腹腔区域性血流阻断动脉内介入化疗对循环系统影响的实验研究

目的：研究腹腔区域性血流阻断动脉内介入化疗对机体循环系统的影响。对象与方法：16头幼猪分为两组,每组8头,分别行腹腔区域性血流阻断（Stop-flow,SF)及区域性血流阻断动脉内介入化疗（Stop-flow-Chemotherapy,SFC,MMC 0.2mg/kg)。术中监测心率（HR）、平均动脉压（MAP）、中心静脉压（CVP）、肺动脉压（PAWP）、心排量（CO）、外周静脉阻力（SVR）及混合血氧饱和度（SvO2)。结果：两组实验动物术中的血流动力学指标均有较明显改变。血流阻断及再通后心率、心排量、血压、外周静脉阻力和混合静脉血氧饱和度（SvO2) 有显著变化,阻断开放后PAWP有一过性升高,CVP术中无明显改变,血流再通20分钟左右上述指标均基本恢复至术前水平。SF与SFC两组间无明显差异。结论：腹腔区域性血流阻断动脉内介入化疗对循环系统有一定影响,但均在可控制范围,提示在临床应用是安全可靠的。     

区域性血流阻断动脉内介入化疗对腹腔脏器功能影响的实验研究

目的：观察区域性血流阻断动脉内介入化疗(stop-flowchemotherapy，SFC)对腹腔脏器功能的影响。对象与方法：对16头幼猪行腹腔区域性血流阻断动脉内介入化疗(SFC，MMC 0．2mg/kg)。术中、术后监测肝肾功能指标及超氧化物歧化酶(SOD)、丙二醛(MDA)及谷胱甘肽过氧化物酶(GHS—Px)等缺血再灌注指标。结果：SFC可引起动物肝功能轻度损害，但均可在2周内恢复；对肾功能无不良影响，也不会造成明显的组织脏器缺血再灌注损伤。结论：区域性血流阻断动脉内介入化疗对腹腔脏器功能无严重损害，提示其在临床应用是安全可靠的。     

肝脏血流阻断方法及评价

Hepatectomy is the main option of treatment for liver cancer,and how to control the blood loss is an important issue for the recovery of patients.Continuous hepatic vascular occlusion(Pringle maneuver)is the oldest and simplest way for vascular occlusion and still used in clinical practice.But continuous hepatic vascular occlusion often gives rise to postischemic reperfusion injury due to clamping the portal vein and the hepatic artery in the hepatic pedicle.So intermittent clamping or hemihepatic vascular occlusion is recommended in complex liver resections or for patients with liver cirrhosis.Total hepatic vascular exclusion has the advantages of occlusion of vascular inflow and outflow of the liver,and is mainly used for patients with tumors invading the caval veins.Major hepatic veins and limited inferior vena cava reconstruction has been also achieved under inflow occlusion with extraparenchymal control of major hepatic veins.It is crucial to know how to select the optimal methods of hepatic vascular occlusion according to the specific conditions.Focusing on this issue,we have reviewed and evaluated various methods and relevant researches in this paper.     

选择性肝脏血流阻断在儿童肝脏肿瘤切除术中的应用

目的探讨选择性肝脏血流阻断技术在儿童肝脏肿瘤切除术中的应用效果。方法回顾性分析采用选择性肝脏血流阻断技术行肝脏肿瘤切除的26例儿童肝脏肿瘤患者的临床资料。其中选择性第一肝门和第二肝门血流阻断5例,第一肝门和右肝静脉阻断17例,第一肝门和左中肝静脉阻断4例。结果所有患者术中出血量、输血量降低,患儿无死亡。总并发症发生率14.8%,平均住院天数9.6 d。结论选择性肝脏血流阻断技术是是一种适合儿童肝肿瘤的安全有效的肝血流阻断技术。     

HSP72在腹腔区域性血流阻断动脉介入化疗中对肝脏保护作用的实验研究

目的:观察阿霉素(DOX)诱导猪肝脏热休克蛋白72(以下简称HSP72)蛋白表达在腹腔内区域性血流阻断动脉内化疗(以下简称stopflow)过程中对肝脏的保护作用,并探讨其保护机制。方法:将12只健康杂交雌性幼猪随机分为两组,DOX组动物施行stopflow式介入化疗,术前24h以每公斤体重1mg经外周静脉注射DOX;NS组则注射生理盐水。分别检测肝脏组织中HSP72及NFκBp65亚基表达。检测外周血ALT及AST水平,肝脏活检进行组织形态学观察,以评价阻断前及阻断区域血循环再通后不同时间段中的肝脏损伤程度。结果:注射DOX后24h,可见肝脏HSP72蛋白呈强阳性表达,NS组肝脏NFκBp65表达阳性,且逐渐减弱;而DOX组动物肝脏组织NFκBp65呈阴性,血清ALT、AST水平低于NS组(P<0.05),组织形态学改变亦轻于NS组。结论:术前应用DOX可诱导肝脏HSP72蛋白表达,并通过抑制NFκB激活而减轻stopflow过程对肝脏的影响。     

