肝切除时门静脉血部分动脉化的研究

目的 研究犬门静脉血部分动脉化的肝保护作用。方法 建立大保留肝（占全肝６０％）暂时性血流阻断、肝固有动脉切断并切除未阻断肝的急性肝衰模型（对照组）,并行肝总动脉与胃十二指肠静脉吻合（Ａ－Ｐ组）,观察生存率并定时测定丙氨酸转氨酶（ＡＬＴ）、动脉血酮体比（ＡＫＢＲ）及肝动脉脉、门静脉血气分析。结果 对照组７天生存率为３７．５％,Ａ－Ｐ组均较差异有非常显著性（Ｐ〈０．０１）,门静脉和肝静脉血氧分压均较术     

Administration of rhHGF-activator via portal vein stimulates the regeneration of cirrhotic liver after partial hepatectomy in rats

BACKGROUND/AIMS: Cirrhotic liver has less ability to regenerate than normal liver, but it can produce the precursor of hepatocyte growth factor (proHGF) similarly to normal liver after resection. Studies were performed to examine whether the exogenous administration of recombinant human (rh) HGF-activator converts proHGF to biologically active (mature) HGF, inducing an enhancement of liver regeneration in cirrhosis. MATERIALS AND METHODS: Rats with liver cirrhosis were treated by 45% partial hepatectomy, and rhHGF-activator or vehicle was injected via the portal vein 24 h after resection. Liver injury and its regeneration, the conversion of proHGF to mature HGF, and the activation of its signal through HGF receptor (c-Met) were analyzed. RESULTS: rhHGF-activator improved the recovery of liver function after resection in cirrhotic liver as compared with the control group. rhHGF-activator also enhanced the proliferating cell nuclear antigen labeling index and liver regeneration rate. rhHGF-activator converted the proHGF to mature HGF, showing the maximal effect at 10 min after injection, which was followed by tyrosine phosphorylation of insulin receptor substrate (IRS)-1, and the association of IRS-1 with c-Met and phosphatidylinositol 3-kinase. CONCLUSIONS: Results demonstrate that the administration of rhHGF-activator stimulates the recovery of liver function and regeneration after resection in cirrhotic liver through the activation of proHGF and its intracellular signal. It may be potentially useful treatment for patients with liver cirrhosis.     

Effects of mitochondrial lipoperoxidation on liver regeneration after partial hepatectomy of the cirrhotic rat liver

Lipoperoxide levels in mitochondrial fraction and mitochondrial respiratory activity during hepatic regeneration were studied serially in normal (N) and cirrhotic (C) rats following one-third (I) or two-third (II) partial hepatectomy. Recovery of liver weight after 14 days was about 90% in each group except C-II group, in which it was 71.3%. ATP synthetic activity (ATP-S) was always higher in N-II group than N-I which reached maximum on the first postoperative day (POD) and returned to the preoperative levels on the 14th POD. Lipoperoxide peak value of N-II group was obtained sooner than that of N-I group, in addition the peak value of N-II group was higher than that of the N-I group. ATP-S of C-II group reached maximum levels on the third POD and thereafter decreased progressively. In contrast, ATP-S of C-I group returned to preoperative level on the 14th POD. Peak lipoperoxide levels were obtained on the first POD in both groups, but that of C-II group was 1.6 times higher than that of C-I. Moreover, it was observed that inhibition of lipoperoxidation by alpha-tocopherol administration improved respiratory activity significantly. From these results it can be said that hepatectomy-induced lipoperoxidation in massive resection of the cirrhotic liver may inhibit activation of mitochondrial respiration and hepatic regeneration.     

