霉酚酸酯对脓毒症肝损伤的保护作用

目的:探讨霉酚酸酯(mycophenolate mofetil,MMF)对脓毒症小鼠肝脏的保护作用。方法:将48只雄性Balb/c小鼠随机分为脓毒症模型组、MMF预处理[10 mg/(kg·d),2 d]的脓毒症模型组。两组分别于造模后1 h、6 h和24 h及假手术后检测丙氨酸转氨酶(alanine aminotransferase,ALT)水平并行肝脏HE染色及病理评分。采用Western印迹法检测自噬相关蛋白LC3Ⅰ/Ⅱ表达并观察7 d存活率。结果:与假手术组相比,脓毒症小鼠造模后6 h和24 h病理评分显著增高[(3.17±0.75)比(0.50±0.55)](P     

β-arrestin-2通过抑制自噬减轻小鼠肝脏缺血-再灌注损伤

目的探讨β-arrestin-2对小鼠缺血-再灌注(IR)肝脏自噬的影响及其在肝脏缺血-再灌注损伤(IRI)中的作用。方法采用β-arrestin-2野生型(WT)及基因敲除(KO)小鼠制作肝脏IR模型(70%肝脏缺血90 min后恢复肝脏血流)。实验分为4组:即WT小鼠假手术组(WT+Sham组)、WT小鼠IR组(WT+IR组)、KO小鼠假手术组(KO+Sham组)、KO小鼠IR组(KO+IR组),每组各18只。再灌注6、12、24 h收集各组小鼠血清和肝组织标本。通过检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平、肝组织苏木素-伊红(HE)染色和病理学分析判断肝脏损伤程度,用免疫组织化学(免疫组化)染色和蛋白免疫印迹法检测自噬关键蛋白轻链3(LC3)的表达、透射电子显微镜(透射电镜)观察肝组织中的自噬体来分析判断肝脏自噬活动情况。结果与Sham组相比,IR组再灌注后各时间点血清ALT、AST显著升高(均为P0.01),KO+IR组较WT+IR组升高更明显(均为P0.01)。肝组织HE染色显示,WT+Sham组和KO+Sham组再灌注后各时间点肝细胞形态、肝小叶结构正常;KO+IR组和WT+IR组再灌注后6 h肝细胞轻、中度肿胀,肝窦稍扩张,12 h肝细胞重度肿胀,炎症细胞浸润,片状损伤区域明显,24 h肝索排列趋于规则;与WT+IR组比较,KO+IR组再灌注后各时间点的损伤程度更严重和范围更大。免疫组化染色和蛋白免疫印迹法结果显示再灌注后6、12 h自噬关键蛋白LC3的表达呈上升趋势,24 h表达略有下降,其中KO+IR组的表达水平高于WT+IR组。肝组织透射电镜结果显示再灌注后各时间点IR组的自噬体数量均明显高于Sham组(均为P0.01),KO+IR组的自噬体数量较WT+IR组明显增多(P0.05)。结论β-arrestin-2可能通过抑制自噬来减轻小鼠肝脏IRI。     

去势后阻断自噬对大鼠前列腺细胞凋亡的影响

目的：探讨去势后阻断自噬对大鼠前列腺细胞凋亡的影响。方法 SD雄性大鼠72只随机分为3组：即假切对照组、去势组、去势＋硫酸羟氯喹处理组。各组大鼠分别于术后第1、3、7、10、14、21d随机抽取4只,完整取出前列腺组织。 HE染色观察大鼠前列腺组织形态学变化,电镜下观察前列腺微观结构、自噬和凋亡的变化,免疫组化SP法检测自噬受体蛋白P62和凋亡促进蛋白 Caspase－3在前列腺组织中表达。结果光镜下去势后大鼠前列腺体积逐渐缩小,腺上皮细胞逐渐萎缩,核染色加深,腺泡萎缩甚至闭塞,间质增生,加用羟氯喹处理后这一变化更加明显。电镜下观察去势后自噬小体的数量明显增加。免疫组化检测去势后自噬活性蛋白P62表达减弱,用羟氯喹处理后表达增强;凋亡促进蛋白 Caspase－3表达增强,用羟氯喹处理后表达进一步增强。结论去势后大鼠前列腺细胞自噬增加,自噬抑制剂羟氯喹可通过阻断细胞自噬增加大鼠细胞凋亡,自噬可能具有抗凋亡作用。     

