反义寡核苷酸抑制Survivin基因表达对移植静脉内膜增生的影响

目的研究反义寡脱氧核苷酸（ASODN）抑制Survivin基因表达对移植静脉内膜增生的抑制作用。方法Wistar大鼠60只，建立自体静脉移植模型，术后随机分为：对照组、Survivin ASODN 50、200μg组、正义对照组、Lipofectin＋pluronic等五个组，施加不同的处理因素，在移植后1、2周取材。组织形态学方法比较内膜增生程度，逆转录．聚合酶链反应（RT-PCR）检测Survivin基因的mRNA表达，Westem blot检测Survivin基因的蛋白产物表达，免疫组织化学方法检测Survivin及增殖细胞核抗原（PCNA）的表达，脱氧核苷酸转移酶末端标记法（TUNEL）检测血管平滑肌细胞（VSMC）凋亡的变化。结果移植后1、2周内膜增生明显，局部转染50μg Survivin ASODN组内膜增生明显受抑制（P〈0．05），200μg组受抑制程度更为明显（P〈0．05）；与对照组相比，Survivln ASODN组Survivin的mRNA及蛋白产物表达显著减少（P〈0．05），PCNA阳性表达同时减少，而TUNEL阳性细胞却明显增加。结论Survivin ASODN可显著抑制移植静脉的内膜增生，其作用可能是通过抑制Survivin基因及其蛋白产物表达，从而抑制VSMC增殖、促进其凋亡而实现的。     

转染survivin反义寡脱氧核苷酸对移植血管内膜增生的影响

目的研究survivin基因的反义寡脱氧核苷酸（ASODN）对移植血管内膜增生的影响。方法Wistar大鼠60只，建立自体静脉移植模型，术后随机分为5组：对照组，survivin ASODN 50μg组，200μg组，正义对照组，lipoectin＋pluronic组。分别施加不同的处理因素，在移植后1，2周取材。用组织形态学方法比较内膜增生程度；用半定量RT-PCR检测survivin基因的mRNA表达；Western blot检测survivin基因的蛋白产物表达；免疫组化方法检测survivin及增殖细胞核抗原（PCNA）的表达，TUNEL法检测血管平滑肌细胞（VSMC）凋亡。结果静脉移植1～2周内膜增生明显，局部转染50μg survivin ASODN后明显抑制内膜增生（P〈0．05），200μg组受抑制程度较50μg组更为显著（P〈0．05）。静脉移植后，对照组survivin的mRNA及蛋白产物表达显著增加，而survivin ASODN组却显著减少（P〈0．05），VSMC中PCNA表达也同时减少，而TUNEL阳性细胞明显增加。结论survivin ASODNs可显著抑制移植静脉的内膜增生；其作用可能是通过抑制survivin的基因及蛋白产物表达，促进VSMC凋亡而实现的。     

早期应答基因产物表达对移植静脉平滑肌细胞增殖的影响

目的　探讨c fos、c jun、c myc等早期应答基因与移植静脉平滑肌细胞 (SMC)增殖的影响。方法　建立Wistar大鼠 (6 0只 )自体血管移植模型 ,移植后 2h、6h、2d、1周、2周、4周分别切取移植静脉 ,应用免疫组织化学方法动态观察早期应答基因的变化情况。结果　正常血管平滑肌细胞中鲜有早期应答基因表达 ,c fos、c jun于移植后 2h达高峰 ,吻合口处为 (13.1± 3.3) %、(12 .8±2 .9) % ,中段静脉为 (10 .3± 2 .8) %、(10 .0± 1.9) % ,与术后 1周相比差异有显著性 (P <0 .0 1) ;c myc于 2h有少量表达 ,于 1周时达高峰 [吻合口 (16 .2± 3.8) %、中段静脉 (11.2± 2 .3) % ],与术后 4周相比差异有显著性 (P <0 .0 1)。结论　在移植静脉中 ,早期应答基因是SMC增殖的早期反应基因 ,参与DNA复制 ;c myc可能参与了细胞的持续增殖。     

