烧伤后肾组织内皮素-1 及其受体基因的表达

目的探讨烧伤后肾组织内皮素－１（ＥＴ－１）升高的效应部位以及效应的ＥＴＲ亚型。方法采用斑点杂交和原位杂交技术对大鼠３０％体表面积Ⅲ度烧伤模型的ＥＴ－１及其受体亚型（ＥＴＡ、ＥＴＢ）的基因表达进行了研究。结果烧伤后１小时，ＥＴ－１、ＥＴＡ、ＥＴＢ、ｍＲＮＡ均明显升高；烧伤后２４小时仍维持较高水平。ＥＴ－１和ＥＴＡｍＲＮＡ杂交信号于烧伤后３小时达高峰。ＥＴ－１ｍＲＮＡ主要分布肾皮质小血管内皮细胞、髓质肾小管和集合管，ＥＴＡ受体ｍＲＮＡ则分布于上述小血管的平滑肌细胞。ＥＴＢ受体ｍＲＮＡ于烧伤后６小时达高峰，主要分布髓质肾小管、集合管。结论烧伤后肾脏内皮素受体亚型上调在皮质以ＥＴＡ为主，在髓质以ＥＴＢ为主，它们分别与增强表达的ＥＴ－１结合可能导致肾皮质缺血和水钠代谢异常，是烧伤后肾功能障碍的重要因素。     

缺血再灌流肾组织内皮素—1及其受体基因表达的实验研究

为了探究内皮素１（ＥＴ１）对肾功能的影响和作用方式，采用斑点杂交和原位杂交方法对大鼠缺血６０分钟再灌注肾组织ＥＴ１及其受体亚型（ＥＴＡ、ＥＴＢ）的基因表达进行了研究。结果发现：再灌流１小时，ＥＴ１、ＥＴＡ、ＥＴＢｍＲＮＡ均明显升高；再灌流２４小时仍维持较高水平。ＥＴ１和ＥＴＡｍＲＮＡ杂交信号再灌流３小时达高峰。ＥＴ１ｍＲＮＡ主要分布肾皮质小血管内皮细胞、髓质肾小管和集合管，ＥＴＡ受体ｍＲＮＡ则分布于上述小血管的平滑肌细胞。ＥＴＢ受体ｍＲＮＡ于再灌流６小时达高峰，主要分布髓质肾小管、集合管。说明缺血再灌流肾内皮素受体亚型上调在皮质以ＥＴＡ为主，在髓质以ＥＴＢ为主，分别与增强表达的ＥＴ１结合导致肾皮质缺血和水钠代谢异常。     

内皮素对阻塞性黄疸肾功能影响的实验研究

目的：研究内皮素与阻塞性黄疸肾功能障碍的关系,方法：大鼠胆总管结扎后分为5天,10天、15天3组,同时建立相应的对照组,观察血和肾组织内皮素与肝肾功能的变化,并用原位杂交观察肾组织ET－1mRNA的表达。结果：随着胆管梗阻时间的延长,血和肾组织内皮素持续升高,与内生肌酐清除率,肾皮质血流量呈明显负相关,肾小球,肾小管,集合管,肾内小血管ET－1 mRNA的表达持续增加,排钠分数梗阻5天时升,15 时低于对照组,结论：内皮素是引起阻塞性黄疸肾功能障碍的原因之一,肾组织内ET水平升高是由于肾小管,集合管,肾内小血管ET－1mRNA表达升高的缘故,在阻黄早期ET可促进利尿排钠,后期则可抑制水钠排泄。     

内皮素受体拮抗剂对肝硬化、门静脉高压大鼠内皮素受体mRNA表达的影响

内皮素(ET) 1是强力缩血管物质,在门静脉压力升高和维持中起重要作用[1] ,ET 1通过与其受体结合而发挥作用。ET受体至少可分为两种亚型,即ETA受体(ETRA)和ETB受体(ETRB) ,其中ETRB根据介导的舒张和收缩作用又分为ETRB1和ETRB2 [2 ] 。本实验旨在观察CCl4诱导的肝硬化、门静脉高压大鼠门静脉压力、肝组织ET受体mRNA表达的变化以及ETA受体拮抗剂(BQ 12 3 )、ETB受体拮抗剂(BQ 788)及两者联合应用对研究结果的影响。一、材料与方法1.实验对象:雄性SD大鼠,体重3 70～40 0 g ,参照文献[3 ]方法制备肝硬化、门静脉高压模型…     

内皮素受体在雄激素非依赖性前列腺癌中的作用

目的 研究雄激素非依赖性前列腺癌株PC3中内皮素(ET)受体表达及受体阻断后PC3细胞的凋亡情况。方法 RT-PCR法测定PC3中ET受体的表达以及采用受体拮抗剂干预后其表达的变化,通过流式细胞仪和透射电镜研究干预后PC3细胞凋亡的情况。结果 PC3中ETA表达较高,而ETB表达非常弱。ETA受体拮抗剂干预后,ETA表达明显减少,随干预浓度的增加,PC3细胞凋亡的比例逐渐增加;而ETB受体拮抗剂干预后无明显改变。结论 PC3中ET-1的作用主要通过ETA受体介导,ETB受体是静止的。ETA受体阻断后,表达减少,PC3细胞出现凋亡,并呈剂量依赖关系。     

