丝裂素激活蛋白激酶活化与肾小管上皮细胞生物学行为的关系

目的探讨丝裂素激活蛋白激酶(MAPK)信号通路对血小板源生长因子(PDGF)诱导肾小管上皮细胞表型转化的作用及其对细胞移行能力的影响.方法以PDGF(20 ng/ml)刺激培养的人近端肾小管上皮HK-2细胞,分别观察细胞形态、增殖和移行能力的变化.采用蛋白免疫印记法检测MAPK各亚类活性及α-平滑肌肌动蛋白(SMA)的表达,同时观察分别采用细胞外信号调节激酶(ERK)、c-Jun氨基末端激酶(JNK)和p38信号通路特异阻断剂PD98059、SP600125和SB203580后上述指标的变化.结果 PDGF刺激6～12 h使α-SMA表达上调近2倍,但刺激24～48 h反而使α-SMA表达低于基础水平.PDGF刺激24 h后HK-2细胞从立方形转变为梭形,细胞虽尚无增殖反应但移行能力增强至3倍(P＜0.01).PDGF诱导的ERK、JNK和p38活性均在2 min时迅速增高,分别在2～5 min达高峰,分别为基础水平的5.7倍、2.6倍和1.6倍(P＜0.05),ERK和JNK活性增高可持续至120 min,而p38活性则于60 min以后恢复至基础水平.在PDGF刺激24 h的情况下,PD98059和SP600125不影响基础状态及PDGF对α-SMA表达的作用,但SP600125可抑制PDGF上调的细胞移行能力(P＜0.01);而SB203580既可抑制α-SMA的基础表达(P＜0.01)及PDGF下调的α-SMA表达(P＜0.001),同时还可显著抑制PDGF诱导的细胞移行能力(P＜0.05).结论 PDGF可刺激MAPK的不同亚类信号通路磷酸化,并可诱导肾小管上皮细胞形态改变及其移行能力增强.在PDGF诱导的表型转化和移行功能改变中,ERK信号通路无介导作用,JNK通路主要与细胞移行能力变化相关,而p38可能是调控α-SMA表达和细胞移行改变的主要信号通路.     

肝星状细胞中蛋白激酶C活性改变对其表达血小板源生长因子及增殖的影响

目的观察蛋白激酶C（PKC）活性改变对肝星状细胞（HSC）表达血小板源生长因子（PDGF）的影响及对HSC增殖和激活的作用。方法将肝星状细胞系rHSC-99随机分为3组：对照组（A组）；PKC激动剂PMA0．5μmol／L组（B组）；PKC抑制剂Calphostin C100nmol／L组（C组）。加药后0、3、6、12、24h分别检测各组细胞PKC活性的变化；作用24h后，采用Westernblot方法检测各组细胞PDGF和胞外信号调节激酶（ERK）的表达；采用免疫荧光化学方法检测各组细胞α-平滑肌肌动蛋白（α—SMA）的表达；采用MTT法检测细胞的增殖情况。结果PMA作用后PKC的活性显著增强，而Calphostin C则抑制PKC的活性。PKC活性增强后，与对照组比较HSC的PDGF表达升高了1．4倍（P〈0．01），ERK表达升高了1．2倍（P〈0．05）；n—SMA的表达升高了1．3倍（P〈0．01），并促进HSC的增殖；PKC活性抑制后则能抑制以上的作用。结论PKC活性的改变能调控HSC中PDGF的表达，在HSC的增殖和激活中发挥调节作用。     

丝裂原蛋白激酶信号转导通路在机械通气相关性肺损伤中的作用

目的观察机械通气介导肺损伤（VILI）过程中丝裂原蛋白激酶（MAPK）的活性变化以及对细胞因子的影响，从中探讨VILI发生机制和MAPK的作用。方法72只SD大鼠随机分为未处理的对照组（不行机械通气）、正常通气组、过度通气组和采用MAPK抑制剂SP600125（JNK）、SB203580（p38）、PD98059（ERK）分别预处理上述3组。机械通气4h后取大鼠肺组织采用Western blot方法测定各组的总JNK、ERK、p-38蛋白激酶的表达及其磷酸化水平变化。同时以酶联免疫吸附试验（EUSA）方法测定大鼠肺组织、支气管肺泡灌洗液（BALF）和血浆中的肿瘤坏死因子-α（TNF-α）、巨噬细胞炎性蛋白-2（MIP-2）浓度。结果正常和过度机械通气4h后均能激活JNK、ERK、p38激酶，但以过度通气组为著（P〈0．01）。过度通气组大鼠肺组织、BALF、血浆中的TNF-α、MIP-2含量显著高于其他组（P〈0．01）。JNK、ERK、p38抑制剂显著降低肺组织、BALF中的TNF-α、MIP-2含量（P〈0．05或0．01），且JNK和ERK抑制剂作用强于p38抑制剂。结论过度机械通气激活了肺细胞中的JNK、ERK、p38激酶，且JNK、ERK、p38参与了VILI细胞因子的产生，即MAPK信号转导通路的激活可能是VILI发生机制之一。     

