雄激素对前列腺癌细胞PAR基因表达的影响及其机制

目的观察在前列腺癌特异性高表达的癌基因前列腺雄激素调节基因（PAR）对雄激素的反应及其机制，探讨通过抑制PAR基因治疗雄激素非依赖性前列腺癌的可能性。方法用细胞计数检测双氢睾酮对LNCaP、PC3细胞增殖的刺激效应，以逆转录-聚合酶链反应（RT-PCR）分别检测双氢睾酮对LNCaP、PC3细胞PAR基因mRNA表达水平的影响及双氢睾酮和其拮抗剂联合作用对LNCaP细胞PAR基因mRNA表达水平的影响。结果低浓度（0．001～1nmol／L）双氢睾酮刺激可促进LNCaP细胞增殖，且刺激效应随双氢睾酮浓度升高而增强，在0．1nmol／L浓度时达最大，细胞计数为（27、54±0．71）×10。爪／孔，为对照组（16．13±1．03）×10。爪／孔的（170．74±0．78）％；同时使PAR基因mRNA表达水平上调在0．1nmol／L浓度时最高，为对照组的（272．42±8．24）％，P〈0．05）；高浓度（10、100nmol／L）双氢睾酮则抑制其增殖和PAR基因表达，在10nmol／L和100nmol／L浓度，细胞计数分别为（12．02±0．41）×10。／孔、（11．13±1．92）×10^4／孔（P〈0．05）；PAR基因mRNA表达水平分别为对照组的（76．64±2．47）％和（52．97±1．07）％，（P〈0．05）。这一调节效应可以为氟他胺所阻断。双氢睾酮对PC3细胞生长及PAR基因mRNA表达无明显影响（P〉0．05）。结论PAR可能是雄激素．雄激素受体通路下游的前列腺癌特异性癌基因，有望成为雄激素非依赖性前列腺癌基因和药物治疗的潜在靶点。     

MAPK途径磷酸化激活人前列腺癌雄激素受体的研究

目的研究粒细胞-巨噬细胞集落刺激因子（GM-CSF）激活人激素非依赖性前列腺癌PC-3M细胞雄激素受体及其可能的信号转导途径。方法将人雄激素受体和雄激素受体激活报告基因氯霉素乙酰转移酶（CAT）转染至人雄激素非依赖性前列腺癌细胞株PC-3M,不同浓度的GM- CSF以及特异性Erk1／2磷酸化阻断剂PD98059作用后检测雄激素受体报告基因CAT表达量的变化和促分裂素原活化蛋白激酶（MAPK）途径：Erk1／2分子磷酸化的改变。结果20～100 nmol／L的GM-CSF均能激活PC-3M细胞的外源性雄激素受体,CAT的相应表达量为（0．58±0．16）～（3．80±0．89）ng／mg,CAT表达量与培养基中的GM-CSF浓度成正相关;同时检测到PC-3M细胞中Erk1／2分子磷酸化程度与培养基中的GM-CSF浓度相关,在终浓度50 mmol／L的PD98059阻断Erk1／2分子磷酸化后CAT表达量显著下降。结论GM-CSF能独立激活前列腺癌PC-3M细胞中的雄激素受体,Erk1／2分子磷酸化可能是GM-CSF旁路激活人前列腺癌细胞雄激素受体的机制。     

前列腺癌患者去势术后的睾酮水平

目的 探讨进展期前列腺癌患者去势术后平均睾酮水平，以指导内分泌治疗。方法 进展期前列腺癌患者40例，去势术后，未用任何抗雄激素药物，分别于术前、术后1周及1、3、6、9、12个月，观察血清总睾酮和PSA变化。结果 去势术后6个月，40例患者血清睾酮平均水平〈1．9nmol／L（95％可信区间1．2～1．9nmol／L）；13例患者睾酮〉1．9nmol／L，平均Gleason评分为6．8分。术后6个月，36例患者PSA〈1ng／ml，平均Gleason评分为6．3分；4例患者PSA〉1ng／ml，平均Glcason评分为8．0分。结论 前列腺癌患者去势术后，平均血清睾酮水平〈1．9nmol／L，部分患者需继续抗雄激素药物治疗。术后PSA逐渐下降，6个月降至最低值。     