阿仑膦酸钠治疗失神经骨骼肌萎缩的实验研究

目的通过观察阿仑膦酸钠(alendronate, ALN)对小鼠失神经骨骼肌萎缩肌肉组织中自噬信号通路相关蛋白LC3、Beclin-1和P62表达的影响, 探讨其治疗骨骼肌萎缩的分子生物学机制。方法使用随机数方法将30只雄性C57BL/6小鼠分为3组(每组10只):空白对照组, 暴露坐骨神经不切除;模型组, 暴露坐骨神经并切除;ALN组, 切除坐骨神经+ALN干预。造模阶段采用坐骨神经切断术建立失神经骨骼肌萎缩小鼠模型;干预阶段给予小鼠1 mg/kg ALN灌胃治疗。采用湿重称量法称量小鼠腓肠肌质量;采用肌球蛋白ATP酶染色区分肌纤维类型;采用HE染色观察各组腓肠肌肌纤维排列和横截面积, 并通过Image J进一步定量计算分析;行RT-qPCR、Western blotting和免疫组织化学染色检测各组腓肠肌组织中MHC、MuRF1表达以及LC3Ⅰ、LC3Ⅱ、Beclin-1和P62表达情况。结果与空白对照组比较, 模型组小鼠腓肠肌质量显著降低, 证明小鼠失神经骨骼肌萎缩模型造模成功。与模型组比较, ALN组小鼠腓肠肌质量明显升高。HE染色示模型组肌纤维排列松散, 肌纤维间出现较多蓝染...     

胶原凝胶复合骨髓间充质干细胞对小鼠 急性肝衰竭的疗效与机制研究

目的 探讨移植胶原凝胶复合骨髓间充质干细胞（bone marrow mesenchymal stem cells,MSCs） 对小鼠急性肝功能衰竭（acute liver failure,ALF）的治疗效果与机制。方法 105只雄性C57BL/6 小鼠随机 分为5组：对照组、ALF组、ALF+胶原凝胶组、MSCs组和胶原凝胶-MSCs组,每组21只。ALF组、ALF+ 胶原凝胶组、MSCs组和胶原凝胶-MSCs组采用腹腔注射D-氨基半乳糖苷（D-Gal）12 h后,分别于肝脏多 点注射200 μL PBS、200 μL胶原凝胶、1×106 MSCs和1×106胶原凝胶-MSCs。记录各组小鼠7 d存活率, 全自动生化仪检测肝功能水平,HE染色检测肝脏组织病理学改变,免疫组化检测肝细胞凋亡和增殖情况, 利用实时荧光定量PCR（RT-qPCR）检测肝脏炎症因子水平,Western blotting检测PI3K-AKT信号通路表达。 结果 扫描电镜示胶原凝胶与MSCs具有较好的相容性,动物活体成像检测显示胶原凝胶-MSCs移植的 信号强于单独MSCs移植的ALF小鼠。D-Gal处理后,胶原凝胶-MSCs组和MSCs组的小鼠生存率明显提高 （P＜0.05）,小鼠血清AST、ALT在胶原凝胶-MSCs组和MSCs组的小鼠明显优于ALF组和ALF+胶原凝胶 组（P＜0.05）,且肝功能指标明显改善,胶原凝胶-MSCs组要更优于MSCs组（P＜0.05）。 HE染色提示胶原 凝胶-MSCs组肝脏的病理改变（肝细胞坏死部位和范围）轻于MSCs组,Western blotting、Ki-67和cleavedCaspase3免疫组化结果显示,胶原凝胶-MSCs组肝细胞增殖能力强于MSCs组,同时肝细胞凋亡程度要低 于MSCs组,相应的胶原凝胶-MSCs组肝脏内IL-1β、IL-6、TNF-α、iNOS和CCL2等炎性因子水平也低于 MSCs组。且胶原凝胶-MSCs移植能明显激活肝脏内的PI3K-AKT通路。结论 胶原凝胶复合MSCs移植能 增强MSCs的肝脏定植能力,通过抑制细胞凋亡和促进细胞增殖减轻肝损伤,并调控AKT信号通路改善肝 细胞功能,因此胶原凝胶复合MSCs移植优于单纯MSCs移植治疗ALF。     

氯喹在小鼠肝脏热缺血-再灌注损伤中的保护作用

目的:研究氯喹对小鼠肝脏热缺血-再灌注损伤的保护作用,并探讨相关机制。方法:Balb/c小鼠建立肝脏部分热缺血-再灌注模型。氯喹组给予氯喹预处理,对照组给予等体积生理盐水。肝脏再灌注1、6、24 h后检测血清谷氨酸转氨酶(ALT)水平,HE染色检测肝脏病理学变化,荧光定量PCR检测炎症因子TNF-α和IL-6 m RNA水平,Western印迹检测肝脏TLR4及HMGB1表达。结果 :与对照组相比,氯喹组再灌注1、6、24 h血清ALT显著下降(P<0.05);肝细胞变性坏死、炎性细胞浸润显著减轻(P<0.01);血清TNF-α、IL-6含量显著降低(P     

HiPSC-MSC外泌体促进大鼠肝再生修复作用的研究

目的:探讨间充质干细胞(HiPSC-MSC)外泌体对大鼠肝切除70%后肝脏再生及修复的作用。方法:提取HiPSC-MSC外泌体,电镜观察并Western印迹检测表面标志物CD9、CD63和CD81表达。建立雄性SD大鼠70%肝切除模型,随机分为实验组及对照组。实验组在建模时外泌体-PBS溶液注入门静脉,对照组给予等量PBS。采用HE染色观察肝脏组织形态学改变,生化方法检测天冬氨酸转氨酶及谷氨酸转氨酶的水平,免疫组织化学检测增殖细胞核抗原Ki67的表达。结果:成功提取外泌体,透射电镜及表面标志物检测均符合。肝脏组织镜下显示,实验组术后1、3 d肝窦轻度扩张,较少炎性细胞浸润,少见坏死,坏死程度明显轻于对照组。实验组术后1、3、5 d血谷氨酸转氨酶和天冬氨酸转氨酶水平较对照组明显降低,其差异有统计学意义(P<0.001)。结论:HiPSC-MSC外泌体促进大鼠肝切除70%后肝再生及修复。     

