VEGF基因体外转染大鼠骨髓间充质干细胞的实验研究

目的:探讨脂质体介导血管内皮细胞生长因子(VEGF)基因转染大鼠骨髓间充质干细胞(MSCS)应用于基因治疗的可行性、安全性。方法:体外分离、培养、鉴定MSCs,PcDNA3.1(-)/VEGF165质粒转染MSCs,转染后用免疫荧光和ELISA检测MSCs表达VEGF蛋白的情况,MTT检测MSCs对VEGF质粒转染的敏感性。结果:骨髓中分离得到MSCs,流式细胞检测显示MSCs不表达CD34和CD45,但表达CD90。透射电镜观察可见细胞浆中含大量粗面内质网和分泌颗粒。VEGF基因转染MSCs后第5天抗VEGF免疫荧光染色约90%的MSCs呈阳性,ELISA检测结果显示PcDNA3.1(-)/VEGF165质粒转染组细胞培养上清液中VEGF含量明显高于对照组,并于转染后第5天达到峰值。MTT检测结果显示VEGF质粒转染对MSCs增殖无影响。结论:MSC可作为VEGF基因转染的靶细胞用于基因治疗。     

大黄素诱导人骨髓间充质干细胞向成骨细胞分化的研究

目的:探讨大黄素对人骨髓间充质干细胞向成骨细胞方向分化的影响.方法:体外分离、培养及扩增入骨髓MSCs,用流式细胞仪检测人骨髓MSCs表面抗原的表达,用倒置光学显微镜、透射电镜、四甲基偶氮唑盐比色、碱性磷酸酶染色、碱性磷酸酶活性测定等研究人骨髓MSCs增殖和分化规律.采用不同方法诱导第3代人骨髓MSCs向成骨细胞分化.结果:入骨髓MSCs贴壁生长,呈成纤维细胞外观.流式细胞仪检测显示CD29、CD44表达为阳性,CD34、CD45、HLA-DR表达为阴性.大黄素对入骨髓MSCs增殖的影响:对照组和DXM(地塞米松)组与大黄素 DXM组比较均具有显著差异(P＜0.05).大黄素对人骨髓MSCs分化的影响:对照组和DXM组与大黄素 DXM组比较均具有显著差异(P＜0.01).结论:大黄素能促进入骨髓MSCs向成骨细胞方向分化.     

Wnt3a对骨髓间充质干细胞成软骨分化的影响

[目的]探讨Wnt3a基因对骨髓间充质干细胞(BMSCs)成软骨分化的影响。[方法]分离培养大鼠骨髓间充质干细胞(BMSCs),携带Wnt3a及阴性对照基因(Mock)的慢病毒感染骨髓间充质干细胞,构建过表达Wnt3a骨髓间充质干细胞;采用甲苯胺蓝染色及QPCR观察Wnt3a对骨髓间充质干细胞成软骨分化能力的影响;使用MTT法观察Wnt3a对骨髓间充质干细胞增殖能力的影响。[结果]在0~72 h内,实验组MTT法检测吸光值明显大于对照组(P0.05);BMSCs体外成软骨诱导后,实验组细胞团明显小于对照组,且甲苯胺蓝染色较浅;实验组与对照组比较,成软骨指标Col2A1、Aggrecan和SOX9的m RNA表达降低(P0.05)。[结论]Wnt3a可促进骨髓间充质干细胞增殖,但抑制了骨髓间充质干细胞的成软骨分化。     

rAAV2-hTGF-β1转染犬MSCs诱导分化为软骨细胞的研究

目的 探讨rAAV2-hTGF-β1体外转染犬MSCs定向分化为软骨细胞的可行性.方法 应用密度梯度离心法及贴壁筛选法分离培养犬MSCs,倒置显微镜及Giemsa染色观察细胞形态,流式细胞技术鉴定其表面标记物.取第三代MSCs,分别以感染复数(MOI)为1×105病毒基因数/细胞v.g./cell)、5×105v.g./cell的rAAV2-hTGF-β1进行转染.培养后定期取各组细胞进行相关检测.Western blot检测hTGF-β1的表达,ELISA法测定hTGF-β1的含量,RT-PCR检测Ⅱ型胶原、Aggrecan mRNA的表达,免疫细胞化学法检测Ⅱ型胶原的表达.结果 原代及传代培养的MSCs呈梭形外观,具有较强的增殖能力.细胞表面抗原CD29、CD44、CD105表达阳性,CD34、CD45表达阴性.rAAV2-hTGF-β1转染MSCs后,Western blot法检测到目的 蛋白hTGF-β1稳定表达:ELISA法检测转染组MSCs培养上清液中的hTGF-β1表达,且随时间的延长,各组hTGF-β1浓度逐渐增加,MOI 5×105组表达量明显高于MOI 1×105组(P<0.01);RT-PCR检测到各转染组Ⅱ型胶原、Aggrecan mRNA表达,免疫细胞化学法检测转染组细胞Ⅱ型胶原呈阳性表达,且高MOI值组表达强度明显高于低MOI值组.结论 rAAV2-hTGF-β1转染犬MSCs后可定向分化为软骨细胞,作为软骨组织工程的种子细胞是可行的.     

