5-LOX抑制剂NDGA对人肝癌HepG-2细胞裸鼠移植瘤生长的影响及其机制的探讨

目的观察5-lox抑制剂去甲二氢愈创木酸(NDGA)对裸鼠人肝癌HepG-2细胞移植瘤的作用,并探讨其抗肿瘤的可能机制。方法以人肝癌细胞HepG-2制备裸鼠人肝癌移植瘤模型共18只,将18只荷瘤裸鼠随机分为三组:1、正常对照组(接种正常肝癌HepG2细胞)。2、药物组(接种正常肝癌HepG2细胞同时皮下注入5-lox抑制剂去甲二氢愈创木酸(NDGA),剂量:10μml/L NDGA 0.1ml/10g一天一次,连续5天)。3、溶媒组(接种正常HepG-2细胞后皮下注射溶质二甲亚酚)。密切观察移植瘤生长及裸鼠生存情况21天,记录各组移植瘤肿瘤体积V(V=长径×短径2×0.5),计算衰退率:肿瘤衰退率=1-干预组平均肿瘤体积比/空白对照组平均肿瘤体积比(V/Vo)。通过RT-PCR及Western-blot法检测裸鼠移植瘤组织中bcl-2、caspase3凋亡调节因子以及通路信号蛋白MEK1/2、ERK1/2等的表达。结果实验期间各组荷瘤鼠活动较好,成瘤率100%,且实验过程中无不良繁衍及裸鼠死亡;试验后分别测得各组荷瘤鼠皮下移植瘤体积及肿瘤衰退率,利用单因素方差分析及t检验可以发现:药物组荷瘤鼠较对照组及溶媒组移植瘤体积明显缩小,肿瘤衰退率明显较高,且存在统计学差异(P0.01);利用RT-PCR及Western-blot法检测发现药物组caspase3表达量较对照组及溶媒组明显增强,差异存在统计学意义(P0.01),bcl-2、ERK1/2、MEK1/2等表达量较对照组及溶媒组明显下降,差异具有统计学意义(P0.01)。结论 NDGA对于裸鼠人肝癌移植瘤具有明显的抑制效果。NDGA可能通过诱导肿瘤细胞凋亡而抑制肿瘤生长,其作用机制与抑制MEK/ERK信号通路有关。     

5-LOX siRNA人肝癌HepG2细胞裸鼠瘤模型的建立及意义

目的建立5-脂氧合酶(5-lipoxygenase,5-LOX)5-LOX siRNA转染人肝癌细胞HepG2裸鼠瘤动物模型,探讨iR-NA干扰技术在裸鼠瘤模型中应用的可行性,为肿瘤的实验研究提供平台。方法分别用pRNAT-U6.1-5-LOX siRNA转染的HepG2细胞、空白质粒pRNAT-U6.1转染的HepG2细胞和未转染的HepG2细胞接种裸鼠建立移植瘤模型,分为转染组、转染空载体组和未转染组。建模前,用免疫荧光定量PCR检测转染HepG2细胞5-LOX mRNA表达,成瘤后测量种植瘤体积,并用Western-blot和RT-PCR检测瘤体5-LOX的蛋白和mRNA表达。结果 5-LOX siRNA转染的细胞5-LOX mRNA表达量下降(P<0.01),转染组肿瘤平均体积与转染空载体组及未转染组比较明显减小(P<0.01),而且瘤体5-LOX蛋白及mRNA表达量亦明显下降(P<0.01)。结论 5-LOX siRNA转染肝癌细胞HepG2裸鼠移植瘤瘤实验模型建立成功。将干扰技术和裸鼠移植瘤相结合,为肿瘤的实验研究提供一种更可靠有效的研究方法。     

Establishment of hepatocellular HepG2 cells transfected by 5-LOX siRNA transplanted tumor model .in small nude mice

目的 建立5-脂氧合酶(5 -lipoxygenase,5-LOX)5-LOX siRNA转染人肝癌细胞HepG2裸鼠瘤动物模型,探讨iR-NA干扰技术在裸鼠瘤模型中应用的可行性,为肿瘤的实验研究提供平台.方法 分别用pRNAT-U6.1-5-LOX siRNA转染的HepC2细胞、空白质粒pRNAT-U6.1转染的HepG2细胞和未转染的HepG2细胞接种裸鼠建立移植瘤模型,分为转染组、转染空载体组和未转染组.建模前,用免疫荧光定量PCR检测转染HepG2细胞5-LOX mRNA表达,成瘤后测量种植瘤体积,并用Westem-blot和RT-PCR检测瘤体5-LOX的蛋白和mRNA表达.结果 5-LOX siRNA转染的细胞5-LOX mRNA表达量下降(P＜0.01),转染组肿瘤平均体积与转染空载体组及未转染组比较明显减小(P＜0.01),而且瘤体5-LOX蛋白及mRNA表达量亦明显下降(P＜0.01).结论 5-LOX siRNA转染肝癌细胞HepG2裸鼠移植瘤瘤实验模型建立成功.将干扰技术和裸鼠移植瘤相结合,为肿瘤的实验研究提供一种更可靠有效的研究方法.     