转化生长因子β1对肾小管上皮细胞中结缔组织生长因子基因启动子活性的影响

目的探讨转化生长因子[β1（TCF-β1）对人近端肾小管上皮细胞系HK-2中结缔组织生长因子（CTGF）基因启动子活性的调控作用，以及丝裂原激活蛋白激酶（MAPK）途径对该生长因子作用的影响。方法构建含有人类CTGF基因启动子的报告基因pCTGF-luc，将其瞬时转染HK-2细胞。通过检测荧光素酶的活性观察TGF-β1和MAPK途径抑制剂对CTGF基因启动子活性的影响。结果TGF-β1以剂量和时间依赖方式上调HK-2中CTGF基因启动子的活性。最佳刺激浓度是5ng／ml，最佳刺激时间为12h，荧光素酶相对活性分别为对照组的1．82倍和2．10倍（P〈0．05）。应用PD98059、SB203580和SP600125分别特异性抑制MAPK途径的胞外信号调节蛋白激酶（ERK）、蛋白激酶p38（p38MAPK）和c-Jun-氨基末端激酶（JNK）通路，对TGF-β1上调CTGF启动子活性的作用有不同影响。PD98059显著增加HK-2中pCTGF-luc的基础活性．并在一定浓度范围内（0．5～10μmol／L）促进TGF-β1的上调作用。SB203580对pCTGF-luc基础活性无影响，但以剂量依赖方式显著抑制TGF-β1的激活效应。而SP600125对基础状态和TGF-β1刺激下CTGF基因启动子活性无影响。结论TGF-β1以剂量和时间依赖方式上调HK-2中CTGF基因启动子活性，在转录水平调节CTGF表达。MAPK途径的ERK和p38MAPK通路可影响TGF-β1的这一调控作用。     

JNK对转化生长因子β1所致大鼠腹膜间皮细胞转分化的调控作用

目的 探讨c-Jun 氨基末端激酶(JNK)在转化生长因子β1(TGF-β1)诱导大鼠腹膜间皮细胞（RPMC）转分化中的调控作用。 方法 采用腹腔注射胰蛋白酶法分离培养RPMC，取第2代腹腔间皮细胞用于实验研究。观察TGF-β1对α平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(ColⅠ)、E钙黏蛋白(E-cadherin)以及磷酸化(p)JNK表达的影响；应用JNK特异性抑制剂SP600125预处理细胞后，观察其对TGF-β1所致上述作用的影响。RT-PCR法检测α-SMA、ColⅠ及E-cadherin mRNA表达；Western印迹法检测α-SMA、ColⅠ、E-cadherin及p-JNK蛋白表达；间接免疫荧光检测α-SMA在细胞内的表达和分布。 结果 TGF-β1刺激RPMC能导致α-SMA、ColⅠ蛋白表达上调，E-cadherin蛋白表达下调，呈时间依赖性。TGF-β1刺激RPMC 5 min出现p-JNK表达上调，10 min达高峰(P < 0.01)。SP600125能够抑制JNK的磷酸化(P < 0.05)，也能抑制TGF-β1诱导的α-SMA、ColⅠmRNA和蛋白的高表达以及E-cadherin表达的下调 (均P < 0.05)。间接免疫荧光结果显示，TGF-β1刺激RPMC 48 h，胞内α-SMA表达明显增多，SP600125能有效抑制其高表达。 结论 JNK在TGF-β1诱导大鼠腹膜间皮细胞转分化中具有重要的调控作用，JNK特异性抑制剂的应用可能为临床防治腹膜纤维化提供新的途径。     

MAPK信号传导通路在髓核细胞研究进展

丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)是将细胞外刺激信号转换成广泛的细胞内反应的一类丝氨酸/苏氨酸蛋白激酶,在许多生理过程中发挥着重要的细胞信号传导的作用[1].在真核细胞生物中,MAPK信号通路在基因表达、细胞增殖、分化、凋亡、新陈代谢等生理病理过程中发挥着重要的作用.在哺乳类动物中,MAPK家族基因有10来个,目前研究发现常见的MAPK信号通路有:细胞外信号调节激酶(ERK1/2),c-Jun氨基末端激酶(JNK1/2/3),p38激酶(α,β,γ,δ)以及大丝裂原活化蛋白激酶(ERK5/BMK1) [2-4].每一个常见的信号通路都存在三级激酶级联,细胞受外部信号刺激后通过MAPKKK转化为细胞内的信号并进一步磷酸化激活MAPKK,最后MAPKK通过双重磷酸化进一步激活MAPK,进而引起一系列细胞内信号的改变,在细胞增殖及功能上发挥着重要的作用.研究腰椎间盘退变过程中髓核细胞MAPK信号通路的信号变化将有助于人类对退行性腰椎间盘病进一步认识,并可能从中找到治疗退行性腰椎间盘病的方法.本文将综述MAPK常见信号通路在髓核细胞的研究进展.     

