体外静脉-静脉转流在62例原位肝移植手术中的应用

目的：研究体外静脉转流在原位肝移植手术的应用，以便正确预防和处理体外静脉转流引起的病理生理变化。方法：62例原位肝移植患者在无肝期均采用体外静脉转流；转流中加强监测血流动力学、凝血功能、血气及血生化；转流中均使用离心泵。结果：(1)无肝期应用体外静脉转流对无肝期的血流动力学及新肝期的循环再灌注起到有效调控作用。(2)手术各期无明显酸碱紊乱，仅转流后有轻微酸中毒。(3)凝血功能有不同程度紊乱。(4)离心泵和肝素涂抹管路的应用，使血液有形成分破坏少，围术期出血量明显减少。结论：无肝期采用体外静脉转流，有助于稳定循环，无明显酸中毒及高血钾，转流中及转流后应加强对凝血和血气的监测和调控。     

去甲肾上腺素对非静脉转流下原位肝移植术血流动力学的影响

<正>晚期肝硬化患者血流动力学多数呈高动力血流状态。麻醉管理的关键是克服脏器因低血管阻力所致的低灌注压性损害[1]。在无肝期使用静脉-静脉转流技术,能对经典原位肝移植术血流动力学起很大的稳定作用。随着手术技术的成熟,笔者对52例肝移植手术中12例在无静脉转流下完成。本文着重探讨去甲肾上腺素对非静脉转流下经典式肝移植术围术期血流动力学的影响。     

经典非转流肝移植再灌注期血流动力学改变与对策

原位肝移植手术再灌注期血流动力学容易发生波动,而在非转流经典术式中更容易发生,本研究对25例原位经典术式非转流肝移植患者再灌注期血流动力学变化进行观察分析,现将结果报告如下.     

非静脉转流下原位肝移植围手术期循环和电解质变化的观察

目的:观察非静脉转流下,经典原位肝移植病人围术期电解质浓度和血流动力学变化。方法:9例经典原位肝移植病人在非静脉转流下,行气管插管静吸复合麻醉,术中经颈静脉双腔管持续监测CVP,桡动脉置管监测ABP。于手术各期定时抽取桡动脉血行血气分析,测定钠、钾、钙浓度。常规持续监测HR,SpO2,PETCO2及体温。结果:本组9例围手术期血钙持续偏低,无肝期和再灌注前期尤为明显。无肝期前期(5 m in)及再灌注前期(5 m in)血钾轻度上升,无肝期中期(30 m in)及再灌注中期(30 m in)血钠轻度上升,但极少超出正常范围,病人血流动力学稳定后逐渐恢复诱导后水平。进入无肝期后,大部分病人血压一过性明显下降,其余时间段均较平稳。结论:非静脉转流原位肝移植,无肝期及再灌注期应注意纠正低血钙,无肝期前期(5 m in)及再灌注前期(5 m in)应警惕高血钾发生。进入无肝期前应适当扩容,无肝期中应用血管活性药物维持血压,及时根据病人失血量及血球压积补充血容量,尽可能维持围术期循环稳定,防止再灌注前期严重酸中毒的发生。     

非转流情况下肝移植术中血流动力学的监测治疗（附5例报告）

2002年9月～2003年4月,我院开展了4例同种异体改良背驮式肝移植术和1例异体原位肝移植术,术中不进行股静脉-腋静脉转流,而采用非转流的血流动力学控制,现将麻醉及术中血流动力学的监测治疗报道如下.     

原位肝脏移植一例麻醉处理

１９９４年５月１０日我院在动物实验的基础，成功地完成了１例同种原位肝脏移植术，受者为晚期肝硬化合并门静脉高压症患者，采用无肝体外静脉转流术，即采用进口离心式生物泵进行无肝期门静脉、右股静脉向左腋静脉的转流，此方法在很大程度上防止阻断门静脉及下腔静脉后循环的非生理状态，而对血流动力这和肾功能影响甚微，术后无手术并发症发生，增加了围手术期的安全性，术后病人顾活至今，现将手术期麻醉的监测，处理等作一简介     

