MAGE-3抗原肽体外诱导肝癌患者免疫应答的研究

目的：利用载有MAGE－3抗原肽的树突状细胞（DC）活化原发性肝细胞癌（HCC）患者T淋巴细胞，探讨是否可以体外诱导特异性细胞毒T细胞细胞（CTL）应答。方法：通过逆转录多聚酶链反应和测序分析MAGE－3多肽表位密集区的核苷酸变异状况，体外培养HLA－A2表型的HCC患者及正常献血员外周血来源DC，并经孵育携带MAGE－3／HLA－A2抗原肽FLWG－PRALV，用以活化T淋巴细胞，利用特异性杀伤实验检测CTL应答。结果：中国HCC患者表达的MAGE－3序列高度保守。用特定细胞因子和无血清培养基可成功培养HCC患者外周血精源的DC。经多肽冲击的DC诱导，3例HCC例者和3例正常献血员可成功培养HCC患者外周血来源的DC。经多肽冲击的DC诱导，3例HCC患者的3例正常献血员中各有2例产生CTL免疫应答。结论：载有MAGE－3抗原肽的DC可以体外诱导特异性的CTL免疫应答。提示HLA－A2限制性的MAGE－3抗原肽经DC递呈可以作为有潜力的肝癌免疫治疗疫苗。     

应用CT抗原肽诱导肝癌患者特异性细胞毒反应的研究

目的 研究应用不同肿瘤睾丸抗原（CTA）多肽诱导肝细胞肝癌（HCC）患者特异性细胞毒反应的情况。方法 RT-PCR方法检测一例HLA-A2阳性表达的HCC患者肝癌组织中三种CT抗原（MAGE-1，MAGE-3和NY-ESO-1）基因mRNA的表达情况，用免疫磁珠从该患者外周血单个核细胞（PBMC）中分离出CD8 T细胞作为效应细胞；将其余自体CD8-PBMC分别与三种CT抗原肽共孵育，经γ-射线照射后作为抗原呈递细胞（APC），分别与CD8 效应细胞进行混合淋巴细胞培养。7天后同法再刺激患者的CD8 T细胞1次，诱导形成细胞毒T淋巴细胞CTL），同时了以相同的CD8 效应细胞，加入IL-2培养作为对照组。培养两周后将三种CT抗原肽刺激的效应细胞，分别与带有相应抗原肽的T2靶细胞共孵育来检测杀伤效应。效应细胞，靶细胞（E：T）为10：1；用IFN-γ细胞因子分泌检测法，通过流式细胞仪检测产生IFN-γ的效应CD8 T细胞的频数来反映杀伤活性。结果 该患者MAGE-3和NY-ESO-1表达阳性，MAGE-1表达阴性，培养第14天，效应细胞共增加至原细胞数的4倍，NY-ESO-1抗原肽刺激的效应细胞对靶细胞（T2细胞 NY-ESO-1抗原肽0杀伤活性为10.0%;MAGE-3抗原肽刺激的效应细胞对靶细胞（T2细胞MAGE-3抗原肽）杀伤活性为8.5%;MAGE-1抗原肽刺激的效应细胞对靶细胞（T2细胞 MAGE-1抗原肽）杀伤活性为3.2%。结论 本实验结果表明，应用HCC患者阳性表达的CT抗原肽，可以诱导出该患者特异的细胞毒性T淋巴细胞，其杀伤活性较之无抗原肽和阴性抗原肽刺激明显增强。     

应用MAGE-1抗原肽体外诱导特异性细胞毒T淋巴细胞形成

目的：探讨应用MAGE－1抗原肽治疗肝细胞肝癌（HCC）的可行性。方法：接受MAGE－1抗原九肽NYKCRFPEI孵育的外周血单个核细胞（PBMC）经3000rad的射线照射后用作抗原呈递细胞（APC），每隔7d刺激HCC病人自体的PBMC 1次，进行混合淋巴细胞培养（MLCs)，共4次后作为细胞毒T淋巴细胞（CTL），应用乳酸脱氢酶（LDH）释放分析法检测CTL对靶细胞的杀伤效应。结果；从培养的第1周至第4周，淋巴细胞共增加至原细胞数的32倍；在效应细胞；靶细胞（E：T）为10：1时，CTL对MAGE－1抗原九肽NYKCRFPEI孵育的自体淋巴母细胞的杀伤效应为62．5％，对MAGE－1阳性，HLA－A24阳性的HCC细胞株BEL7405的杀伤效应为40．2％，两者均明显高于自体淋巴母细胞的杀伤效应（17．9％）。和对MAGE－1阳性，HLA－A24阴性的HCC细胞株HLE的杀伤效应（19．6％），及对MAGE－1阴性，HLA－A24阴性的HCC细胞株QGY 7701的杀伤效应（1．6％）；在E：T为3．3：1时，CTL对肽孵育的自体淋巴母细胞的杀伤效应为53．6％，明显高于自体淋巴母细胞的杀伤效应（15．6％），对HLE的杀伤效应（13％）和对QGY7701的杀伤效应（1％）。结论：本实验结果表明，应用MAGE－1抗原肽NYKCRFPEI，能在体外从HCC病人的PBMC中有效地诱导出具有特异性杀伤能力的CTL。     