正常人血清前列腺特异性抗原水平的研究

目的：评价年龄与血清前列腺特异性抗原（PSA）水平的关系。方法：采用免疫放射分析（IRMA）测定226例正常男性各年龄组血清PSA水平。结果：30～39岁组血清PSA为（0．88±O．47）ng／ml，40～49岁组为（0．87±0．34）ng／ml，50～59岁组为（0．99±0．57）ng／ml，60～69岁组为（1．12±0．78）ng／ml，＞70岁组为（1．12±0．83）ng／ml，各组间血清PSA浓度无显著性差异（P＞0．05）。结论：当前列腺体积在正常范围内时，血清PSA水平与年龄无直接关系。     

非那雄胺在晚期前列腺癌治疗中的作用

目的：探讨非那雄胺加间歇性雄激素阻断在晚期前列腺癌治疗中的作用。方法：将33例T3。期或T4期前列腺癌患者分为两组,A组18例采用比卡鲁胺加戈舍瑞林,间歇性雄激素阻断治疗;B组15例采用非那雄胺加比卡鲁胺加戈舍瑞林治疗。间歇期内B组继续服用非那雄胺。结果：治疗后9个月,A组13例完全缓解．3例部分缓解,2例无变化,有效率为88．9％。前列腺特异性抗原（PSA）为0．3～37．3ng／ml,平均（7．6±6．5）ng／ml。B组12例完全缓解,2例部分缓解,1例无变化,有效率为93．3％。PSA为0．1～10．5ng／ml,平均（4．2±2．8）ng／ml。B组PSA值低于A组,差异有统计学意义（P〈0．05）。随访61．7（31～82）个月,B组停药间期（25．1±10．1）个月长于A组（15．7±8．6）个月（P〈0．05）。A组5年生存率为55．6％（10／18）,B组为66．7％（10／15）,差异无统计学意义（P〉0．05）。治疗后5年,A组仍有6例有效（33．3％）,B组8例有效（53．3％）,差异无统计学意义（P〉0．05）。结论：非那雄胺加上间歇性雄激素阻断治疗,能使晚期前列腺癌PSA进一步降低,停药间期延长。     

前列腺癌根治术后精囊侵犯患者的临床资料分析

目的：评估21例前列腺癌根治术后精囊侵犯患者的预后及其治疗影响因素。方法：回顾性分析2001～2006年行耻骨后前列腺癌根治性切除术的前列腺癌患者临床资料,术后定期门诊随访,其中21例术后病理检查提示单侧或双侧精囊侵犯,中位年龄70（48～79）岁;术前PsA〈10ng／ml7例,10～20ng／ml 9例,〉20ng／ml5例;Gleason分级2～6分3例,7分8例,≥8～9分10例。以根治术后连续2次PSA水平超过0．2ng／ml定义为生化复发;以根治术后随访时发生生化复发或截止到随访时还没有发生生化复发的时间定义为无生化复发生存时间。术前PSA〈10ng／ml且Gleason分级为2～6分的患者进行等待观察治疗,Gleason分级≥7分或PSA≥10ng／ml的患者接受单纯抗雄激素治疗、最大限度雄激素阻断治疗或最大限度雄激素阻断治疗＋外放疗。结果：21例患者随访34～106个月,3例进行等待观察治疗,7例进行单纯抗雄治疗,6例进行最大限度雄激素阻断治疗,5例进行最大限度雄激素阻断＋外放疗;其中1例发生骨转移,发展为激素难治性前列腺癌。21例患者无死亡。5年无生化复发存活时间在等待观察组、单纯抗雄激素治疗组、最大限度雄激素阻断治疗组及外放疗＋最大限度雄激素阻断治疗组间的差异无统计学意义。结论：前列腺癌根治术后精囊侵犯者的预后尚可,Gleason分级≤6分、PSA水平低者可采取等待观察;PSA≥10ng／ml且Gleason分级≥7分者术后给予辅助治疗可提高无生化复发生存率,且单纯抗雄激素治疗比最大限度雄激素阻断治疗和外放疗＋最大限度雄激素阻断治疗经济、并发症少,生活质量高。     

