Uroplakin Ⅱ基因在膀胱移行细胞癌中的表达及相关性研究

目的　探讨UroplakinⅡ基因 (UPⅡ )在原发和转移性膀胱移行细胞癌 (TCC)中表达与意义。方法　收集 45例膀胱癌 (其中TCC 3 9例 ,非TCC 6例 )患者的癌组织 ,外周静脉血标本 ,提取总RNA ,行逆转录 聚合酶链反应 (RT PCR ) ,检测UPⅡ基因mRNA的表达。 2 5例其他部位肿瘤及 8例非肿瘤患者组织标本和静脉血作为对照。结果　 45例膀胱肿瘤组织标本中 ,UPⅡ基因在TCC组织中平均阳性率 82 .1% (3 2 /3 9) ,6例非TCC类型膀胱癌 0表达。在T1、T2、T3、T4期膀胱TCC患者组织中UPⅡ基因阳性率分别为 76.5 %、71.4%、90 .9%、10 0 .0 % ;在患者外周血中UPⅡ基因阳性率分别为 5 .9%、14 .2 %、72 .7%、10 0 .0 %。在组织和外周血中低分期 (T1、T2 )与高分期 (T3、T4)TCC表达UPⅡ基因阳性率差异有显著性 (P <0 .0 5 )。其中 4例转移者均阳性 ,接受全身化疗后 3例未再表达。 2 5例其他部位肿瘤组织标本 ,7例肺癌在组织中有 1例阳性表达 ,外周静脉血中 0表达 ;5例肾移行细胞癌在组织中 2例阳性 ,外周静脉血 0表达 ;8例非肿瘤患者组织标本及外周静脉中 0表达。结论　组织及外周血中UPⅡ表达阳性率与肿瘤分期 ,是否转移呈相关性 ;检测TCC患者血中UPⅡ基因可作为监测TCC患者是否转移的指标 ,并可在一定程度上反映化疗疗效 ;     

膀胱移行细胞癌组织中黑色素瘤抗原基因及蛋白的表达

目的探讨膀胱移行细胞癌(TCC)中黑色素瘤抗原(MAGE)基因mRNA的表达及其临床意义。方法采用逆转录聚合酶链反应(RT PCR)技术检测3个膀胱TCC细胞株和20例膀胱TCC患者癌组织(新鲜标本,T1期7例,T2期5例,T3期6例,T4期2例;G11例,G211例,G38例)MAGE A1,A2,A3,A4mRNA表达,免疫组化法检测105例膀胱TCC患者癌组织(石蜡标本,T1期35例,T2期12例,T3期26例,T4期13例,另19例无法确定分期;G113例,G244例,G348例)MAGE A4蛋白的表达。结果3个膀胱TCC细胞株均有MAGE基因mRNA的表达;20例膀胱TCC新鲜标本组织MAGEmRNA阳性:A112例(60%),A216例(80%),A311例(55%),A418例(90%),A1～A4均阳性8例(40%)。105例膀胱TCC石蜡标本组织中MAGE A4蛋白阳性53例(50%),高分级膀胱TCC组织中强表达(++或+++)率为27%(13/48),显著高于低分级的4%(2/57)(F=12.00,P<0.01),高分期膀胱TCC组织中强表达率为27%(14/51),显著高于低分期的0%(0/35)(F=11.48,P<0.01)。结论MAGE基因在膀胱TCC中有较高表达,分级或分期高的膀胱TCC中MACE A4蛋白明显强表达。     

膀胱上皮癌△Np63、p53及ki-67基因表达与预后的相关性研究

目的 探讨△Np63在膀胱移行细胞癌(transitional cell carcinoma of bladder,TCCB)中作用及联合检测△Np63、p53和ki-67与膀胱上皮癌预后的相关性.方法 用免疫组化检测56例膀胱移行细胞癌组织△Np63、p53和ki-67的表达,分析免疫染色结果与病理分级、分期和预后的关系.佶果膀胱移行细胞癌中△Np63、p53和ki-67阳性表达率明显高于正常膀胱黏膜,在高级别、浸润性癌组织中的阳性表达率明显高于低级别、浅表性癌组织,各组阳性表达率差异有统计学意义(P<0.05)△Np63与p53、Ki-67均呈正相关,rs'分别为0.298、0.316,相关性有统计学意义(P<0.05).结论 △Np63可能是TCCB发生和发展的重要促进因素,与膀胱癌的预后密切相关,联合检测△Np63、p53和ki-67可以更好地判断TCCB的预后.     

