胆道梗阻后肝脏自由基损伤及粉防己碱保护作用的实验研究

目的　观察胆道梗阻后肝脏的自由基损伤和粉防己碱（ Ｔｅｔ） 的保护作用。方法　复制大鼠胆道梗阻模型,每日给予 Ｔｅｔ ３０ ｍｇ／ｋｇ 体重灌胃,动态观测肝组织丙二醛（ Ｍ Ｄ Ａ） 和超氧化物歧化酶（ Ｓ Ｏ Ｄ） 含量及血清 Ｔ Ｂｉｌ、 Ａ Ｌ Ｔ、 Ａ Ｌ Ｐ、 Ｇ Ｇ Ｔ 含量。结果　胆道梗阻后,血清 Ｔ Ｂｉｌ、 Ａ Ｌ Ｔ、 Ａ Ｌ Ｐ、 Ｇ Ｇ Ｔ 水平逐渐升高,肝组织 Ｍ Ｄ Ａ 含量逐渐升高, Ｓ Ｏ Ｄ 逐渐减少,各梗阻组与对照组比较, Ｐ＜ ０ ．０５ 。各 Ｔｅｔ 治疗组与同时相梗阻组比较,血清 Ｔ Ｂｉｌ、 Ａ Ｌ Ｔ、 Ａ Ｌ Ｐ、 Ｇ Ｇ Ｔ 水平下降（ Ｐ＜ ０ ．０５） ;肝组织 Ｍ Ｄ Ａ 含量减少（ Ｐ＜０ ．０１） , Ｓ Ｏ Ｄ 含量升高（ Ｐ＜ ０ ．０５） 。肝组织 Ｍ Ｄ Ａ 含量与血清 Ａ Ｌ Ｔ、 Ａ Ｌ Ｐ 含量变化呈明显正相关,ｒ 值分别为０ ．９４９ 和０ ．８４３（ Ｐ＜ ０ ．０１） 。结论　自由基损伤可能是胆道梗阻导致肝损害的重要机制之一, Ｔｅｔ对胆道梗阻所致肝损害有明显保护作用。     

胆道梗阻后肝细胞线粒体钙含量变化和肝脂质过氧化？…

为了解胆道梗阻对肝脏的损害机理,在复制大鼠胆道梗阻模型基础上,分离肝细胞线粒体,动态检测肝细胞线粒体含量,肝组织ＭＤＡ,ＳＯＤ含量,血清Ｔ－Ｂｉｌ,ＡＬＴ,ＡＬＰ及ＧＧＴ含量。结果：肝细胞线粒体钙含量,肝组织ＭＤＡ含量和血清Ｔ－Ｂｉｌ,ＡＬＴ,ＡＬＰ及ＧＧＴ水平均随梗阻时间延长而逐渐升高（Ｐ〈０．０５）,肝组织ＳＯＤ含量则逐渐减少（Ｐ〈０．０５）;肝细胞线粒体钙含量与肝组织ＭＤＡ含量,血清ＡＬＴ水     

抗肿瘤坏死因子抗体和头孢噻甲羧肟对急性胆道感染肝损害的保护作用

在急性胆道感染大鼠模型上检测血浆肿瘤坏死因子（ＴＮＦ）、内毒素（ＥＴ）水平及血清谷丙转氨酶（ＡＬＴ）活性；观察肝组织结构和超微结构，抗ＴＮＦ单克隆抗体（ＴＮＦ－ＭＡｂ）和头孢噻甲羧肟的保护作用，结果显示：急性胆道感染组血浆ＴＮＦ、ＥＴ水平显著升高，血清ＡＬＴ活性也显著升高，肝组织病理变化明显；ＴＮＦ－ＭＡｂ与头孢噻甲羧肟保护组血浆ＴＮＦ，ＥＴ水平及血清ＡＬＴ活性显著下降，肝组织病理变化较轻，结果提示ＴＮＦ是急性胆道感染肝损害的重要介质；ＴＮＦ－ＭＡｂ和头孢噻甲羧肟对胆道感染肝损害有保护作用。     