黑色素瘤抗原基因在肝癌细胞系中的表达

目的：研究黑色素瘤抗原（MAGE）基因在肝癌（HCC）细胞系中的表达，为应用MAGE抗原肽作为疫苗治疗肝癌的体外实验筛选靶细胞。方法：分别用逆转录-聚合酶链反应（RT-PCR）和免疫组织化学方法对MAGE-1和MAGE-3mRNA及MAGE-1蛋白在8种HCC细胞系中的表达进行检测，用微量淋巴细胞毒法测定HCC细胞系的主要组织相容性复合物（MHC)I类分子的表达。结果：6种HCC细胞系MAGE-1基因mRNA阳性表达，2种MAGE-3阳性；有5种细胞系MAGE-1基因蛋白阳性。BEL7405HLA-A24阳性，HLE和HpG2HLA-A2阳性。结论：MAGE基因在HCC细胞系中有较高的表达率，HLE和BEL7405可作为阳性靶细胞，其他细胞系可作为相应的对照细胞，应用于用MAGE抗原肽疫苗治疗HCC的体外实验研究中。     

恶性黑色素瘤抗原基因与胃肠肿瘤

人类恶性黑色素瘤细胞携带有可以被特异性的细胞毒T淋巴细胞(cytoxicTlymphocytes,CTL)所识别的抗原。恶性黑色素瘤抗原基因(melanomaantigensgene,MAGE)家族包含17个成员,除睾丸和胎盘外,几乎仅限于肿瘤组织中表达。与MAGE-1基因一样,MAGE-3基因编码的肿瘤抗原亦将人类白细胞抗原(HLA)-A1作为存在的前提犤1犦。此基因在黑色素瘤中的表达率高于MAGE-1,并且可以于多种组织来源肿瘤中表达。由MAGE编码的抗原具有严格的肿瘤特异性,MAGE基因在消化道肿瘤特异性和广泛表达使得MAGE肽疫苗治疗消化道肿瘤成为可能。一、MAGE与食管…     

MAGE-1抗原肽致敏DC活化淋巴细胞对裸鼠肝癌移植瘤的免疫防护作用

目的　观察黑色素瘤 1基因 (MAGE 1)抗原肽致敏树突状细胞 (DC)所活化的淋巴细胞(CTL)对人肝癌HCC移植瘤的抑制和消退作用 ,评估临床治疗HCC的可行性和有效性。　方法BEL 74 0 2HCC细胞于 30只裸鼠背部皮下接种 ,建立裸鼠HCC移植瘤模型 ,其中 2 2只成瘤 ;用MAGE 1九肽致敏DC所活化的淋巴细胞 (1× 10 6)注入肿瘤部位皮下 (治疗组A ,n =5 ) ,其余 17只随机分成 5组 (B、C、D、E、F) ,用其他不同性质的细胞治疗 ,观察各组肿瘤生长情况并进行病理学分析和统计学处理 ,阐明特异性CTL对肿瘤的作用机制。　结果　 (1)A组HCC移植瘤均停止生长并趋于缩小 ,荷瘤裸鼠观察期内无死亡 ;而其他 5组肿瘤均快速生长 ,大部分荷瘤裸鼠 2周内死亡。MAGE 1九肽致敏DC所活化淋巴细胞能显著抑制HCC移植瘤生长 ,促使肿瘤消退 (P <0 0 1)。 (2 )A组移植肿瘤广泛坏死 ,肿瘤细胞广泛凋亡。　结论　MAGE 1九肽致敏DC有抑制HCC生长 ,促进HCC消退 ,防止肿瘤转移、复发的作用。肿瘤细胞凋亡增强是DC肿瘤免疫的可能机制。MAGE 1九肽联合DC可作为治疗HCC的新型疫苗。     