晚期糖基化产物受体信号传导在羧甲赖氨酸诱导足细胞表达单核细胞趋化因子中的作用

目的 了解足细胞上晚期糖基化产物受体（RAGE）激活后的细胞内信号的传导途径.方法 激光共聚焦显微镜观察细胞内反应性氧自由基（ROS）的产生.Western印迹方法检测足细胞内丝裂原激活的蛋白激酶（MAPK）家族磷酸化,RT-PCR方法检测单核细胞趋化因子-1（MCP-1）的mRNA表达.结果 足细胞细胞核内存在基础性的ROS,AGE和羧甲赖氨酸（carboxymethyllysine,CML）分别诱导细胞浆内ROS增加2.2和2.6倍.N-乙酰-L-半胱氨酸（NAC）抑制基础性和诱导性ROS形成,RAGE中和抗体则完全抑制诱导性的ROS产生.NAC也可直接抑制CML以及外源性H2O2诱导的MCP-1的表达.使用CML刺激足细胞10 min后,磷酸化细胞外信号调节激酶（ERK）增加3.8倍.而CML刺激足细胞120 min仍没有发现磷酸化的p38MAPK和应激活化蛋白激酶（SAPK）/氨基末端激酶（JNK）表达或上调.使用NAC,7氨4三氟甲基香豆素（AFC）可以完全防止ERK磷酸化并抑制MCP-1的mRNA表达.PD98059阻断了ERK磷酸化却并不能完全抑制MCP-1的mRNA的表达.结论 足细胞上RAGE激活后,通过ROS-p21Ras-ERK信号途径诱导足细胞表达MCP-1.     

他莫昔芬通过丝裂原活化蛋白激酶抑制前列腺癌细胞系PC3细胞增殖

他莫昔芬是选择性雌激素受体（ER）调节剂（SERM）。丝裂原活化蛋白激酶（MAPK）主要包括细胞外信号调节蛋白激酶（ERK1／2）、c-JunN端应力激活蛋白激酶（JNK）和p38丝裂原活化蛋白激酶（p38）。他莫昔芬（TAM）通过ER可以激活MAPK。本实验旨在研究MAPK信号转导通路在他莫昔芬抑制雄激素非依赖性前列腺癌细胞株PC3生长中的作用。[第一段]     

MAPK信号通路与勃起功能障碍关系的研究进展

MAPK信号通路在细胞的分化、增殖及凋亡等过程中起着十分关键的作用。MAPK家族的信号通路主要包括细胞外信号调节蛋白激酶(ERK),应激活化蛋白激酶(JNK)、p38丝裂原活化蛋白激酶(p38MAPK)等。从目前的研究来看,ERK、JNK、p38MAPK 3条信号通路与ED的发生发展紧密联系。本文根据相关文献对MAPK信号通路与勃起功能障碍作一综述。     

活化蛋白激酶在骨肉瘤中的表达及其意义

[目的]探讨细胞分裂素活化蛋白激酶（MAPK）中细胞外信号调节蛋白激酶（ERK）、c-jun氨基末端激酶（JNK）、P38三条通路在骨肉瘤发生中的作用。[方法]用免疫组织化学技术EnVision^TM法检测48例骨肉瘤标本及25例成骨性良性肿瘤标本中ERK、JNK、P38蛋白的表达，并比较他们的差异。[结果]ERK、JNK、P38三种蛋白在骨肉瘤组的阳性率分别为83．3％（40／48），72．9％（35／48）和85．4％（41／48），在成骨性良性肿瘤组中的阳性率分别为16．0％（4／25），12．0％（3／25）和20．0％（5／25），骨肉瘤组织中ERK、JNK、P38蛋白阳性率及阳性强度均明显高于成骨性良性肿瘤（P〈0．01）。[结论]MAPK中ERK、JNK、P38三条通路在骨肉瘤发生中均发挥了重要作用，用免疫组织化学方法检测MAPK，可为临床骨肉瘤与良性骨肿瘤的诊断与鉴别诊断提供参考指标。     

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.     

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.     

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.     

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.     

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.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.