扩大肝部分切除术后入肝门静脉动脉化对大鼠血流动力学的影响

目的对大鼠行扩大肝部分切除术后利用右肾动脉行入肝门静脉动脉化加门腔分流术,研究该术式对大鼠门静脉血流动力学的影响。方法 Sprague-Dawley大鼠130只,分为A组(动脉化组)47只,行70%扩大肝部分切除术后,用右肾动脉行门静脉动脉化加门腔分流术;B组(肝切组)43只,行70%扩大肝部分切除及右肾切除,阻断门静脉10min;C组(对照组)40只,仅行右肾切除及门静脉主干游离。分别于术后第2、7、14、28天检测门静脉压力、内径和血流量。结果 A组及B组手术成功率分别为85.1%和93.0%,差异无统计学意义,C组手术成功率100%。术后各时间点A组与B、C组比较,入肝门静脉压力、门静脉内径、血流速度和入肝血流量变化均较后两组更明显(P0.01);A组入肝门静脉压力随时间推移有下降趋势,于术后第14天(12.7±0.7)cmH2O达到稳态,与术后第28天(12.4±0.6)cmH2O比较,差异无统计学意义;而A组门静脉内径、血流速度和入肝血流量在术后各时间点间相比差异无统计学意义。B组术后门静脉血流速度均较C组增快(P0.05),门静脉血流量在术后14～28d较C组增加(P0.05)。结论大鼠扩大肝部分切除术后行入肝门静脉动脉化模型稳定可靠,手术成功率理想,动脉化术后门静脉压力明显升高,门静脉内径出现扩张以适应压力变化,入肝血流量明显增加。门静脉血流动力学指标在术后早期即发生改变并取得稳态。     

门静脉部分动脉化对大鼠肝部分切除后肝脏的影响

目的探讨门静脉部分动脉化对部分肝切除大鼠肝脏的影响。方法将48只SD大鼠分为肝部分切除术后非门静脉动脉化组及门静脉动脉化组。动态观察术后2，6，12h血清ALT，AST，以及肝组织中ATP，ADP，AMP含量的变化，并计算EC值；同时取肝组织行病理组织学检查。结果（1）与非动脉化组比较，动脉化组血清AST和ALT在术后2h无差异（P〉0．05），术后l2h动脉化组血清AST和ALT动脉化组明显降低（分别为P〈0.01及P〈0.05）。（2）动脉化组较非动脉化组术后各时点肝组织ATP和Ec均有明显增加（分别为P〈0.01及P〈0．05）。（3）非动脉化组肝组织病理变化随着缺血时间延长而加重；动脉化组病理变化较轻。结论门静脉部分动脉化在一定程度上可以减轻大鼠部分肝切除并肝动脉离断后的肝损害，改善肝细胞的能量代谢。     

Experimental study of partial arterialization of the portal vein on the dearterialized liver

The influence of hepatic arterial obstruction on the hepatic circulation and tissue metabolism was studied between animals with and without partial arterialization of the portal vein. Mongrel dogs were divided into these groups: a group in which the collaterals to the liver were obstructed and the hepatic artery was dissected (hepatic artery ligated group); two groups in which an extracorporeal femoral artery-portal vein shunt was produced, and blood was sent by a Biopump at a rate of 100 or 200 ml/min (100 ml/min and 200 ml/min portal arterialized groups). The hepatic artery ligated group showed CO2 accumulation and acidosis in hepatic venous blood, reduction of oxygen supply, increase of oxygen consumption and marked increase of GOT and GPT. In the portal arterialized groups, sufficient oxygenation of portal blood was noted, and the oxygen demand and supply and tissue metabolism were kept approximately normal. The optimum flow rate for partial arterialization of the portal vein seemed to be 100 ml/min. At the flow rate of 200 ml/min, the original portal blood was reduced, leading to portal hypertension and increase of GOT and GPT. These results indicate that partial arterialization of the portal vein effectively preserves the liver function during the operation and in the early period after dissection of the hepatic artery.     