MK886联合塞来昔布对人结肠癌的治疗作用研究

我们以裸鼠为载体,选用环氧化酶-2(COX-2)、5-脂氧合酶(5-LOX)均高表达的人结肠癌HT-29细胞株建立人结肠癌裸鼠皮下移植瘤模型,旨在研究选择性COX-2抑制剂塞来昔布与5-LOX活化蛋白(FLAP)抑制剂MK886的抑瘤效果及其协同作用,并探讨其作用机制[1,2].     

反义局部粘着斑激酶抑制肝癌侵袭生长的研究

目的　观察反义局部粘着斑激酶 (FAK)脱氧寡核苷酸 (ODN)转染对Bel740 2肝癌移植瘤侵袭性生长的影响 ,并探讨其作用机制。方法　以LipofectAMINE介导的反义FAKODN转染Bel 740 2肝癌细胞株后 ,于 6只裸鼠双侧颈背部、髋部共 4处皮下接种 ,观察移植瘤生长情况 ,并行肿瘤微血管密度 (MVD)的免疫组织化学检测及MMP2与TIMP2表达的逆转录 聚合酶链反应(RT PCR)检测。结果　反义FAKODN转染使裸鼠皮下移植瘤的生长受到显著抑制 ,抑瘤率为3 5 .7% ;MVD在反义转染组 ( 9.5 99± 1.2 84)显著低于对照组 [( 13 .915± 2 .618) ,P <0 .0 5 ] ;MMP2表达在反义转染组 ( 0 .199± 0 .0 61)显著低于对照组 ( 0 .42 1± 0 .118) ,TIMP2表达在反义转染组( 0 .461± 0 .15 3 )则显著高于对照组 [( 0 .2 98± 0 .10 4) ,P <0 .0 5 ]。结论　信号转导分子FAK表达阻断可显著抑制Bel 740 2肝癌细胞株在裸鼠体内的侵袭性生长 ,病理性肿瘤血管生成减少及MMP2、TIMP2表达改变与其抗肿瘤作用密切相关。     

靶向IGFIR的siRNA抑制人肝癌裸鼠移植瘤的实验研究

目的:探讨人胰岛素样生长因子1类受体（IGFIR）干扰质粒(PSUPER-siRNA-IGFIR)对人肝癌细胞株SMMC7721裸鼠移植瘤生长的抑制作用。方法:建立人肝癌细胞株SMMC7721裸鼠移植瘤模型，将PSUPER-siRNA-IGFIR质粒转染入移植瘤中，观察对肿瘤生长的作用。结果:PSUPER-siRNA-IGFIR对人肝癌细胞株SMMC7721裸鼠移植瘤有生长抑制作用。与对照组相比IGFIR和MVD的表达明显下降。结论: PSUPER-siRNA-IGFIR能抑制肝癌裸鼠移植瘤的生长。     

NDGA对HepG2细胞5-LOX及其凋亡相关基因表达的影响

目的 探讨脂氧合酶(lipoxygenase)抑制剂NDGA对肝癌细胞HepG2细胞5-LOX及其凋亡相关基因hTERT、bcl-2及bax表达的影响.方法 用RT-PCR方法检测NDGA对HepG2细胞5-LOX及其凋亡相关基因hTERT、bcl-2及bax表达的影响.结果 25、50、100、200 μmol/L的NDGA作用HepG2细胞24、48 h后5-LOX表达逐渐减弱,hTERTmRNA、bcl-2的表达明显下调,而bax的表达逐渐上调.与未加NDGA干预的HepG2对照组比较,P＜0.05.结论 5-LOX在HepG2细胞中存在高表达,提示5-LOX的高表达在肝细胞癌发病过程中可能起着重要作用;而端粒酶hTERTmRNA、bcl-2及bax等凋亡相关基因可能参与了其发病过程.脂氧合酶抑制剂NDGA体外可有效抑制细胞5-LOX的表达,明显下调端粒酶hTERTmRNA、bcl-2及上调bax的表达.LOX可能是肝癌生物化学治疗的新靶点.     