肾细胞癌及尿路移行细胞癌组织中黑色素瘤抗原基因mRNA的表达

目的　评价肿瘤特异性黑色素瘤抗原 (MAGE) 1、 3基因作为肾细胞癌及尿路移行细胞癌组织中的免疫学检测和免疫治疗、基因治疗分子标志物的可行性。　方法　肾细胞癌组织标本 18例 ,尿路移行细胞癌组织标本 2 6例 ,相应的癌旁组织 10例 ,采用RT PCR方法对MAGE 1、MAGE 3基因进行测定。　结果　 18例肾癌组织中MAGE 1mRNA阳性表达 10例 (5 6 % ) ,MAGE 3mRNA阳性表达11例 (6 1% ) ,MAGE 1及MAGE 3同时表达 8例 (44 % ) ;2 6例尿路移行细胞癌组织中MAGE 1mRNA阳性表达 16例 (6 2 % ) ,MAGE 3mRNA阳性表达 15例 (5 8% ) ,MAGE 1及MAGE 3同时表达 12例 (46 % )。癌旁组织 10例均不表达MAGE 1及MAGE 3。　结论　MAGE 1、MAGE 3基因有可能作为肾癌及尿路移行细胞癌组织免疫学检测的分子标志物 ,并且具有作为免疫治疗、基因治疗特异性靶位的潜在价值。     

肿瘤增殖细胞核抗原的人白细胞抗原-A2限制性细胞毒T淋巴细胞表位鉴定

目的 鉴定肿瘤增殖细胞核抗原(PCNA)的人白细胞抗原(HLA)-A2限制性细胞毒T淋巴细胞(CTL)表位,为肿瘤疫苗制备提供依据.方法 根据PCNACTL表位评分结果,合成8条候选肽;采用经典T2-肽结合实验检测候选肽与HLA-A2分子亲和力;采用酶联免疫斑点法(ELISPOT)检测候选肽刺激的HLA-A2阳性CTL分泌干扰素(IFN)-γ能力.结果 T2-肽结合实验结果显示PCNA 14-22、110-118位置候选肽与HLA-A2分子结合力较强,其荧光系数FI值最高,分别为0.30和0.34,显著高于其他候选肽.ELISPOT检测结果显示14-22和39-47位置候选肽形成的IFN-γ斑点数目(477.25±52.08、640.50±145.74)明显高于阴性对照(0.75±0.50)及其余候选肽.结论 PCNA抗原14-22位置候选肽KVLEALKDL可作为HLA-A2限制性CTL表位用于制备肿瘤疫苗.     

肿瘤睾丸抗原CT10基因mRNA在肝细胞肝癌中的表达及HLA-A2限制性CTL表位的预测

目的检测CT10基因mRNA在肝细胞肝癌 (HCC)中的表达情况 ,了解肿瘤睾丸抗原CT10基因mRNA在HCC中的表达是否具有肿瘤特异性 ;对CT10HLA A2限制性CTL表位进行预测。方法用逆转录 聚合酶链反应 (RT PCR)方法对 45例HCC患者癌组织和相应癌旁组织的CT10基因mRNA表达情况进行了检测 ,对其中 3例RT PCR扩增产物的目的片段进行DNA序列测定 ;利用超基序法和量化基序法联合预测CT10HLA A2限制性CTL表位。结果 45例HCC患者中 ,19例表达CT10mRNA ,阳性率为 42 % ,相应的癌旁组织中结果均显示阴性 ;3例DNA测序结果表明RT PCR产物确为CT10cDNA。CT10的表达与年龄、性别、肿瘤体积、分化程度、血清甲胎球蛋白 (AFP)水平、HBV和HCV感染无显著相关性 (P >0 0 5 ) ;预测发现 9个HLA A2限制性CTL表位。结论CT10在HCC中呈高比例、特异性表达 ,可望成为HCC免疫治疗的理想靶位。     

脂质体介导IFN-γ基因治疗荷大肠癌小鼠的实验研究

目的探讨利用γ 干扰素 (interferon γ ,IFN γ)基因对大肠癌的治疗作用及其作用机制。方法构建携带IFN γ基因的真核表达质粒pcDNA3 IFN γ ,以脂质体作载体 ,对荷大肠癌小鼠行瘤体内注射IFN γ基因 ,检测经基因治疗后小鼠体内IFN γ基因的表达、脾脏的细胞毒性T淋巴细胞 (cyto toxicTlymphoctye,CTL)活性、肿瘤的大小、肿瘤局部的淋巴细胞浸润情况及荷瘤小鼠的生存期。结果经IFN γ基因治疗后 ,治疗组小鼠血清中IFN γ表达量和脾脏的CTL活性明显增强 (P <0 0 1) ,肿瘤局部淋巴细胞浸润明显 ,肿瘤生长受到抑制 ,荷瘤小鼠的存活期明显延长。结论利用IFN γ基因治疗大肠癌具有明显的疗效。     

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.