凋亡抑制基因存活素在膀胱癌中的表达及意义

目的　探讨膀胱癌组织中凋亡抑制基因存活素 (survivin)表达在膀胱癌发生发展中的作用。　方法　应用免疫组化 (SP)法 ,对 6 0例膀胱移行细胞癌组织标本中存活素的表达进行检测。男 4 8例 ,女 12例。平均年龄 5 9岁。病理分级Ⅰ级 16例 ,Ⅱ级 2 4例 ,Ⅲ级 2 0例。临床分期T113例 ,T2 15例 ,T3 2 1例 ,T411例。复发性膀胱癌 2 1例。 10例非肿瘤膀胱组织作对照。　结果　 6 0例膀胱癌组织中存活素阳性表达 36例 (6 0 .0 % ) ,10例非肿瘤膀胱组织存活素表达均为阴性。Ⅰ、Ⅱ、Ⅲ级膀胱癌组织存活素阳性表达率分别为 37.5 % (6 / 16 )、6 6 .7% (16 / 2 4 )、70 .0 % (14 / 2 0 ) ,Ⅰ级与Ⅱ、Ⅲ级比较差异有统计学意义 (P <0 .0 1)。T1、T2 、T3 、T4期膀胱癌组织存活素阳性率分别为 5 3.8% (7/ 13)、6 0 .0 % (9/ 15 )、6 1.9% (13/ 2 1)、6 3.6 % (7/ 11) ,呈逐渐增高趋势 ,但组间两两比较差异均无统计学意义 (P>0 .0 5 )。复发性膀胱癌存活素阳性率为 80 .9% (17/ 2 1)。　结论　存活素与膀胱癌发生发展有关 ,检测膀胱癌组织中存活素表达可能对判断膀胱癌预后有一定意义。     

膀胱移行细胞癌中血管内皮细胞生长因子表达与微血管密度的关系

目的 :探讨膀胱移行细胞癌中血管内皮细胞生长因子 (VEGF)表达与微血管密度 (MVD)的关系。方法 :对 4 3例膀胱移行细胞癌 (TCC)组织及 8例正常膀胱组织的石蜡切片采用免疫组织化学方法检测其VEGF的表达 ,计数微血管数。结果 :正常膀胱组织的VEGF阳性表达率和MVD分别为 0和 1 0 .0± 4 .6。膀胱TCC中G1 +G2 、G3+G4、Ta 1 、T2 +T3+T4的VEGF阳性表达率及MVD分别为 5 9.1 %和 1 7.4± 4 .4、90 .5 %和 2 3 .5±5 .6、5 9.1 %和 1 7.6± 4 .9、90 .5 %和 2 3.3± 5 .5。VEGF表达阳性与阴性组的MVD分别为 2 2 .3± 5 .1和 1 4 .6±4 .2。结论 :VEGF阳性表达率及MVD与膀胱TCC的病理特征有相关性     

低氧诱导因子2和血管内皮生长因子在膀胱癌中的表达及意义

目的　探讨低氧诱导因子 2 (EPAS1/HIF 2α)和血管内皮生长因子 (VEGF)在膀胱移行细胞癌中的表达意义。　方法　应用免疫组织化学技术检测 6 0例膀胱移行细胞癌 [Ⅰ级 2 8例 ,Ⅱ级 12例 ,Ⅲ级 2 0例 ;浅表性膀胱癌 (Tis～T1) 2 9例 ,浸润性 (T2 ～T4) 31例 ]和 8例正常膀胱组织中EPAS1/HIF 2α和VEGF的表达情况 ,χ2 检验分析其表达与膀胱癌分级和分期间的关系。　结果　EPAS1/HIF 2α和VEGF在正常膀胱组织中不表达 ,而在膀胱癌组织表达较强。 6 0例膀胱癌标本中EPAS1/HIF 2α阳性表达 34例 ,阴性 2 6例。病理分级Ⅰ级标本阳性表达 4例 (14 .3% ) ,Ⅱ级 11例 (91.7% ) ,Ⅲ级 19例(95 .0 % )。浅表性癌中阳性 5例 (17.2 % ) ,浸润性癌中阳性 2 9例 (93.5 % )。EPAS1/HIF 2α与肿瘤的病理分级 (r =0 .86 2 ,P <0 .0 0 1)和临床分期 (r=0 .80 5 ,P <0 .0 0 1)密切相关。 6 0例膀胱癌标本中VEGF阳性表达 4 4例。病理分级Ⅰ级标本阳性表达 12例 (42 .8% ) ,Ⅱ级 12例、Ⅲ级 19例均阳性表达。浅表性膀胱癌中阳性表达 14例 (48.3% ) ,浸润性癌中阳性表达 30例 (96 .8% ) ,VEGF表达与肿瘤病理分级 (r=0 .84 1,P <0 .0 0 1)和临床分期 (r =0 .819,P <0 .0 0 1)密切相关。EPAS1/HIF 2α表达与VEGF表达密切相关 (r=     

膀胱部分切除术的价值

膀胱癌是泌尿系统最常见的恶性肿瘤,在我国其发病率居泌尿系统恶性肿瘤的首位.其中膀胱移行细胞癌(TCC)最为常见,占膀胱癌的90％以上.膀胱鳞状细胞癌比较少见,占膀胱癌的3％ ～7％.膀胱腺癌更为少见,占膀胱癌的比例＜2％.膀胱移行细胞癌的治疗方法取决于肿瘤的分期和细胞分级.表浅性肿瘤(SBC)占全部膀胱肿瘤的75％～85％,包括Tis、T0、T,期膀胱肿瘤,常采用保留膀胱手术方式;浸润性膀胱肿瘤是指肿瘤浸润肌层T2、T3、T4期肿瘤,其基本治疗是根治性膀胱切除术[1].     