大鼠烧伤早期血浆内皮素变化及其对内皮细胞通透性的影响

为探讨烧伤早期内皮素变化及不同浓度ET-1对培养血管内皮细胞通透性的影响,动态观察了大鼠30％Ⅲ度烧伤早期血浆内皮素变化规律及其对内皮细胞通透性的直接影响。结果表明:血浆ET浓度伤后迅速升高,6小时达峰值,以后虽有所回落,但24小时内仍显著高于基础水平(P<0.01);培养血管内皮细胞单层与0,1,10,100nmol/L ET-1孵育后,其对Hank’s液或白蛋白灌注液的滤过流量、滤过系数均明显增加,而对蛋白渗透压反射系数显著减少,且存在剂量依赖性。提示烧伤后异常增高的ET除发挥其强大的缩血管作用,调节血流分布外,还直接促进了烧伤后毛细血管通透性的增加。     

大鼠烧伤早期各内脏内皮素的变化

目的探讨烧伤后内皮素变化及其在内脏损害中的作用。方法采用大鼠３０％Ⅲ度烧伤模型动态观察大鼠烧伤后血浆、心、肝、肺、肾脏内皮素的变化规律及应用非选择性内皮素受体拮抗剂ＰＤ１４５０６５对烧伤大鼠内脏损害的作用。结果正常大鼠４种脏器每克组织中内皮素含量以肺脏最高，其次为肾、肝、心脏，血浆、肝、肾、肺脏内皮素含量伤后２小时均明显升高，６小时达峰值，２４小时内仍高于伤前；心脏内皮素含量与上述变化类似，但伤后１２小时达峰值，且升高幅度较其它脏器低；肝肾内皮素的升高与伤后相应肝、肾血流量减少呈明显负相关。应用ＰＤ１４５０６５不仅可使肝、肾血流量显著回升，而且明显降低心、肝、肺、肾脏器含水量，减轻内脏损害。结论烧伤后内皮素的异常改变一定程度上参与了烧伤早期内脏损害     

大鼠烧伤早期各内脏内皮素的变化

目的探讨烧伤后内皮素变化及其在内脏损害中的作用。方法采用大鼠30％Ⅲ度烧伤模型动态观察大鼠烧伤后血浆、心、肝、肺、肾脏内皮素的变化规律及应用非选择性内皮素受体拮抗剂PD145065对烧伤大鼠内脏损害的作用。结果正常大鼠4种脏器每克组织中内皮素含量以肺脏最高,其次为肾、肝、心脏,血浆、肝、肾、肺脏内皮素含量伤后2小时均明显升高,6小时达峰值,24小时内仍高于伤前;心脏内皮素含量与上述变化类似,但伤后12小时达峰值,且升高幅度较其它脏器低;肝肾内皮素的升高与伤后相应肝、肾血流量减少呈明显负相关。应用PD145065不仅可使肝、肾血流量显著回升,而且明显降低心、肝、肺、肾脏器含水量,减轻内脏损害。结论烧伤后内皮素的异常改变一定程度上参与了烧伤早期内脏损害。     

内皮素受体亚型非选择拮抗剂(TAK-044)对移植肝的保护作用

作者报道在肝缺血模型上发现肝组织再灌注后血浆内皮素－1（ET－1）水平明显增高。而且ET－1单克隆抗体或内皮素A／B（ETA＼ETB）受体非选择性拮抗剂TAK－044能显著改善缺血一再灌注所致的肝功能损害和形态学的异常。人肝移植后，患者血浆ET－1水平显著升高，由此可见，ETA／ETB受体拮抗剂可能对移植肝起保护作用。本实验的目的就是为了观察TAK－044对猪的肝移植是否具有肝保护作用。方法：从供体猪体内取出肝脏，存放于冷的Eurocolling溶液待用，采用原位吻合术将供体肝移植于受体诸体内。在肝上静脉—腔静脉吻合完成前，分成两…     

应用分子原位杂交技术检测大鼠烧伤后脏器内皮素mRNA表达

本实验动态观察大鼠烧伤后血浆内皮素（ＥＴ）变化，同时应用分子原位杂交技术检测了大鼠烧伤后心、肺、肝、肾等主要脏器ＥＴ－１ｍＲＮＡ的表达及细胞定位。结果显示，烧伤后血浆内皮素浓度迅速升高，伤后６小时达高峰，２４小时仍维持较高水平。原位杂交显示，烧伤后主要脏器组织ＥＴ－１ｍＲＮＡ表达强度及阳性细胞数迅速增加；其表达峰值的次序为肾、肝、肺、心，且表达阳性细胞种类增加。这可能与内皮素发挥其强大的缩血管作用、调节血流再分布有关，对保证供给休克状态下重要器官的血流灌注有其有益的一面，但ＥＴ－１ｍＲＮＡ的过度表达则可能加重内脏器官的缺血缺氧性损害。     

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.     

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.     

Immunomodulation in Transplantation with Photopheresis

Abstract: Photopheresis is a technique in which peripheral blood mononuclear cells, in the presence of a photoacti-vatable compound, are exposed extracorporeally to ultraviolet A light and reinfused, inducing a host autoregula-tory immune response. Experimental work and ongoing clinical studies are helping to define the role of this novel, safe, and non-toxic immunomodulating technology in the field of transplantation.