细胞核Snail因子在胰腺癌上皮-间质转化中的作用

目的：探讨细胞核因子Snail在胰腺癌组织中的表达及与胰腺癌上皮-间质转化（EMT）过程的相关性。 方法：采用免疫组织化学方法检测77例胰腺癌组织（研究组）与13例正常胰腺组织（对照组）中的Snail、Slug、E-cadherin、vimentin的表达。 结果：研究组中胰腺癌患者胰腺组织中Snail、Slug、E-cadherin、vimentin的表达阳性率为70.13%、68.83%、36.36%、72.73%。对照组13例正常胰腺组织中Snail、Slug均不表达,E-cadherin、vimentin的表达阳性率分别为92.31%、7.69%。胰腺癌组织中Snail表达与E-cadherin表达呈负相关（r=-0.225,P=0.025）,与vimentin表达呈正相关（r=0.493,P<0.01）;Slug表达与vimentin表达呈正相关（r=0.358,P=0.001）。Slug的表达与肿瘤分化程度及肿瘤TNM分期有关、E-cadherin的表达与淋巴结的转移与肿瘤分化程度有关、vimentin的表达与淋巴结转移、肿瘤分化程度及肿瘤TNM分期有关（均P<0.01）。 结论：Snail的高表达可能通过调控EMT过程在胰腺癌的发展过程中发挥作用,是胰腺癌浸润和转移的重要生物学指标。     

结直肠癌组织中Ezrin和E-cadherin蛋白的表达特点及意义

目的:探讨结直肠癌组织中Ezrin和钙黏素E(E-cadherin)蛋白的表达及其与临床病理因素的关系.方法:应用免疫组织化学光/微波(LW/MW)-EliVisionTM法,检测100例结直肠癌组织中Ezrin和E-cadherin的表达情况,并分析其与结直肠癌浸润转移等的关系.结果:Ezrin和蛋白在结直肠癌组织中的阳性表达明显高于正常黏膜,而E-cadherin蛋白在正常黏膜中的阳性表达高于结直肠癌组织(P＜0.05).Ezrin的高表达与结直肠癌浸润深度、淋巴结是否转移有关(P＜0.05);而与TNM分期、分化程度无关(P＞0.05).E-cadherin的表达与结直肠癌分化程度、TNM分期、浸润深度及淋巴结是否转移有关(P＜0.05).二者在结直肠癌组织中的表达呈显著负相关(r=-0.673,P＜0.01).结论:Ezrin和E-cadherin蛋白在结直肠癌的发生、发展中起着重要作用,联合检测可为结直肠癌浸润转移和预后的判断提供理论依据.     

早期胃癌淋巴结转移的多因素分析

目的探讨早期胃癌淋巴结转移的相关因素,为早期胃癌患者治疗方案的选择提供参考。方法回顾性分析2010年1月~2016年12月186例早期胃癌在我院行胃癌根治术的临床病理资料,包括性别、年龄、肿瘤大小、肿瘤部位、有无溃疡、大体分型、组织学分型、浸润深度、肿瘤数量等。采用二元logistic回归模型分析早期胃癌淋巴结转移与临床病理特征的关系,采用logistic回归模型进行多因素分析,联合上述独立影响因素分层分析早期胃癌淋巴结转移情况。结果 186例早期胃癌的淋巴结转移率为11.8%(22/186)。单因素分析显示浸润深度(P=0.020)、组织学分型(P=0.013)、有无溃疡(P=0.013)与早期胃癌淋巴结转移显著相关。多因素logistic回归分析表明浸润至黏膜下层(OR=3.370,95%CI:1.191~9.537,P=0.022)、未分化型(OR=3.325,95%CI:1.187~9.313,P=0.022)以及合并溃疡(OR=5.202,95%CI:1.144~23.662,P=0.033)是早期胃癌发生淋巴结转移的独立影响因素,其中溃疡是作用最强的影响因素。联合上3个独立影响因素分层分析显示,分化型且不合并溃疡的早期胃癌,无论浸润深度和肿瘤大小,均未见淋巴结转移(0/41),未分化型且不合并溃疡者中仅2例出现淋巴结转移,其余各组合并溃疡的早期胃癌均有淋巴结转移。结论早期胃癌浸润至黏膜下层、未分化型以及合并溃疡均易发生淋巴结转移,其中合并溃疡时发生淋巴结转移的风险最大;分化型且不合并溃疡的早期胃癌淋巴结转移风险较低,可考虑行内镜下治疗,但术后需要密切随访。     