尿激酶及其受体对膀胱癌细胞系侵袭转移影响的体外研究

目的：探讨尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR）与膀胱癌侵袭转移的关系。方法：对BIU-87、T24及EJ细胞系进行体外培养，夹心抗体ELISA法测定细胞培养上清及细胞溶解产物uPA含量，对培养细胞团块行uPAR免疫组化测定，并进行体外人工基底膜侵袭检测。结果：BIU-87、T24和EJ细胞培养上清uPA检测结果分别为（11．77±3．65）ng／ml、（8．70±2．45）ng／ml、（105．9±8．60）ng／ml，EJ细胞培养上清uPA明显高于BIU87和T24细胞系（P〈0．001）。细胞溶解产物uPA结果分别为（1．15±0．40）ng／ml、（0．78±0．34）ng／ml、（1．92±0．56）ng／ml，EJ细胞溶解产物uPA含量明显高于BIU-87、T24细胞溶解产物（P〈0．02，P〈0．01）。EJ细胞uPAR蛋白主要弥散于细胞质，着色强度与数量明显多于T24细胞（P〈0．01），而BIU-87细胞基本无着色。EJ细胞具有浸润Matrigel的能力，BIU-87、T24无浸润Matrigel能力。结论：肿瘤细胞有uPA的分泌或来源并同时表达uPAR在体外即具备浸润能力，uPA系统在膀胱肿瘤的浸润转移过程中起重要作用。     

卡介苗膀胱灌注后尿白细胞介素2及肿瘤坏死因子含量测定及意义

目的：寻找能早期评估表浅膀胱癌术后行卡介苗（BCG）免疫治疗效果的精确指标。方法：分别采用CTLL－3H－TdR掺入法及夹心法酶联免疫吸附试验，测定32例表浅膀胱癌术后行BCG膀胱灌注者尿液中白细胞介素2（IL-2）及肿瘤坏死因子（TNF）含量。结果：全部病例均获随访26～67个月，平均43．5个月。32例中有6例复发（18．7％），复发患者灌注后尿液中IL－2及TNF含量分别为（14．34±6．83）u／ml及（78．63±37．45）ng／L，未复发患者IL-21、TNF含量分别为（21．41±9．23）u／ml及（106．76±49．13）ng／L，复发与未复发患者间IL－2、TNF水平比较均有显著性差异（分别P＜0．01和＜0．05）。结论：测定尿液中IL-2及TNF含量对判断表浅膀胱癌术后BCG灌注治疗的预后有重要的参考价值。     

间歇性与持续性雄激素阻断治疗晚期前列腺癌疗效比较

目的 比较间歇性与持续性雄激素阻断治疗晚期前列腺癌的疗效和副反应。方法 晚期前列腺癌患者69例，分2组。A组34例行间歇性联合雄激素阻断治疗，B组35例行手术去势加抗雄激素药物即持续性雄激素阻断治疗。比较2组患者的疾病进展时间和副反应发生率。结果 A组中位随访31．5（10～60）个月，B组32．6（12～63）个月。A组患者共行60个周期治疗，平均治疗周期13．7个月，其中治疗期6．4个月、间歇期7．3个月。A、B组中位疾病进展时间分别为31、28个月，差异无统计学意义（P=0．446）；骨转移患者中A组中位疾病进展时间24个月，B组为18个月，2组比较差异有统计学意义（P=0．04）。2组副反应发生率分别为：潮热症状A组20．6％（7／34），B组62．9％（22／35）（P〈0．01）；骨质疏松A组11．8％（4／34），B组31．4％（11／35）（P〈0．05）；乳房肿痛A组14．7％（5／34），B组37．1％（13／35）（P〈0．05）。结论 对晚期前列腺癌患者行雄激素阻断治疗应首选间歇性联合雄激素阻断治疗。     

存活素基因表达与前列腺癌激素依赖性的实验研究

目的探讨存活素(survivin)基因表达与前列腺癌激素依赖性间的关系。方法应用雄激素依赖性前列腺癌细胞系LNCaP和非依赖性细胞系PC3构建2种。BALB／C鼠肿瘤模型,每组16只。采用逆转录-聚合酶链反应(RT-PCR)和Western blot方法检测动物去势术前后2种癌结节中存活素基因和蛋白的水平。结果2种癌结节中均检测到存活素mRNA,而在非癌组织均未检测到。LNCaP组去势手术前、后存活素mRNA表达值分别为0．95±0．12和0．80±0．10;PC3组分别为0．93±0．11和0．85±0．10,2组间及组内比较差异均无统计学意义(P>0．05)。LNCaP组术前蛋白含量相对值(1．25±0．15)与PC3组(1．15±0．10)比较差异无统计学意义(P=0．220)。去势术后LNCaP组蛋白水平(0．48±0．08)显著下降(P=0．001),而PC3组(0．90±0．10)与术前比较差异无统计学意义(P>0．05)。结论存活素基因转录后水平的调控差异可能是前列腺癌对激素依赖性差异的机理之一。     

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.