Protective effect of portal vein arterialization in acute liver failure induced by hepatectomy in normal and fatty liver rat

AIM: We sought to determine whether an additional supply of oxygenated blood achieved by partial portal vein arterialization (PPVA) was protective on normal or fatty liver (FL) in rats with acute liver failure (ALF) induced by hepatectomy. METHODS: Sprague-Dawley rats with normal or FL were segregated either to receive or not to undergo PPVA after hepatectomy. FL was induced by feeding a choline-deficient diet (5 days). PPVA was performed by anactamasing the left renal artery to the splenic vein with a stent following a left nephrectomy and splenectomy; the control rats underwent left nephrectomy and splenectomy only. Liver injury was evaluated by the serum alanine aminotransferase (ALT) level. The animals were sacrificed at 24 hours, 48 hours, and 7 days to collect blood and liver tissue samples for biochemical analysis. The 7-day survival was assessed in separate experimental groups. RESULTS: PPVA significantly increased Po2 and oxygen saturation in the portal blood compared to non PPVA rats. PPVA significantly improved the 7-day survival compared with controls in both groups: hepatectomy of normal liver (90% vs 30%) and hepatectomy of FL (75% vs 25%). Serum ALT levels were slightly lower in the PPVA groups compared with the non-PPVA groups without a significant difference. Prothrombin activity decreased soon after hepatectomy in the normal and the FL liver groups but recovered rapidly thereafter without differences between the PPVA and non-PPVA treated animals. CONCLUSION: An additional supply of arterial oxygenated blood through a PPVA promotes rapid resolution of ALF after partial hepatectomy in rats with normal or fatty livers, significantly improving 7-day survivals compared to hepatectomy controls.     

Beneficial effects of arterialization of the portal vein on extended hepatectomy

BACKGROUND: Extended hepatectomy may result in postoperative liver failure. The aim of this study was to evaluate the effects of arterialization of the portal vein on oxygen supply, hepatic energy metabolism and liver regeneration after extended hepatectomy. METHODS: Portal haemodynamics were evaluated 0 or 10 days after arterialization of the portal vein in three experimental groups: 85 per cent partial hepatectomy, 85 per cent partial hepatectomy 10 days after arterialization of the portal vein and 85 per cent partial hepatectomy 10 days after ligation of the hepatic artery. Survival rates, weight of the regenerating liver, levels of adenine nucleotides and hepatic energy charge were assessed. RESULTS: Arterialization of the portal vein caused a significant increase in partial pressure of oxygen and oxygen saturation. Portal blood flow 10 days after arterialization was significantly increased. Survival rate and weight of the regenerating liver in the group with arterialization of the portal vein were significantly higher than those in the other two groups. The group with arterialization of the portal vein showed the highest levels of adenosine 5'-triphosphate. CONCLUSION: The increase in portal blood flow and oxygen supply produced by arterialization of the portal vein has beneficial effects on hepatic energy metabolism and liver regeneration, and leads to improved survival after experimental extended hepatectomy.     

门静脉动脉化对大鼠肝脏再生的影响

目的探讨门静脉动脉化重建肝血流后对肝脏再生的影响。方法建立门静脉动脉化重建肝脏血流加半肝切除(43%)的大鼠实验模型,分别在术后3 d和10 d取出肝脏烘干称重、光镜下计数进入有丝分裂期的肝细胞和分离肝细胞进行流式细胞仪分析,以观察肝脏再生的情况。结果实验组术后3 d和10 d测定的肝脏干重分别为(67.56±3.70)%(、78.76±5.68)%,与对照组(71.66±3.24)%(、82.38±4.86)%相比无显著性差异(P>0.05);进入有丝分裂期的肝细胞计数(708.4±68.21、239.6±24.50)与对照组(724.8±69.99、216.2±23.81)相比无显著性差异(P>0.05);流式细胞仪测得的进入G2和M期的肝细胞的DNA含量[(25.72±4.78)%、(15.60±2.52)%]与对照组[(28.78±3.37)%、(13.34±2.88)%]相比无显著性差异(P>0.05)。结论行门静脉动脉化重建肝血流不影响肝脏的再生。     