可溶性支架转染c-myc基因反义寡核苷酸对静脉移植物c-myc及PCNA表达的影响

目的采用可溶性支架将原癌基因c—myc反义寡核苷酸转染静脉移植物，观察其对静脉移植物内c—myc蛋白和增殖细胞核抗原（PCNA）蛋白产物表达的影响。方法50只新西兰大耳白兔建立兔颈外静脉颈总动脉旁路移植模型后随机分成5组，每组10只。对照组：无支架；组1：植入单纯可溶性支架；组2：植入正义c—myc寡核苷酸可溶性支架；组3：植入反义c—myc寡核苷酸可溶性支架；组4：植入不匹配c—myc寡核苷酸可溶性支架。于静脉移植后7d、28d和90d取出静脉移植物，采用免疫组织化学方法检测其c—myc蛋白和PCNA蛋白的表达。结果对照组、组1、组2、组4静脉移植术后7d、28d、90d时静脉移植物内膜和中膜内可见大量c—myc蛋白和PCNA蛋白表达阳性的细胞，与同时间点组3比较差别均有统计学意义（P〈0．01）。28d、90d时5组静脉移植物内c—myc蛋白的表达与同组7d时比较明显增强（P〈0．01）。结论可溶性支架转染c—myc反义寡核苷酸可显著抑制静脉移植物内c—myc蛋白和PCNA蛋白的表达。     

经外膜缓释雷公藤内酯醇抑制自体移植静脉内膜增生

目的:探讨经外膜缓释雷公藤内酯醇（triptolide）对自体移植静脉内膜增生的抑制作用。方法:健康雄性新西兰大白兔24只，建立颈外静脉-颈总动脉移植模型。随机将动物等分为3组。空白组移植血管不给任何处理， F-127多聚凝胶对照组在移植血管外膜喷洒20 %F-127多聚凝胶0.5 mL，实验组在移植血管外膜喷洒携带雷公藤内酯醇300μg的F-127多聚凝胶0.5 mL。术后2周取标本。用组织形态学方法检测血管内膜增生程度，免疫组化检测标本中bcl-2和Fas的表达，TUNEL法检测标本中血管平滑肌细胞(VSMC)凋亡的水平。结果:静脉移植2周后，与空白组和F-127对照组比较，实验组血管内膜增生明显受抑制（P<0.05），bcl-2的表达［（18.2±8.4） %］显著减少，而Fas的表达［（21.4±8.9） %］显著增加，凋亡细胞［（28.4±7.6） %］也显著增加（P<0.05）。结论:经外膜缓释雷公藤内酯醇可有效抑制移植静脉内膜增生，这一作用可能系通过促进VSMC凋亡而实现的。     

反义寡核苷酸对血管平滑肌细胞c-myc、增殖细胞核抗原蛋白表达的影响

目的　研究反义c myc、增殖细胞核抗原 (PCNA)基因片断对血管平滑肌细胞 (VSMCs)增殖的作用。　方法　使正义、反义及错配反义c myc、PCNA ,分别作用于体外培养的VSMCs ,应用蛋白印迹和免疫组化法测定并经计算机图像分析 ,观察其对c myc、PCNA蛋白表达的影响。　结果　 10μmol/L浓度的反义c myc、PCNA作用于VSMCs后 1～ 5d ,相应c myc和PCNA蛋白表达减弱 ,计算机图像分析表明其表达产物与对照组相比 ,差异有显著意义 (P <0 0 5 ) ,而正义和错配反义寡核苷酸无此效应 (P >0 0 5 )。　结论　反义c myc、PCNA寡核苷酸可通过阻遏其相应基因表达进而抑制蛋白表达及VSMCs增殖。     

细胞间粘附分子-1在自体移植静脉中表达的动态变化

目的　研究细胞间粘附分子 (ICAM ) 1在自体移植静脉中表达的动态变化规律 ,探讨其与内膜增生的关系及意义。方法　Wistar大鼠 5 6只 ,建立自体静脉移植模型 ,随机分为 7组 ,分别在移植后 1、3d ,1、2、4、6、8周切取移植静脉。半定量逆转录 聚合酶链反应 (RT PCR)结合原位杂交定位研究移植血管中ICAM 1mRNA的表达 ,Westernblot联合免疫组织化学方法检测I CAM 1蛋白产物表达的变化。结果　ICAM 1mRNART PCR扩增见静脉移植 1～ 3d即出现表达增强 ,1～ 2周达到高峰 ,表达值分别为 ( 3 6.6± 12 .9) %和 ( 5 8.7± 11.1) % ,与其他组比较差异有显著性 (P <0 .0 1) ,6～ 8周逐渐恢复正常 ,与原位杂交变化趋势基本一致。免疫组织化学结果见I CAM 1在移植 1～ 7d表达明显增多 ,2～ 4周达到高峰 ,分别为 ( 2 3 .5± 7.1) %和 ( 2 0 .6± 9.2 ) % ,与其他组比较差异有显著性 (P <0 .0 1) ,8周恢复至正常水平 ,与Western蛋白印迹结果一致。结论ICAM 1与移植静脉内膜增生关系密切 ,可能成为防治内膜增生以及血管移植后狭窄闭塞一个新的治疗靶点。     