M0期结直肠癌淋巴结外肿瘤种植的相关因素分析

目的研究结直肠癌淋巴结外肿瘤种植的影响因素。方法收集2012年1月至2014年1月249例行结直肠癌根治术病人的临床病理资料,其中男性139例,女性110例,中位年龄55岁(26~81岁);结肠癌102例,直肠癌147例;隆起型86例,溃疡型93例,浸润型70例。高分化80例,中分化102例,低分化和未分化67例。按美国癌症联合委员会(AJCC)和国际抗癌联盟(UICC)第7版TNM分期:I期55例、Ⅱ期65例、Ⅲ期129例。分析其对结直肠癌淋巴结外肿瘤种植的影响。应用SPSS(19.0版)统计软件进行统计学分析,采用卡方检验进行单因素分析,Logistic回归模型进行多因素相关分析,P=0.05为检验水准。结果入组的结直肠癌淋巴结外肿瘤种植率为17.8%(44/249);单因素分析结果显示肿瘤分化程度(P=0.0()1)、浸润深度(P=0.000)、阳性淋巴结数(P=0.000)、脉管浸润(P=0.014)、神经周围浸润(P=0.000)与淋巴结外肿瘤种植密切相关。多因素分析结果显示,与结直肠癌淋巴结外肿瘤种植相关因素的相关程度依次为:神经周围浸润(P=0.001,OR=5.401,95%CI:1.930-15.117)、脉管浸润(P=0.002,OR=3.581,95%CI:1.609-7.968)。结论结直肠癌的神经周围浸润和脉管浸润是淋巴结外肿瘤种植最主要影响因素。     

异黏蛋白表达在胃腺癌中的临床意义及其对侵袭转移的影响

目的 探索异黏蛋白在胃癌组织中的表达、调控机制及临床意义.方法 免疫组化染色检测68例胃癌组织标本异黏蛋白和E-cadherin表达,并利用x2检验等分析其对各临床病理特征和预后的影响.Transwell实验和划痕实验检测胃癌细胞侵袭迁移能力.利用小干扰RNA(siRNA)技术,特异性干扰异黏蛋白蛋白表达,观察异黏蛋白对MKN45细胞侵袭迁移的影响并探讨其调控机制.结果 胃癌组织中异黏蛋白阳性表达与肿瘤浸润深度(P =0.029)、淋巴结转移(P=0.001)、TNM分期(P=0.014)及抑制E-cadherin表达有关(P=0.001).同时,异黏蛋白阳性患者预后比其阴性患者预后更差.当下调MKN45细胞异黏蛋白表达时,则其E-cadherin表达增高,N-cadherin、Slug及Snail表达下降,且细胞的侵袭能力(P=0.027)和迁移能力(P=0.008)下降.结论 异黏蛋白通过转录因子Slug、Snail而非Twist诱导上皮间质转化过程促进胃癌的转移,并降低患者术后生存率.     

JAK2-STAT3通路和E-cadherin在结直肠癌进展中的相互作用分析

目的:探讨JAK2-STAT3通路和E-cadherin在结直肠癌进展中的相互作用。方法:选取择期行手术治疗的结直肠癌患者87例,利用Westernblot检测结直肠癌及癌旁组织中STAT3、p-STAT3和E-cadherin蛋白的表达,并计算p-STAT3/STAT3值。结果:结直肠癌组织中STAT3、p-STAT3蛋白相对表达量和p-STAT3/STAT3值均高于癌旁组织,而E-cadherin蛋白相对表达量则低于癌旁组织,差异具有统计学意义(P0.05);结直肠癌患者STAT3、p-STAT3和E-cadherin蛋白表达均与肿瘤大小、分化程度、淋巴结转移、浸润深度和TNM分期有关(P0.05);Pearson相关分析显示,结直肠癌组织中STAT3表达与p-STAT3呈正相关(r=0.736,P0.05),而与E-cadherin表达呈负相关(r=-0.497,P0.05),p-STAT3表达与E-cadherin表达呈负相关(r=-0.642,P0.05)。结论:STAT3和p-STAT3蛋白在结直肠癌组织中表达上调,可能通过激活JAK2-STAT3通路抑制E-cadherin蛋白表达而实现对肿瘤细胞浸润、转移的调控作用。     