NF-κB与肝脏缺血再灌注损伤的研究进展

核因子kappaB（NF-κB）是近年发现的重要的转录因子。研究表明,肝脏缺血再灌注时,NF-κB能够转录调节诸多编码炎症介质的基因。肝脏的缺血再灌注损伤是临床肝移植术后最常见的病理生理过程之一,许多细胞因子参与了这一过程,如TNF-α、IL-1、ICAM-1、INOS等,近来许多研究表明这些细胞因子都受NF-κB的基因调控。目前较为一致的看法是肝缺血再灌注损伤过程中氧自由基等产物激活NF-κB,促使TNF-α、ICAM-1和INOS mRNA表达增强,导致肝缺血再灌注损伤。就NF-κB和肝脏缺血再灌注损伤之间的联系和作用作一综述。     

肝血流局部阻断切肝与第一肝门血流阻断切肝对TNF-α的影响及意义

目的 :从生化角度就第一肝门血流阻断切肝与局部肝血流阻断切肝进行对比研究。方法 :将 30头体重为 (4 4 .7± 4 .3)kg的幼猪随机分两组 ,一组采用阻断第一肝门的方法切除部分肝脏组织 ,另一组采用本院设计的肝气囊止血带切除同样的肝组织。所有动物于切肝前、切肝后 5min、切肝后 30min ,取外周静脉血及门静脉血检测TNF α(tumornecrosisfactor,TNF α) ,并于切肝后 12h、2 4h、4 8h、72h及 7d取外周静脉血检测ALT及TNF α。结果 :两组止血效果相似 ,但阻断第一血流切肝与局部肝血流阻断切肝组相比 ,肝功能影响重 ,TNF α明显高于局部肝血流阻断组 (P <0 .0 0 1)。结论 :局部肝血流阻断切肝优于第一肝门血流阻断切肝。     

肝门区肿瘤切除中肝脏血流阻断方法的探讨

目的 探讨肝脏血流阻断技术在肝门区肿瘤切除中的合理应用.方法 回顾性分析2005年1月至2008年3月采用第一肝门阻断法(Pringle法)和常温下全肝血流阻断技术(NHVE)相结合切除16例肝门区肿瘤的临床资料,分析肿瘤和肝门区血管的毗邻关系、阻断次数、阻断时间、术中出血量、输血量、术后并发症等指标.结果 本组16例患者采用Pringle法与NHVE相结合技术切除肿瘤,Pringle法平均阻断(3.8±1.6)次,平均阻断时间(46.6±28.8)min;NHVE平均阻断(1.6±0.4)次,平均阻断时间(23.5±8.2)min;术中出血量平均(1250±320)ml,输血量平均(860±245)ml;术中修补下腔静脉损伤4例,肝静脉损伤2例,门静脉主干损伤2例;术后均有肝脏酶学指标、胆线素不同程度的升高,经保肝等治疗后恢复正常,未发牛肝功能衰竭等严重并发症.结论 Pringle法与NHVE技术分步结合使用可减少全肝血流阻断时间、增加肝门区肿瘤切除的安全性.     

入肝血流阻断与肝脏再生(文献综述)

本文综述近几年来肝脏再生的研究进展 ,简要介绍了入肝血流阻断对肝脏再生的影响及研究情况。     

Role of thromboxane in producing hepatic injury during hepatic stress

Hepatic injury after hepatic stress is caused by several mechanisms, including inflammatory reaction and microcirculatory disturbance. Levels of thromboxane, a vasoconstrictive eicosanoid, have been shown to increase in systemic circulation after different types of hepatic stress such as endotoxemia, hepatic ischemia-reperfusion, hepatectomy, liver transplantation, hemorrhagic shock and resuscitation, hepatic cirrhosis, and alcoholic liver injury. The production of thromboxane from the liver is also enhanced under these stresses, which may act on the liver in an autocrine or a paracrine fashion. Kupffer cells, resident hepatic macrophages, may be a major source of stress-induced thromboxane, although other cell types in the liver such as sinusoidal endothelial cells and hepatocytes may also produce this eicosanoid. Thromboxane induces hepatic damage through vasoconstriction, platelet aggregation, induction of leukocyte adhesion, up-regulation of proinflammatory cytokines, and induction of other vasoconstrictor release. In this regard, administration of cyclooxygenase inhibitor, specific thromboxane synthase inhibitor, and specific thromboxane receptor antagonists has been shown to protect from severe hepatic injury elicited by these hepatic stresses. Furthermore, blockade of Kupffer cell function by administration of gadolinium chloride showed salutary effects in preventing hepatic damage in bile duct ligation models. This review article summarizes the recent knowledge of the role of thromboxane in various types of hepatic stress and the effects of thromboxane inhibitors in these models.     