一种新的大鼠部分门静脉动脉化模型

目的建立操作简便、稳定可靠、重复性好的大鼠部分门静脉动脉化模型(PPVA)。方法采用""型同种异体血管材料(上、下端套袖套,侧端旷置),以套入式缝合及袖套法建立大鼠模型。切除左肾,将左肾动脉与门静脉残端、肠系膜上静脉借同种异体血管材料连接。结果 PPVA组30只大鼠中3只术后死亡,模型成功率90.0%(27/30)。术后30d,PPAV组病理检查未见异常,门静脉通畅率为96.3%(26/27),与对照组谷草转氨酶、谷丙转氨酶、血清白蛋白、胆碱酯酶、体重水平比较差异无统计学意义(P0.05)。结论采用同种异体血管借助套入式缝合及袖套法建立大鼠部分门静脉动脉化模型操作简单、重复性好、成功率高。     

门静脉动脉化对梗阻性黄疸时肝胆切除术后肝再生的影响

目的 观察慢性、梗阻性黄疸小型猪肝-胆切除术中限流性部分门静脉动脉化(PP-VA)对术后残肝再生能力的影响.方法 利用梗阻性黄疸小型猪模型,模拟进行联合半肝切除的肝门部胆管癌扩大根治性手术.实验分组:无黄疸对照组(A组)、门静脉动脉化组(B组)及非门静脉动脉化组(C组).对照观察根治术中应用限流性PPVA在术后30 d内对残肝再生的作用.结果 术后即刻及第30天门静脉PO2:B组高于C组[(47.33±2.43)比(35.38土4.06)mm Hg(1 mm Hg=0.133 kPa)、(48.50±4.44)比(35.55±2.55)mm Hg,P<0.01、P<0.01].肝细胞有丝分裂指数:术后第14及21天B组高于C组[(12.55±2.85)%比(6.85±2.10)%、(15.25±1.99)%比(11.88±1.15)%,P<0.05、P<0.05].术后第14、21天肝脏体积再生率B组分别高于C组[(24.56±6.15)%比(11.96±5.43)%、(70.63±9.83)比(44.92±7.42)%,P<0.05、P<0.01].结论 限流性PPVA可促进慢性梗黄小型猪肝-胆切除术后残肝再生,从而预防肝功能衰竭.     

Extracorporeal portal vein arterialization in man after extended hepatectomy to prevent acute liver failure: a case report

Experimental studies have shown that increasing the oxygen supply to the liver through portal vein arterialization (PVA) enhances liver regeneration after partial hepatectomy. Moreover, our previous study demonstrated a beneficial effect of an extracorporeal device to increase the oxygenated blood to the liver and to improve the survival rate of animals subjected to subtotal hepatectomy. Herein we have reported a case of PVA through an extracorporeal device to treat a man after extended hepatectomy leading to acute liver failure (ALF). An obese 69-year-old man (body mass index > 35) affected by multiple metastases from colorectal cancer underwent 80% liver resection; at laparotomy, a steatotic liver was evident due to adjuvant chemotherapy. Moreover, the liver experienced 20 minutes of hepatic ischemia during the resection. At the end of resection he underwent extracorporeal PVA treatment. Blood was withdrawn from the femoral artery and returned into the portal venous system through the umbilical vein. An extracorporeal device was interposed between the outflow and inflow to monitor hemodynamic parameters. Starting from operating room each of six treatments lasted 6 hours per day. Serum and liver samples were collected daily. The extracorporeal device was dismounted at the seventh postoperative day. The postoperative course was assessed at 1 month. The PVA-extracorporeal treatment yielded beneficial effects for subtotal hepatectomy by decreasing serum ammonia, transaminases, and total bilirubin concentration. The international normalized ratio recovered rapidly, remaining significantly lower during the entire postoperative period. The ten-day postoperative period was uneventful. The patient was discharged in good health. He is alive and well at the moment. The arterial blood supply in the portal system through the umbilical vein using an extracorporeal device was easily applicable, efficacious, safe, and cost-effective. It may represent a novel approach to treat patients with potential ALF after subtotal liver resection.     