生长抑制基因p33INGl在膀胱移行细胞癌中的表达及意义

目的探讨膀胱移行细胞癌（TCC）组织中生长抑制基因p33ING1表达的意义.方法采用免疫组织化学方法,对68例膀胱TCC组织标本中p33ING1表达进行检测.男58例,女10例.平均年龄65岁.病理分级Ⅰ级16例,Ⅱ级22例,Ⅲ级30例.临床分期T125例、T217例、T314例、T412.例.复发性膀胱癌47例.12例正常膀胱组织作对照.结果 12例正常膀胱黏膜组织中p33ING1均为强阳性.68例TCC标本中,p33ING1表达阳性23例,阳性率为33.8%.p33ING表达与膀胱TCC病理分级、临床分期以及复发密切相关（P＜0.05）.结论 p33ING1在膀胱TCC组织中存在表达缺失,其表达缺失程度与肿瘤病理分级、临床分期及复发相关,可作为观察膀胱TCC复发指标之一.     

上皮钙粘蛋白/连接素复合体在膀胱癌中表达及对预后的判断价值

目的 :探讨上皮钙粘蛋白 /连接素 (E cd/cat)复合体在膀胱癌中的表达及对判断膀胱癌的复发及预后的价值。方法 :应用免疫组织化学法 (SP法 )检测 72例膀胱移行细胞癌和 10例正常泌尿系移行上皮石蜡包埋标本中E cd/cat复合体的表达情况。结果 :10例正常泌尿系移行上皮E cd/cat复合体各组成成分均正常表达。膀胱移行细胞癌中E cd、α cat、β cat、γ cat异常表达率分别为5 6 .9% (4 1/ 72 )、4 4 .4 % (32 / 72 )、5 6 .9% (4 1/ 72 )、4 3.1% (31/ 72 )。E cd和cat表达具有显著相关性 (P<0 .0 1)。E cd/cat复合体异常表达率与膀胱癌的病理分级和临床分期密切相关 (P <0 .0 5 )。β cat的异常表达与所有肿瘤的复发相关 (P <0 .0 5 )。α cat异常表达与表浅肿瘤 (Tis～T1期 )的复发密切相关 (P <0 .0 1)。γ cat异常表达与肿瘤的生存预后密切相关 (P <0 .0 1)。结论 :E cd/cat复合体的异常表达与膀胱癌的分化和侵袭程度密切相关。β cat是膀胱肿瘤复发预后的较好指标。α cat是表浅肿瘤复发预后的较好指标。γ cat是膀胱癌生存预后的有价值指标。     

p53,CD34,E-钙粘蛋白在膀胱癌中的表达及判断预后的价值

目的　探讨 p5 3、CD3 4 、E 钙粘蛋白 (E cadherin)在膀胱移行细胞癌中的表达及判断膀胱癌预后的价值。　方法　采用免疫组化方法检测 4 6例膀胱移行细胞癌和 8例正常膀胱粘膜标本p5 3、CD3 4 、E cadherin的表达情况。　结果　 4 6例膀胱癌标本中p5 3、E cadherin的异常表达率分别为2 1.7%和 4 5 .6 %。p5 3异常表达在表浅型膀胱癌为 9.1% ,浸润型为 33.3% ,差别有显著性意义 (P <0 .0 5 ) ;病理Ⅰ～Ⅱ级异常表达 7.1% ,Ⅲ级 4 4 .4 % ,差别有显著性意义 (P <0 .0 0 5 ) ;复发组异常表达89 % ,未复发组 15 % ,差别有显著性意义 (P <0 .0 0 5 )。E Cadherin的异常表达率在浅表型膀胱癌为77.3% ,浸润型为 33.3% ,差别有显著性意义 (P <0 .0 0 5 ) ;在Ⅰ、Ⅱ级膀胱癌为 71.4 % ,Ⅲ级为2 7.8% ,差别有显著性意义 (P <0 .0 0 5 ) ;在复发组与未复发组分别为 18.0 %和 6 1.0 % ,差别有显著性意义 (P <0 .0 1)。CD3 4 在膀胱癌中的异常表达率为 4 1.3% ,在不同分期分级及复发与未复发组之间的表达差别均无显著性意义。　结论　p5 3和E Cadherin的异常表达与膀胱癌的恶性程度及复发密切相关 ,可作为判定肿瘤预后和复发的分子生物学指标     

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.     

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.     

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.