Intracerebral hemorrhage in a patient with isolated abdominal stop-flow infusion chemotherapy

A case of unresectable liver metastases in a patient with breast cancer is reported. Isolated abdominal perfusion chemotherapy was performed in the patient, a 48-year old woman who complained of severe abdominal pain despite receiving analgetic treatment. The perfusion was uneventful, but 3h later the patient showed dilated and light-fixed pupils. A cranial computed tomography scan revealed a massive intracerebral hemorrhage and intracerebral metastasis. Brain death developed and the patient died 26h after stop-flow perfusion. Based on this experience, any intracerebral metastasis should be considered as a contraindication for abdominal and pelvic stop-flow chemoperfusion.     

Study of blunt hepatic injury by ultrasonography

Sixty five consecutive patients with blunt hepatic injury were evaluated retrospectively to assess the clinical usefulness of emergency ultrasonography (US). In 30 patients before introduction of US, five patients (16.7%) were treated nonoperatively since they were hemodynamically stable with negative paracentesis. Another four hemodynamically stable patients were surgically treated due to positive paracentesis. After introduction of US, on the other hand, 17 out of 35 patients (48%) were successfully managed nonoperatively. Furthermore, US revealed small intraperitoneal bleeding and enabled conservative treatment of four hemodynamically unstable patients. There was no change in the management of central liver rupture or Makiya's type III injury. The number of nonoperatively managed cases of Makiya's types I and II increased from 1 to 7 after using US, and that of operative cases decreased from 21 to 12. Thus US was helpful to exactly assess the amount of intraperitoneal bleeding and successfully reduce the number of unnecessary laparotomy. We conclude that US provides useful information to decide early management of blunt hepatic injury.     

Uncommon left hepatic duct injury during laparoscopic cholecystectomy

Laparoscopic cholecystectomy is currently the gold standard in the treatment of symptomatic gallstones but has been shown to have a higher incidence of biliary tree lesions (0.3-1%) compared with reported traditional open approaches. Loss of three-dimensional view and of depth perception is the main limit of the laparoscopic approach, especially if particular risk factors are associated (e.g., postinflammatory fibrosis, anatomic variations). Moreover, inadequate training may justify the increase of biliary tract lesions. The authors describe a unique case of left hepatic duct clipped without section of the duct itself during an otherwise "easy" operation. At the reintervention, because of the favorable local condition, a reconstruction was possible after a small duct resection with a ductal-hepatic anastomosis over a T-tube. This was removed after 8 months because of the good patency of the biliary tree and the absence of cholestasys. A long-term follow-up is mandatory for a complete functional evaluation.     

Intraaortic stop-flow infusion: Pharmacokinetic feasibility study of regional chemotherapy for unresectable gastrointestinal cancers

Background: This study attempted to increase the exposure of gastrointestinal tract tissues to chemotherapy by prolonging the first pass of intraaortically administered drug by temporary occlusion of vascular structures. Methods: Bolus infusion of¹⁴C-labeled mitomycin C (MMC) mixed with unlabeled MMC was performed in dogs. Distribution of MMC in gastrointestinal tract tissues was studied under different types of major vessel occlusion. Three dogs with intravenous infusion constituted the control group. Vascular flow was controlled in four ways for 30 min: type I—stop-flow infusion (SFI) with clamping of the abdominal aorta above the celiac and below inferior mesenteric artery; type II—with additional clamping of the inferior vena cava above the diaphragm; type III with additional clamping of the portal vein in the hepatoduodenal ligament; and type IV—with surgical exclusion of nongastrointestinal branches of the aorta in addition to type II clamping. Results: Type II and IV produced a 3–10-fold increase in exposure to MMC of major gastrointestinal tissues as compared with intravenous infusion. Area under the curve ratios with type IV were most prominent in the following tissues: stomach, pancreas, liver, and mesenteric lymph node. Conclusion: Access of MMC to several gastrointestinal tissues was increased through SFI. Type IV infusion was the most effective. Tissue exposure to MMC was especially advantageous for stomach, pancreas, liver, and mesenteric lymph node.Presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

Breakdown of hepatic tight junctions during reoxygenation injury.