血晶素对大鼠70%肝脏切除后再生的影响

目的 探讨血晶素(Hemin)对大鼠70%肝脏切除术后肝脏再生的影响.方法 复制大鼠70%肝脏切除模型,随机分成血晶素治疗组和生理盐水对照组,在术后第1天、第2天、第3天和第7天测定比较肝重/体重、血清肿瘤坏死因子α(TNF-α)、肝脏组织中血晶素加氧酶1(HO-1)含量及肝细胞核增殖蛋白抗原(PCNA)表达指数.结果 术后第7天治疗组肝重/体重明显高于对照组(P<0.05),第3天开始肝细胞 PCNA表达指数较对照组升高,差异有统计学意义(P<0.01).治疗组术后肝脏组织中HO-1浓度比对照组高,血清TNF-α的含量比对照组低(P<0.05).结论 血晶素大鼠肝脏70%切除术后肝脏再生的速度明显提高,这可能跟HO-1表达升高有关.     

Partial portal vein arterialization in acute liver failure

Experimental studies have shown that increasing the oxygen supply to the liver through partial portal vein arterialization (PPVA) enhances liver regeneration after extensive liver resection or drug intoxication. In the last two decades, several PPVA procedures were performed in humans with the aim to prevent or treat acute liver failure (ALF) following major hepatobiliary surgery or other etiology. The aim of this review was to analyze literature data on PPVA and report our experimental and clinical experience of this procedure. In this setting, we report our positive experience in the realization and clinical application of an extracorporeal device able to increase the oxygenated blood delivered to the liver through the umbilical vein and to support liver function in a man subjected to an extended liver resection. PPVA procedure has shown promising results in the treatment of ALF following major hepatobiliary surgery or from other etiology. Moreover, less invasive approaches to PPVA demonstrated to be safe and efficacy. It is clear that further investigations must be done to fully understand the potentiality of PPVA as a strategy to treat ALF.     

Auxiliary rat liver transplantation with portal vein arterialization in acute hepatic failure

BACKGROUND: The aim of our work was to study the effect of the portal vein arterialization of an auxiliary liver graft on survival, liver function, and regeneration of the native liver suffering from surgically induced acute liver failure (ALF). METHODS: In Lewis rats (control group: n=10), ALF was induced by resection of about 85% of liver tissue. The auxiliary liver graft (reduced size of 30%) was transplanted into the right upper quadrant of the abdomen (trial group: n=12). The portal vein was arterialized via the renal artery. The infrahepatic vena cava was anastomosed end-to-side, and the bile duct was implanted into the duodenum. RESULTS: Survival rate over a 3-month period was 10/12 in the trial group vs. 2/10 in the controls. In the trial group, the prothrombin time rose up to 38+/-2 sec on day 1 after surgery (control group: 66+/-6 sec); on day 5 after surgery, it returned to values of 30+/-1 sec. On day 1 after surgery, serum albumin fell to 25+/-1 g/L (preoperative value: 32+/-1 g/L). Within 3 weeks, it returned to normal. The hepatobiliary scan on day 7 after surgery showed normal uptake in the liver graft, whereas the uptake of the native liver was distinctly reduced. After 3 months, the transplanted liver had atrophied (0.6% of body weight), the native liver hypertrophied (2.5% of body weight), with a normal total weight for both livers of 3.1% of body weight. CONCLUSIONS: Thus, auxiliary liver transplantation with arterialized portal vein allows maintenance of liver function at the time of ALF and regeneration of the native liver.     

Clinical application of arterialization of portal vein in living related donor partial liver transplantation

Arterialization of the portal vein was employed during hepatic arterial reconstruction in our first few clinical experiences of partial liver transplantation using liver grafts obtained from living related donors. This procedure reduced the time required for revascularization of the grafts to about 25 min, and could in fact reduce the ischemic phase of the grafts. Repeated practice of the clinical transplantation technique has shortened the time needed to complete vascular reconstruction, eliminating the need for this procedure in most of our subsequent cases. In many clinical cases, however, there may be emergency situations which require vascular reconstruction, resulting in a prolongation of ischemic phase and the deterioration of the cellular viability of the graft. In such situations, arterialization of the portal vein can be a useful way to prevent the prolongation of the ischemic phase and to rescue the graft.