Dpc4基因转染胰腺癌细胞株对裸鼠胰腺癌移植瘤生长的影响

目的 探讨Dpc4基因转染胰腺癌细胞株HS766T对裸鼠移植瘤生长的影响.方法 按pcDNA3,1-Dpc4是否转染人胰腺癌细胞株HS766T将细胞分为pcDNA3.1-Dpc4转染组、pcDNA3.1空载体组和未转染组,RT-PCR鉴定目的基因的表达;将3组细胞分别接种于裸鼠,比较Dpc4基因对裸鼠胰腺癌移植瘤的生长抑制作用,Western blot检测移植瘤中Caspase-3、Bcl-2和Bax的表达.数据以(x)±s表示,组间比较采用方差分析,两两比较采用SNK-q检验.结果 经RT-PCR鉴定,Dpc4基因在pcDNA3.1 -Dpc4中稳定表达.与pcDNA3.1空载体组和未转染组比较,pcDNA3.1-Dpc4转染组胰腺癌细胞HS766T肿瘤体积更小(F=19.43,P＜0.05);pcDNA3,1-Dpc4转染组与pcDNA3.1空载体组的抑瘤率分别为32.3％和4.0％.与pcDNA3.1空载体组比较,pcDNA3.1 -Dpc4转染组Caspase-3和Bax蛋白表达显著升高,而Bcl-2蛋白表达显著降低(F=14.24,13.83,19.50,P＜0.05).结论 Dpc4基因转染可抑制裸鼠胰腺癌移植瘤生长.影响肿瘤细胞的凋亡可能是Dpc4基因抗肿瘤作用之一.     

MBD1 RNA干扰对胰腺癌细胞株BxPC-3生长影响的实验研究

目的 观察阻断MBD1表达后对胰腺癌细胞生长增殖的影响,探讨MBD1在胰腺癌发生发展中的作用.方法 采用RNA干扰技术,构建MBD1-siRNA重组质粒,脂质体介导转染人胰腺癌细胞株BxPC-3,RT-PCR和Western印迹检测转染前后MBD1 mRNA与蛋白的表达变化,MTT法检测转染前后BxPC-3细胞的生长曲线,将细胞接种于裸鼠,观察转染前后胰腺癌细胞体内移植瘤的生长情况.结果 转染siRNA-MBD1质粒后胰腺癌细胞株BxPC-3 MBD1的mRNA与蛋白表达水平明显降低.MTT法检测细胞的生长曲线,发现转染组较转染空质粒组和未转染组生长明显缓慢(P<0.01);体内实验显示,将转染前后的细胞接种于裸鼠,转染组移植瘤生长速度明显较其他两组减慢(P<0.01),RT-PCR检测移植瘤MBD1mRNA表达的变化,转染组中未能测到明显的MBD1表达.而转染组中CDH1、Rb等抑癌基因mRNA的表达明显高于转染空质粒组和未转染组.结论 通过RNA干扰技术,可在转录和翻译水平降低MBD1在胰腺癌细胞株BxPC-3中的表达,并能抑制肿瘤细胞的生长,但其作用机制尚不清楚,MBD1介导的转录抑制作用可能在胰腺癌的发生发展过程中起到重要的作用.     

乐伐替尼对裸鼠皮下人肝癌细胞移植瘤生长及生物钟基因表达水平的影响

目的研究靶向抗肿瘤药物乐伐替尼对裸鼠皮下肝癌移植瘤生长的抑制作用及其对肝癌细胞中生物钟基因表达水平的调控。 方法利用HepG2人肝癌细胞株构建肝癌裸鼠皮下移植瘤模型。12只成瘤裸鼠随机分为处理组（30 mg·kg^-1·d^-1,1次/d）和对照组（DMSO,100 μl·20g^-1·d^-1,1次/d）,每3天测量1次肿瘤体积并绘制移植瘤生长曲线,末次灌胃给药后24 h处死裸鼠并剥离瘤体,比较两组瘤体体积大小及体质量,并采用Real-time PCR法检测肝癌移植瘤组织中生物钟基因BMAL1、CKIε、PER1、PER2、PER3、CRY1、CRY2、CLOCK、NPAS2、REV-Erbα、TIM和DEC2表达水平。 结果两组裸鼠成瘤率为100.0%。与对照组相比,处理组裸鼠一般状态良好,移植瘤生长缓慢,瘤体体积较小,且给药第9天后生长减慢趋势明显（P<0.05）,终末瘤体质量为（0.235±0.43） g,明显小于对照组的（0.633±0.22）g（P=0.006,95%CI=0.167~0.629）;两组裸鼠体质量均随时间的变化而增加,在灌胃给药后第9天时,处理组体质量较对照组大（F=5.194,P=0.034）;处理组裸鼠皮下移植瘤组织中BMAL1、CKIε、PER3和NPAS2 mRNA表达上调,DEC2、PER1、PER2和CRY2 mRNA表达下调,差异有统计学意义（P<0.05）;两组CLOCK、CRY1、REV-Erbα和TIM基因表达水平差异无统计学意义。 结论乐伐替尼可抑制裸鼠皮下肝癌移植瘤的生长,并且可明显上调肝癌组织中的BMAL1、NPAS2、PER3、CKIε基因表达,同时下调PERl、PER2、DEC2基因的表达水平。     

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.