We investigated whether reoxygenation following anoxia increased biliary permeability and whether or not allopurinol had a protective effect. Isolated rat livers were perfused for 30 min in a one-pass system with buffer equilibrated with 100% nitrogen after stabilization, and then for 60 min with the oxygenated buffer. Hepatic tight junction permeability was assessed by quantifying the early appearance in the bile of horseradish peroxidase (HRP) injected with the perfusate. This early peak represents paracellular passage of HRP, whereas a later second peak results from transcellular passage. In the control livers, 7% of the total HRP passage (93 +/- 50 pg/g liver) was paracellular and 93% was transcellular. After 30 min of reoxygenation following anoxia, however, 516 +/- 20 pg/g liver of HRP passed paracellularly. Addition of allopurinol (5 micrograms/ml) to the perfusate from the start of perfusion reduced paracellular passage of HRP to 219 +/- 49 pg/g liver after anoxia and reperfusion (P less than 0.01). Allopurinol also reduced the cumulative lactate dehydrogenase (LDH) release during the first 30 min of reoxygenation from 2.1 +/- 0.3 x 10(4) to 1.4 +/- 0.4 x 10(4) units/g liver (P less than 0.01). Reduction of the anoxic period from 30 min to 25 min significantly reduced the change in tight junction permeability and the extent of cellular injury: Paracellular passage of HRP was 336 +/- 20 pg/g and LDH release was 0.7 +/- 0.1 x 10(4) units/g liver, both significantly lower than those at 30 min (P less than 0.01). No significant difference in hepatic ATP levels after 60 min of reoxygenation was noted among the experimental groups, but all had lower levels than the control group. The protective effect of allopurinol suggests that the mechanism of biliary reoxygenation injury involves free radical generation. Susceptibility of tight junctions suggests a pattern of injury similar to that involved in anoxic damage of the vascular endothelium.     

Ischemia-reperfusion injury of the human liver during hepatic resection

Haemorrhage during resection of the liver remains a significant threat to clinical outcome. Portal triad occlusion, with complete clamping of the hepatic inflow at the hepatoduodenal ligament, is a well-documented, safe, and useful means of alleviating this problem. Although this technique is effective in limiting blood loss, there is still controversy concerning the potential drawbacks of ischemia and subsequent reperfusion injury of the liver. This article highlights recent advances in our understanding of the clinical factors influencing ischemia-reperfusion injury of the liver, particularly in human patients. These factors include the cell components involved, the mechanisms that enable the human liver to tolerate long-term inflow occlusion, factors affecting clinical outcomes, and surgical and pharmacological techniques used to alleviate ischemia-reperfusion injury, including hypothermic hepatectomy.     

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     

Effects of N-acetylcysteine in hepatic ischemia-reperfusion injury during hemorrhagic shock

This article seeks to standardize an experimental model of liver ischemia-reperfusion in rats following hemorrhagic shock modulated by N-acetylcysteine (NAC). Twenty-seven adult Wistar rats were randomized into three groups: the HS-IR-Garm underwent hemorrhagic shock with selective hepatic ischemia followed by reperfusion; the HSIR + NAC-G, the same procedure plus NAC; and the control group, only venous catheterization. Blood was withdrawn for 10 minutes until MABP reached 35 mm Hg, which was maintained for 1 hour. The blood was then reinjected as required to maintain MABP at that level. Ringer's lactate solution was infused in a volume equivalent to three times the shed blood, over a period of 15 minutes. Half of the shed blood was reinfused over 5 minutes. HSIR + NAC-G received 150 mg/kg of NAC, during treatment of the shock, and again 10 minutes before reperfusion and continued for 30 minutes. Finally, both groups were subjected to 40 minutes of warm selective hepatic ischemia and reperfusion for 1 hour. Data were analyzed by nonparametric tests (P < or =.05). Liver enzyme levels were higher in HS-IR-G (DHL = 6094 +/- 1688, AST = 746 +/- 175, and ALT = 457 +/- 90) than in HSIR + NAC-G group (DHL = 2920 +/- 284, AST = 419 +/- 113, and ALT = 253 +/- 26). The values in the control group were lower than both experimental groups (DHL = 965 +/- 173, AST = 163 +/- 42, and ALT = 82 +/- 28). Our data showed that liver ischemia-reperfusion injury following hemorrhagic shock produces important hepatic damage and that NAC reduces injury in this rat model.