细胞、结肠癌细胞、胆管癌细胞杀伤率分别为 :65 %、77%、85 % ,而未修饰的单纯DC杀伤作用较低。结论　Survivin基因转染修饰的DC能诱导细胞毒性T淋巴细胞的特异性 ,显著地提高DC的抗原提呈功能 ,体外能诱导高效而特异的抗癌免疫效应。     

转染可溶性CD40基因的树突状细胞在体外对T淋巴细胞功能的抑制作用

目的探讨转染可溶性CD40(sCD40)基因的树突状细胞(DC)在体外对T淋巴细胞增殖和细胞毒性T淋巴细胞(CTL)的细胞毒活性的影响。方法采用脂质体转染法,将携带鼠CD40胞外区和绿色荧光蛋白的融合基因的质粒pEGFP-N1/sCD40转染小鼠DC细胞株(DC 2.4)。以Balb/c小鼠淋巴细胞为反应细胞,分别以转染组DC、空载体转染组(空载体组)DC和未行转染处理的DC(空白DC)作为刺激细胞,进行单向混合淋巴细胞培养,四唑氮化合物比色法检测细胞增殖情况。用乳酸脱氢酶释放试验和流式细胞术检测转染组DC及其培养上清液对CTL细胞毒活性及其凋亡的影响。结果转染组DC及其培养上清液对同种细胞刺激的淋巴细胞增殖反应有显著的抑制作用(P<0.05),并对特异性CTL的细胞毒活性具有明显的抑制作用(P<0.05);转染组DC可诱导CTL凋亡(P<0.05)。结论稳定表达sCD40-EGFP融合蛋白的DC,在体外对T淋巴细胞的增殖和CTL的细胞毒活性具有明显的抑制作用,并可诱导CTL凋亡。     

肺癌抗原负载的树突细胞体外诱导细胞毒性T淋巴细胞的杀瘤作用

目的探讨不同方式肺癌抗原负载的树突状细胞(DC)在抗肿瘤免疫中的作用。方法取肺癌患者外周静脉血体外诱导和培养DC,分别以肺癌细胞总RNA转染DC(转染组)、肺癌细胞融合DC(融合组)和肺癌细胞冻融抗原负载DC(冻融组),以未负载抗原的DC(未负载组)和T细胞组作为对照,比较各组(每组n=6)DC诱导的细胞毒性T淋巴细胞(CTL)对肺癌细胞A_(549)的杀伤率(%)。结果转染组、融合组、冻融组、未负载组和T细胞组的杀伤率分别为(73．2±5．9)%、(61．6±6．2)%、(55．3±6．9)%、(22．3±6．1)%和(19．8±6．3)%(P＜0．05)；其中转染组、融合组和冻融组高于未负载组和T细胞组(P＜0．05)；转染组和融合组之间差异无统计学意义(P＞0．05),但两者均大于冻融组(P＜0．05)。RNA转染DC所需的肿瘤细胞数仅是冻融及融合方式的1/5和1/6。结论3种肺癌抗原负载DC方式均有诱导效应细胞杀伤靶细胞的增效作用,而以肺癌细胞总RNA转染方式为佳。     

转染RhoA基因对树突状细胞抗胃癌功能的影响

目的 研究转染RhoA基因对树突状细胞(DC)免疫功能的影响,观察修饰后的DC在体外诱导高效而特异的抗胃癌免疫效应.方法 用增强型绿色荧光蛋白标记的RhoA重组腺病毒载体作为介质,将RhoA基因转染入DC,用RT-PCR法检测培养上清RhoA基因的表达.检测这种DC分泌细胞因子IL-12、TNF-α的功能,以及表面分子CD1α、CD83、MHC-Ⅱ、CD80、CD86的表达,用MTT法诱导人特异的细胞毒性T淋巴细胞的能力. 结果培养上清中均可以检测到RhoA基因表达;在这种转基因DC的上清中IL-12、TNF-α 含量分别为(301±24)和(418±64)pg/ml,明显比非转染的DC组高,P＜0.05;转基因DC表面高表达CD1α(70.13±0.03)、CD83(68.10±0.03)、MHC-Ⅱ(69.73±0.13)、CD80(78.73±0.25)、CD86(74.20±0.05),而在非转染的DC中是低表达的;经转染RhoA基因的DC提呈的T细胞对胃癌细胞的杀伤率为87%,而未修饰的DC杀伤作用较低. 结论RhoA基因转染修饰的DC能诱导细胞毒性T淋巴细胞的特异性,显著地提高DC的抗原提呈功能,在体外能诱导高效而特异的抗胃癌免疫效应.     

胃癌抗原肽Hsp70复合物对转染全长野生型p53的树突状细胞免疫功能的影响

目的 应用联合修饰的树突状细胞(DC)在体外诱导高效而特异的抗胃癌免疫效应。方法 先将全长野生型p53导入脂质体内并转染小鼠骨髓来源的DC,然后用胃癌抗原肽-HSP70复合物等因素修饰已转染全长野生型 p53的 DC(wt-p53 DC),检测这种DC诱导小鼠脾脏淋巴细胞特异的细胞毒性T淋巴细胞(CTLs)的能力,分泌细胞因子功能,以及表面分子表达的高低。结果Western blot检测转染小鼠 p53cDNA的 BMDC及其培养上清中均可以检测到 p53表达;细胞因子含量明显增加(P<0.05),而的其他组的细胞因子含量与对照相比,无显著变化;经流式细胞仪(FACS)检测 wt-p53DC表面高表达 B7-1、B7-2、MCH-Ⅰ、MCH-Ⅱ;脾淋巴细胞经刺激后,能够特异性地杀伤胃癌细胞,杀伤率为91.6％。结论 全长野生型p53基因转染+抗原肽联合修饰DC能诱导小鼠细胞毒性T淋巴细胞的特异性,显著提高DC的抗原提呈功能。     

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.     

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.     

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.     

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.