转录因子Snail及黏附分子E-cadherin在直肠癌中的表达及意义

目的 探讨转录因子Snail及黏附分子E-cadherin在直肠癌中的表达及意义.方法 采用免疫组化SABC法检测101例直肠癌组织中Snail、E-cadherin的表达,分析二者在不同临床病理分期与分化程度的直肠癌中的表达及其与预后的关系.结果 免疫组化检测结果显示直肠癌组织中Snail的阳性表达率为78.2%(79/101),直肠癌组织中E-cadherin的阳性表达缺失率为62.4%(63/1 01),Snail与E-cadherin的表达呈显著负相关.Snail、E-cadherin的表达与直肠癌的Dukes分期及淋巴结转移有关(P＜0.05).结论 Snail蛋白的高表达和E-cadherin蛋白的低表达可能是直肠癌侵袭转移的重要生物学标志.     

胃癌神经侵犯的相关临床病理因素：单中心509例分析

目的:分析胃癌患者神经侵犯(PNI)的相关临床病理因素。方法:收集江苏大学附属医院2014年6月—2017年6月509例胃癌患者的临床和病理资料,分析PNI与患者临床病理因素的关系。结果:509例胃癌患者中,神经侵犯阳性患者250例,阴性患者259例。单因素分析显示,胃癌PNI与肿瘤浸润深度、组织分化程度、淋巴结转移和TNM分期有关(均P0.001),而与患者年龄、性别无关(均P0.05);趋势χ~2检验显示胃癌PNI与肿瘤浸润深度相关性最大(r=0.623,P0.001);二分类Logistic回归分析表明肿瘤浸润深度为胃癌神经侵犯的独立危险因素(OR=6.285,95%CI=4.009~9.854,P0.001)。结论:胃癌患者PNI与肿瘤浸润深度、组织分化程度、淋巴结转移数目和TNM分期有关,其中肿瘤浸润深度可能是最重要的因素。     

EphA2和E-cadherin在胃癌中的表达及其意义

目的:探讨EphA2与E-cadherin在胃癌组织中的表达及其意义。方法:采用免疫组织化学SP法检测EphA2与E-cadherin蛋白在胃癌组织、癌旁组织和远癌胃组织中的表达情况，分析它们与胃癌临床病理特征之间的关系及两种蛋白间的相关性。结果:EphA2在胃癌组织中呈高表达(P＜0.01)，其高表达与胃癌的浸润深度、肿瘤TNM分期以及淋巴结转移有关(P＜0.05);E-cadherin在胃癌组织中呈低表达(P＜0.01)，其低表达与胃癌的浸润深度、肿瘤分化程度、肿瘤TNM分期以及淋巴结转移有关(P＜0.05);胃癌组织中EphA2和E-cadherin蛋白表达呈负相关(r=-0.602，P＜0.001)。结论:EphA2的高表达和E-cadherin的低表达与胃癌的发展和转移密切相关，EphA2可望作为胃癌治疗的新靶点。     

自噬相关蛋白Beclin 1在胃癌组织中表达意义的Meta分析

目的:系统评价胃癌组织中自噬相关蛋白Beclin 1(BECN1)的表达及其与胃癌患者临床病理特征之间的相关性。方法:检索国内外相关数据库,收集2015年2月1日前发表的关于胃癌组织中BECN1的表达及其临床意义的研究,提取相关数据,采用Rev Man 5.3及Stata12.0软件进行Meta分析。结果:最终纳入了9个研究,其中包含胃癌患者1 620例。Meta分析结果显示,胃癌组织中BECN1的表达阳性率明显低于非胃癌组织(OR=0.11,95%CI=0.02~0.62,P=0.01);高分化胃癌组织的BECN1表达阳性率明显高于中低分化胃癌组织(OR=14.30,95%CI=5.94~34.4,P=0.000);无远处转移患者的胃癌组织中BECN1表达阳性率明显高于有远处转移者(OR=0.39,95%CI=0.22~0.70,P=0.001);BECN1表达与胃癌患者性别、年龄、肿瘤浸润深度、淋巴结转移及TNM分期等无关(均P0.05)。结论:BECN1在胃癌的发生和胃癌细胞分化中可能起重要作用,且BECN1可能参与了胃癌细胞转移能力的调控。     

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.     

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.     

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.