骨髓基质细胞与关节软骨细胞生物学特性的比较研究

目的观察兔骨髓基质细胞(MSCs)诱导和基因修饰后的主要生物学特性,并与关节软骨细胞进行比较. 方法抽取成年雄性新西兰大白兔髂骨骨髓,密度梯度离心获得骨髓基质细胞,培养传至第5代,按处理方法分为常规培养液组(A组)、条件培养液组(B组)及重组缺陷型腺病毒携带肝细胞生长因子cDNA转染组(C组).条件培养液为常规培养液中含转化生长因子-β1(10 ng/ml)、碱性成纤维细胞生长因子(25 ng/ml)和地塞米松(10-7 mol/L).切取兔膝关节软骨,3 mg/ml Ⅱ型胶原酶消化传代培养至第3代(D组).观察原代MSCs及第5代MSCs(体外培养8～10周后)细胞形态,对第5代MSCs及第3代软骨细胞进行Ⅰ、Ⅱ型胶原免疫组织化学染色,MTT法检测细胞增殖情况.阿利新蓝法检测细胞培养上清液中糖胺多糖(GAG)含量.提取各组培养细胞总RNA,RT-PCR检测Ⅰ、Ⅱ型胶原表达. 结果原代MSCs为短梭形、簇状生长,传代细胞呈长梭形、旋涡样生长.A组细胞爬片Ⅰ型胶原免疫组织化学染色阳性,Ⅱ型胶原免疫组织化学染色阴性,GAG含量低,与D组比较,差异有统计学意义(P＜0.05).B组细胞爬片Ⅰ、Ⅱ型胶原免疫组织化学染色阳性,GAG含量升高,与D组比较差异无统计学意义(P＞0.05);C组转染后第4天增殖率降低,与A组比较差异有统计学意义(P＜0.05),其余时间点各组间无统计学意义(P＞0.05).RT-PCR表明A、B、C组均表达Ⅰ型胶原,B、D组可表达Ⅱ型胶原,C组有较弱的Ⅱ型胶原表达. 结论 MSCs体外培养过程中自然转归趋向于成骨.传代后经向成软骨方向诱导,具有向软骨分化的能力;体外传代培养的MSCs具有干细胞自我增殖和定向分化的特性,可作为靶细胞接受外源目的基因转染并能有效表达.     

人脐血间充质干细胞的分离培养及其多向分化潜能的实验研究

目的 研究人脐血间充质干细胞(MSCs)分离培养的生物学特性及其向成骨、成脂诱导分化的能力.方法 从人脐血中分离扩增MSCs,显微镜下观察其形态及生长情况,绘制生长曲线,电镜下观察超微结构,流式细胞仪检测细胞表面标志物;成骨、成脂诱导后以碱性磷酸酶(ALP)染色、茜素红染色鉴定MSCs成骨分化潜能,油红O染色鉴定成脂分化潜能.结果 人脐血MSCs为成纤维细胞样,漩涡状贴壁生长排列,传至第110代细胞形态无明显变化;电镜下显示为低分化细胞;细胞表面不表达CD34和CD45,强表达CD29、CD44和CD90;成骨诱导后可检测到ALP表达及钙化结节形成;成脂诱导后可检测到脂滴形成.结论 人脐血中可分离出MSCs,与其他来源的MSCs具有类似的生物学特性及多向分化潜能,脐血有可能成为骨组织工程种子细胞的来源.     