血管外支架预防猪大隐静脉桥再狭窄的实验研究

目的以猪大隐静脉—颈总动脉间置动物模型为基础,观察涤纶血管外支架支持预防静脉桥血管内、中膜增生的作用。方法20~25kg普通长白猪10只,行双侧大隐静脉—颈总动脉端端吻合,实验侧静脉桥放置涤纶外支架。术后28d取出桥血管,组织学和免疫组化检测。结果静脉桥血管内膜增生对照组(0·4269±0·0794)mm,实验组(0·1371±0·0390)mm(P<0·01);中膜增生对照组(0·4601±0·0628)mm,实验组(0·2590±0·0178)mm(P<0·01);对照组内膜面积是实验组的2·5倍,中膜面积是实验组的近2倍;实验组内膜及中膜内侧区域PCNA、PDGF阳性细胞显著减少,PCNA从(13·2±2·17)%减少至(2·34±0·68)%(P<0·01),PDGF从(13·10±1·39)%减少至(2·44±0·25)%(P<0·01)。结论非限制性涤纶血管外支架可以显著抑制大隐静脉桥血管新内膜及中膜增生,可能预防大隐静脉桥的再狭窄。     

反义寡核苷酸抑制早期生长反应基因1表达对移植静脉内膜增生的影响

目的 研究反义寡脱氧核苷酸(antisense oligodeoxynucleotides,ASODN)抑制早期生长反应基因1(early growth response gene-1,Egr-1)表达对移植静脉血管平滑肌细胞增殖和内膜增生的影响.方法构建Egr-1 ASODN,建立自体静脉移植模型,Egr-1 ASODN转染移植静脉,术后随机分为1、2、6、24 h,3、7、14、28、42 d组,以未应用Egr-1 ASODN的大鼠为对照组.荧光显微镜检测Egr-1 ASODN转染移植静脉情况;应用原位杂交和RT-PCR方法检测Egr-1 mRNA的表达;联合应用免疫组织化学方法和Western blot检测Egr-1蛋白表达情况.结果 实验组移植1 h,Egr-1 ASODN主要位于移植静脉的外膜、中膜和部分内皮细胞(荧光灰度值为67±11),移植2 h至24 h,Egr-1 ASODN则主要位于移植静脉的中膜,移植7 d,Egr-1 ASODN主要位于移植静脉的内膜.移植后期未检测到Egr-1 ASODN的表达.Egr-1 mRNA的表达只呈现一个高峰(基因表达值1.8±0.5).移植早期Egr-1蛋白表达主要位于中膜的VSMC、部分单核细胞和内皮细胞,而移植后期在中膜和新生内膜的VSMC都未检测到Egr-1蛋白的表达.与对照组相比VSMC的增殖程度和内膜厚度均明显减轻(P＜0.01).结论 Egr-1 ASODN可显著抑制移植静脉的内膜增生,其作用可能是通过抑制Egr-1基因及其蛋白产物表达,从而抑制VSMC增殖、促进其凋亡而实现的.     

ET 1，cmy c在自体静脉移植血管内膜增殖表达意义

为观察内皮素、cmy c在自体移植静脉术后内膜增生中的相互作用，探讨移植静脉术后再狭窄的机制。笔者应用免疫组化技术观察内皮素、cmy c在自体移植静脉术后内膜增生中的表达。结果表明移植静脉术后早期，内皮素1（ET 1）在平滑肌细胞出现阳性表达，术后1周开始增多，到术后2周达高峰，4周开始减少，而cmy c亦在同时期表达，1周后逐渐呈高表达，在移植静脉术后2周后表达逐渐减少，二者与增殖细胞核抗原（PCNA）表达呈一致性改变。ET 1，cmy c术后1~2周表达与早期表达有显著差异（P<0.05 ),ET 1与cmy c呈正相关（r=0.36）。提示在血管移植术后ET 1与cmy c之间存在调控作用，即ET 1可以激活cmy c,使静止期SMC进入增殖期,产生血管平滑肌细胞（SMC）过度增殖,同时表明ET 1可能是cmy c等早期应答基因持续增殖一个重要原因，这也为今后应用ET 1抑制剂加反义cmy c抑制内膜增殖提供了一定的理论依据。     

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.