背驮式同种异体原位肝移植的麻醉管理

目的 探讨行背驮式原位肝移植围手术期的麻醉管理特点.方法 8例行背驮式同种异体原位肝移植术的终末期肝病、肝癌患者,ASAⅢ～Ⅳ级.采用静吸复合全身麻醉,监测术前、无肝前期、无肝期、再灌注期(新肝早期)及新肝期的心率(HR)、平均动脉压(MAP)、中心静脉压(CVP)、股静脉压、肺动脉压(PAP)、肺毛细血管楔压(PCWP)、凝血功能及血气和生化功能指标,并精确记录术中的尿量和出入量.根据背驼式原位肝移植各期的不同特点,对血流动力学、酸碱平衡、电解质、凝血功能、体温、肾功能进行综合调控和保护.结果 围麻醉期8例成功,康复出院6例,术后死亡2例(抢救性肝移植),出院后死亡1例(肝癌复发).无肝前期、无肝期HR与术前相比有较明显的增快,而在再灌注期则明显降低;血流动力学在无肝前期、无肝期和再灌注期出现明显改变,尤以再灌注期最为显著.酸碱平衡在无肝期和再灌注期出现明显改变,以再灌注期最明显.从无肝前期至再灌注期凝血功能进一步紊乱,尤其在无肝期和再灌注期.再灌注期血钾和术前相比有明显增高,血钙则出现明显的降低;再灌注期体温下降明显.结论 提高原位肝移植麻醉安全性的关键是及时、有针对性的对血流动力学、凝血功能、酸碱平衡、电解质、体温、肾功能进行综合调控和保护.     

原位肝移植患者术中血流动力学及血生化变化与处理

肝移植是治疗终末期肝脏疾病的一种有效方法，但因晚期肝病的病理生理特征及肝移植手术的巨大创伤和对机体的干扰，临床上主要表现为血流动力学的剧烈波动和内环境与凝血功能紊乱，并累及重要器官的功能。我院自2004-01-2005-05进行成人原位经典肝移植（OLT）20例。本文着重讨论经典非静脉一静脉转流原位肝移植术中血流动力学、酸碱及电解质变化及麻醉处理。     

原位肝移植围术期液体管理的体会

目的探讨原位肝移植时围术期液体的管理。方法28例肝移植患者选择全麻。气管内插管。静吸复合,均采用非静脉-静脉转流技术。根据肝移植各期的生理特点分别进行液体管理。无肝前期．蹦为出血较多。定期监测Hb．Hct、白蛋白及时补全血。血细胞、白蛋白及胶体液,及时维持无肝前期末时CVP 9cm H2O以上。无肝期。此期因门腔静脉阻断,防止新肝期时门腔静静脉开放时回心血量猛增,对心肺负荷加重,此期增应尽最控制液体,应补充血液、血浆为主。新肝期时门腔静脉开放,回心血量猛。进行容量控制外,根据出血情况,监测CVP、PAWP的情况,必要时用速尿、甘露醇排除多余体液。结果28例原位肝移植均能安全进行手术,无因容量负荷原因而导致并发症。结论良好的围术期液体管理是原位肝移植的保证。     

非体外静脉转流原位肝移植受体术中促炎细胞因子的变化

目的研究观察非静脉转流下原位肝移植患者术中促炎细胞因子TNF-α和IL-6水平的动态变化,并探讨其产生的原因,为预防和治疗肝移植围术期炎性反应提供理论基础。方法连续完成的40例终末期肝病患者接受首次原位肝移植术,应用气管插管异氟醚吸入复合异丙酚、芬太尼、维库溴铵维持麻醉,无肝期未采用体外静脉-静脉转流。常规应用乌司他丁和抑肽酶。分别于麻醉后切皮前（T0）、无肝期前60分钟（T1）、无肝期30分钟（T2）、新肝期15分钟（T3）、术毕（T4）共5个时点抽取桡动脉血,放免法测定血浆LL-6、TNF-α浓度。结果肝移植患者术中各阶段,两种促炎细胞因子水平呈升高趋势。与T0（切皮前）比较,IL-6水平无肝前期（T1）就显著升高（P〈0.05）,新肝期（T3）升高至高峰（P〈0.01）,它的变化要早于TNF-α;TNF-α的水平无肝前期（T1）变化不大（P〉0.05）,无肝期（T2）开始上升,新肝期（T3）上升至高峰（P〈0.01）。结论在非静脉转流原位肝移植术中不同阶段,促炎细胞因子反应水平不同,在新肝期促炎细胞因子水平上升至高峰。肝缺血、再灌注损伤是全身炎性反应的主要原因。常规剂量应用乌司他丁和抑肽酶不能完全抑制肝移植患者术中的炎性反应。     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.