大鼠骨髓间充质干细胞的生物学特性和示踪标记

目的 建立大鼠骨髓间充质干细胞(MSCs)的分离和培养方法,观察绿色荧光蛋白(GFP)基因通过慢病毒载体感染MSCs的表达.方法 采用原代贴壁法获得骨髓MSCs,观察细胞形态和生长变化,流式细胞仪鉴定细胞表面标志,体外诱导MSCs向脂肪细胞和成骨细胞分化.采用含有增强型绿色荧光蛋白(EGFP)基因慢病毒载体感染培养的MSCs,比较细胞感染前后生物学特性.结果 原代贴壁筛选结合差异传代培养的MSCs表面标志阳性率分别为CD44 94.81%,CD90 99.53%,CD106 76.34%,MSCs在pH值稳定于7.2～7.4的环境可传20代.体外MSCs诱导分化后特异性染色显示脂质沉淀和骨结节,表达脂肪细胞和成骨细胞特异基因.慢病毒载体可有效感染大鼠MSCs,加入聚凝胺感染效率达到80%,EGFP在MSCs感染后1个月仍持续表达.结论 骨髓MSCs可长期培养,具有良好的多向分化能力.携带EGFP基因慢病毒载体能高效感染MSCs,EGFP可作为MSCs体内研究的示踪标记.     

慢性粒细胞白血病骨髓间充质干细胞的分离及其支持造血的研究

目的探讨慢性粒细胞白血病（CML）患者骨髓间充质干细胞（MSCs）的分离以及体外支持造血的能力。方法采用细胞贴壁法获取16例CML患者的骨髓MSCs，在低血清培养液中培养和扩增。流式细胞仪检测免疫表型。通过油红O染色和Von Kossa染色检测MSCs向脂肪和骨的分化。逆转录聚合酶链法（RTPCR）检测bcr／abl融合基因的表达。对MSCs进行核型分析。RT-PCR检测细胞因子表达情况。将CML患者的骨髓MSCs作为滋养层，应用甲基纤维素半固体培养，检测其支持造血能力。结果CML来源的MSCs在倒置显微镜下为梭形，表达CD29、CD44、CD105，而CD14，CD31、CD34、CD45、HLA-DR均为阴性。在相应的诱导条件下可以向骨和脂肪分化。CML来源的MSCs不表达bcr／abl融合基因，具有正常细胞核型。CML来源的MSCs表达造血相关因子，在体外可以维持和扩增造血干／祖细胞。结论CML患者骨髓中存在具有多向分化能力的MSCs，其具有在体外支持造血的功能。     

大鼠骨髓间充质干细胞诱导分化为表皮细胞的实验观察

目的:研究表皮生长因子(Epidermal growth factor,EGF)加条件培养基体外诱导大鼠 MSCs 向表皮细胞定向分化的可行性。方法:采用 Ficoll-Paque 淋巴细胞分离液分离扩增大鼠骨髓 MSCs,免疫细胞化学染色及流式细胞仪进行鉴定。传至第3代的大鼠 MSCs 用表皮生长因子(EGF)、条件培养基等定向诱导 MSCs 分化为表皮细胞;免疫细胞化学对细胞角蛋白 CK5/8、19(Cytokeratin5/8、19)阳性表达细胞进行检测。结果:从大鼠骨髓中分离培养的 MSCs 增殖能力强,细胞表面标志 CD34、CD45阴性,CD29、CD44阳性,流式细胞仪检测显示细胞纯度高,诱导后7d 细胞免疫化学显示角蛋白5/8、19染色阳性,具有表皮细胞特征。结论:从大鼠骨髓中分离培养出的问充质干细胞,具有自我更新和增殖能力强的特点,经诱导可定向分化表达角蛋白。     

人TGF-β1基因腺病毒载体的构建及对骨髓基质干细胞的定向诱导分化作用

目的构建人转化生长因子β1(TGF-β1)基因腺病毒真核表达载体,并观察感染骨髓基质干细胞(MSCs)后目的基因的表达和对细胞生物学行为的影响。方法以复制缺陷的腺病毒Adeno-X为基因载体,制备携带TGF-β1基因的高滴度腺病毒液感染人MSCs,通过免疫细胞化学、原位杂交、己糖醛酸水平检测及甲苯胺蓝染色等方法鉴定外源基因的表达,分析TGF-β1基因转染对MSCs定向软骨分化的调控机制。结果腺病毒感染MSCs后免疫细胞化学染色证实外源基因编码蛋白的表达,通过原位杂交检测出Ⅱ型胶原蛋白基因mRNA,细胞培养液中己糖醛酸水平明显升高。结论成功构建人TGF-β1基因腺病毒表达载体,证实其在MSCs中的表达和具有向软骨细胞定向分化的诱导作用,为软骨缺损修复的局部基因治疗奠定实验基础。     

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.