免疫吸附清除肿瘤坏死因子-α对内毒素休克时肾功能的保护

目的观察免疫吸附特异性清除循环肿瘤坏死因子－α（ＴＮＦ－α）对内毒素休克时肾功能的影响，并探讨其可能的机制。方法给新西兰白兔一次性静注内毒素８．０×１０９ｃｆｕ／ｋｇ，１小时后经抗ＴＮＦ－α单克隆抗体亲和免疫吸附柱进行血液灌流２小时，观察血压、血浆ＴＮＦ－α活性、一氧化氮（ＮＯ）和内皮素－１（ＥＴ－１）含量、血浆丙二醛（ＭＤＡ）含量和全血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活力、肾组织中ＭＤＡ含量和超氧化物歧化酶（ＳＯＤ）活力及肾功能等的变化。结果免疫吸附治疗后，血浆ＴＮＦ－α水平迅速下降，低血压状态明显改善，ＮＯ、ＥＴ－１和氧自由基的生成显著减少，肾功能损害明显减轻，动物存活率提高。结论免疫吸附特异性清除循环ＴＮＦ－α可减轻内毒素休克时肾损害的发生，明显改善肾功能。     

胆道梗阻后肝细胞线粒体钙含量变化和肝脂质过氧化损害的实验研究

为了解胆道梗阻对肝脏的损害机理,在复制大鼠胆道梗阻模型基础上,分离肝细胞线粒体,动态检测肝细胞线粒体钙含量,肝组织ＭＤＡ、ＳＯＤ含量,血清ＴＢｉｌ、ＡＬＴ、ＡＬＰ及ＧＧＴ含量。结果：肝细胞线粒体钙含量、肝组织ＭＤＡ含量和血清ＴＢｉｌ、ＡＬＴ、ＡＬＰ及ＧＧＴ水平均随梗阻时间延长而逐渐升高（Ｐ＜０．０５）,肝组织ＳＯＤ含量则逐渐减少（Ｐ＜０．０５）;肝细胞线粒体钙含量与肝组织ＭＤＡ含量、血清ＡＬＴ及ＡＬＰ含量变化呈明显正相关,ｒ分别为０．９６７、０．９２４和０．９１９（Ｐ＜０．０１）;肝组织ＭＤＡ含量与血清ＡＬＴ和ＡＬＰ含量变化呈明显正相关,ｒ分别为０．９４９和０．８４３（Ｐ＜０．０１）。结论：肝细胞线粒体钙超载和脂质过氧化损伤密切相关,在胆道梗阻所致肝损害过程中起重要作用。     

抗肿瘤坏死因子抗体和头孢噻甲羧肟对急性胆道感染肝损害的保…

在急性胆道感染大鼠模型上检测血浆肿瘤坏死因子（ＴＮＦ）、内毒素（ＥＴ）水平及血清谷丙转氨酶（ＡＬＴ）活性；观察肝组织结构和超微结构，抗ＴＮＦ单克隆抗体（ＴＮＦ－ＭＡｂ）和头孢噻甲羧肟的保护作用，结果显示：急性胆道感染组血浆ＴＮＦ、ＥＴ水平显著升高，血清ＡＬＴ活性也显著升高，肝组织病理变化明显：ＴＮＦ－ＭＡｂ与头孢噻甲羧肟保护组血浆ＴＮＦ、ＥＴ水平及血清ＡＬＴ活性显著下降，肝组织病理变化较轻，结果提     

烧伤并发内毒素血症早期肝损害与TNF-α mRNA表达的实验研究

目的观察ＴＮＦαｍＲＮＡ及其蛋白的组织分布和细胞定位,探讨烧伤并发内毒素血症早期肝损害的发生机理。方法选用２０％Ⅲ度ＴＢＳＡ烧伤大鼠合并腹腔内毒素（ＬＰＳ）注射造成烧伤复合内毒素血症肝损害模型,采用光镜,电镜及免疫组化原位杂交染色观察大鼠肝脏的形态功能变化、血清ＴＮＦα含量变化、肝组织ＴＮＦα和ＴＮＦαｍＲＮＡ的细胞定位及其分布。结果烧伤复合内毒素血症组,光镜下主要表现肝窦反应,枯否细胞（ＫＣｓ）激活与增生以及肝细胞（ＨＣｓ）变性坏死等;电镜下主要表现肝窦内血小板聚集、纤维素沉积与中性粒细胞（ＰＭＮｓ）扣押以及ＫＣｓ、肝细胞退变溶解等。血清丙氨酸氨基转氨酶（ＡＬＴ）显著升高（Ｐ＜０．０１）和白蛋白（ＡＬＢ）轻度下降。组织ＴＮＦα主要定位于肝窦内皮细胞（ＳＥＣｓ）、ＫＣｓ。ＴＮＦαｍＲＮＡ主要定位于ＫＣｓ、ＰＭＮｓ、巨噬细胞（ＭＰｓ）。而在单因素组主要特点为病变程度轻,肝功能损害不明显,血清ＴＮＦα峰值滞后以及组织ＴＮＦα和ＴＮＦαｍＲＮＡ表达相对较弱等。结论ＴＮＦα是参与烧伤复合内毒素血症早期肝脏损害的重要细胞因子。     