苯甲酸雌二醇诱导不育小鼠睾丸中生精细胞增殖紊乱的研究

目的:探讨外源性雌激素苯甲酸雌二醇(EB)对诱导雄性不育小鼠中生精细胞增殖紊乱的影响。方法:60只雄性昆明小鼠随机分为3组,对照组肌肉注射150μl玉米油,EB处理组注射浓度分别为5、10 mg/kg的EB,隔天1次,持续4周。实验结束后取睾丸称其质量并计算睾丸指数;睾丸、附睾尾常规石蜡切片,HE染色;附睾尾制备精子悬液进行精子计数;免疫组化检测睾丸PCNA表达;qRT-PCR分析睾丸细胞周期蛋白A1、细胞周期蛋白B1、VASA、p53的表达变化;Western印迹检测p53及磷酸化p53蛋白表达。结果:与对照组相比,EB处理组小鼠睾丸指数显著下降[(0.56±0.09)%vs(0.43±0.08)%、(0.38±0.10)%,P0.05],精子悬液镜下观察未见精子,HE染色附睾管内未见精子;生精小管中精原细胞、初级精母细胞及支持细胞数量显著下降(P0.05)。免疫组化结果显示,与对照组相比,EB处理组生精小管中细胞PCNA阳性表达细胞数量显著下降(P0.05)。qRTPCR结果表明EB处理组PCNA、细胞周期蛋白A1、细胞周期蛋白B1、VASA mRNA表达与对照组相比显著下降(P0.05);p53表达随EB剂量升高而显著升高(P0.05)。Western印迹结果显示,与对照组相比,EB处理组p53及磷酸化p53蛋白表达水平显著升高,且存在剂量依赖效应,10 mg/kg组显著高于5 mg/kg组(P0.05)。结论:EB以剂量依赖的方式下调细胞周期相关因子表达抑制生精细胞的增殖,是导致雄性不育小鼠睾丸中生精细胞增殖紊乱的重要原因。     

17-β雌二醇对不同月龄大鼠成骨细胞雌激素受体β表达的影响

目的探讨17-β雌二醇对不同月龄大鼠成骨细胞雌激素受体β（ERβ）表达的影响。方法雌性大鼠颅盖骨经多次酶消化、反复贴壁法分离纯化培养得到大量纯净成骨细胞并进行形态学检查和碱性磷酸酶（ALP）染色;免疫组化法（SABC）进行雌激素受体染色;用10-8mol/L17-β雌二醇处理培养的成骨细胞,SDS-PAGE电泳和western blot法检测雌激素受体。结果成骨细胞碱性磷酸酶染色阳性率为90%以上。形态学检查符合成骨细胞的特征。免疫组化染色显示大鼠的成骨细胞存在雌激素受体β,且位于胞核内。Western blot结果表明,与对照组相比,处理组的各月龄大鼠雌激素受体β表达均有上调。结论17-β雌二醇能提高各月龄组大鼠成骨细胞雌激素受体β表达水平,不同月龄间上调水平不同,以4、8月龄组最为显著。     

维生素E治疗对老年雌性大鼠骨量、骨代谢以及自噬水平影响

目的观察维生素E对老年雌性大鼠骨量、骨代谢作用及自噬水平的影响。方法10只年轻雌性大鼠和20只老年雌性Sprague-Dawley大鼠被随机分为三组:对照组(10只年轻大鼠)、模型组(10只老年大鼠)和治疗组(10只老年大鼠)。在实验过程中,治疗组接受维生素E治疗。治疗12周后,通过Micro-CT和HE切片染色检测大鼠股骨骨密度(bone mineral density,BMD)和骨微结构变化;使用ELISA试剂盒检测血清中骨转换标志物水平的改变;通过蛋白质印迹检测维生素E对骨细胞自噬蛋白的影响。结果Micro-CT检测和HE切片染色表明维生素E治疗可以改善老年大鼠股骨干骺端骨密度和骨小梁微观以及微观参数[骨体积/总体积(BV/TV),骨小梁厚度(Tb.Th),骨小梁数(Tb.N)和骨小梁分离度(Tb.Sp)]。和模型组比较,治疗组骨吸收指标抗酒石酸酸性磷酸酶5b(TRACP-5b)水平明显降低,骨形成指标骨钙素(OC)水平明显增加;自噬相关蛋白LC3-Ⅱ/LC3-Ⅰ、Beclin1和Atg 5的蛋白质表达更高,p62表达显著降低;比较差异有统计学意义(P<0.05)。结论维生素E能够通过提高自噬水平和改善骨转换来保护老年雌性大鼠的骨量。     

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 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.     

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.