心脏瓣膜置换术围术期动脉血及冠脉血TNF-α、SOD、LPO及CK-MB的变化

目的 观察进行体外循环（ＰＢ）病人围术期动脉血和冠脉血肿瘤坏死因子（ＴＮＦ－α）、超氧化物歧化酶（ＳＯＤ）、脂质过化物（ＬＰＯ）及肌酸激酶－ＭＢ（ＣＫ－ＭＢ）的变化。方法 １３例病人分别于ＣＰＢ前、升主动脉开放后５ｍｉｎ、３０ｍｉｎ、术毕、术后６ｈ、术后１８ｈ采集动脉和冠状窦血样本,测定血浆ＴＮＦα、ＬＰＯ的浓度及ＳＯＤ、ＣＫ－ＭＢ的活性和动脉血气,测算不同时间点的肺泡动脉氧分压差（ＰＡ－ａＤＯ２）,心肌ＴＮＦ－α的净释出量（冠状窦内血液ＴＮＦα含量减去动脉血含量）。结果 血液的ＴＮＦα水平在开放升主动脉后至术毕前明显增高（Ｐ〈０．０５）,ＣＰＢ期间心肌ＴＮＦα净释出量明显增高（Ｐ〈０．０５）;ＬＰＯ在开放升主动脉后明显升高且持续到术后６ｈ（Ｐ〈０．０５）,其峰值在开放升主动脉后５ｍｉｎ;ＳＯＤ含量逐渐下降并在     

利多卡因对兔内毒素性肺损伤后早期的治疗作用

目的：探讨利多卡因对兔内毒素性肺损伤后早期的治疗效应。方法：２４只大耳白兔随机分为对照组、内毒素（ＥＴ）致病组、ＥＴ致病加利多卡因治疗组。分别用酶联免疫法和硫代巴比妥酸反应法测量血浆和支气管肺泡灌洗液（ＢＡＬＦ）肿瘤坏死因子（ＴＮＦα）和丙二醛（ＭＤＡ）含量。结果：利多卡因治疗组于静注ＥＴ后３、５小时血浆和ＢＡＬＦ中ＴＮＦα和ＭＤＡ含量、肺湿干重比值、ＢＡＬＦ中性粒细胞数、白蛋白、Ｃ３ａ、Ｃ５ａ均显著低于ＥＴ致病组。提示利多卡因抑制肺内补体激活和中性粒细胞在肺内聚集，减轻脂质过氧化反应和炎症介质释放。结论：利多卡因对内毒素性肺损伤后早期有治疗作用。     

1,6—二磷酸果糖对内毒素休克犬TNF,MDA,SOD的影响

目的：观察１，６－二磷酸果糖对内毒素休克犬血浆ＴＮＦ，ＭＤＡ水平和ＲＢＣ－ＳＯＤ活性的影响，为ＦＤＰ治疗ＥＴ休克提供实验依据。方法：１２只犬随机分成两组，内毒素休克组和内毒素休克１，６－二磷酸果糖治疗组，每组６例，外周静脉注射灭活大肠杆菌３０分钟、９０分钟后、ＦＤＰ组输入７．５％ＦＤＰ３７５ｍｇ／ｋｇ，ＥＴ组输入等容量平衡盐液。注ＥＴ前及注后２、４、６、８小时测ＣＯ及血浆ＴＮＦ、ＭＤＡ水平和ＲＢＣ     

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.