A model to study total hepatic ischemia-reperfusion injury

BACKGROUND: Most experimental animal models for studying hepatic ischemia-reperfusion injury (IRI) involve partial or segmental ischemia of the liver or a portocaval shunt procedure to avoid mesenteric congestion. However, these do not reflect the global ischemia that occurs during liver transplantation. A rabbit model of total hepatic ischemia without a portocaval shunt is described. METHODS: Twenty male New Zealand white rabbits (3.5 +/- 0.3 kg) were allocated to four groups: group 1 (n = 5), sham-operated; group 2 (n = 5), 20-minute total hepatic ischemia; group 3 (n = 5), 25-minute total hepatic ischemia; and group 4 (n = 5), 30-minute total hepatic ischemia. Total hepatic ischemia was induced by occluding the portal inflow vessels (portal vein and artery) with an atraumatic vascular loop and were measurements taken for 2 hours during reperfusion. RESULTS: A total hepatic ischemia of 30 minutes caused severe liver injury resulting in cardiac arrest at 2 hours of reperfusion in all five animals due to metabolic acidosis. Twenty minutes of total ischemia was tolerated and did not produce significant liver injury. Twenty-five minutes of total ischemia was tolerated but at 2 hours of reperfusion, resulted in significant liver injury (68 +/- 41, 283.0 +/- 20.5, and 835.2 +/- 52.7 U/L) compared with the sham-operated group (serum ALT, 25.4 +/- 2.7; serum AST, 47.4 +/- 3.0; serum LDH, 307.6 +/- 44.4 U/L; P < .003). CONCLUSIONS: Rabbits can tolerate 25 minutes of total hepatic ischemia without a portosystemic shunt. This 25-minute ischemia model simulates operative conditions during liver transplantation and will be valuable in studies modulating IRI.     

肝缺血再灌注对肝硬化大鼠的损伤作用

目的 研究肝硬化大鼠肝缺血再灌注（hepatic ischemia reperfusion,HIR）损伤的机制和程度。方法 用60％四经碳（CCl4）溶液皮下注射方法制作肝硬化大鼠模型，肝硬化大鼠随机分为六组：A组：假手术组（6只）；B、C、D组：分别为肝门完全阻断20min、30min、40min（每组各16只）；E组“单纯肠系膜上静脉阻断（16只）;F组：肝门阻断＋门腔转流（16只）；另外，随机取10只正常肝脏大鼠组成G组，行肝门完全阻断30min。观察7天存活率、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、透明质酸（HA）、肿瘤坏死因子（TNF），以及肝、肺病理的变化。结果 B、C、D、E、F、G组的7天存活率分别为10／10只、6／10只、4／10只、5／10只、8／10只、6／10只；再灌注后4h血清TNF变化：后六组均明显高于术前，C、D组高于B、A组，E、F组也明显高于A组（P＜0.01）再灌注4h后HA变化：D组明显高于B、E组，F、C组明显高于A组（P＜0.05）；再灌注4h后D、C组的AST、ALT均明显高于B组、A组、D组的AST明显高于F组，F组的AST、ALT显著高于E组（P＜0.05）；C、G两组比较，上述指标的差异无显著性（P＞0.05）；肝、肺组织学检查可见肝、肺的病理损害，程度随缺血时间的延长而加重，E组损伤重于F组。结论 硬化肝脏肝缺血再灌注损伤涉及全身多个器官，门脉静淤血可能是损伤乃至死亡的主要原因；肝硬化大鼠耐受肝缺血的最大的时限在30min以内。     

Extrahepatic portal vein ligation in major hepatectomies performed under selective vascular exclusion: a case-control study

The aim of our study is to assess the effect of extrahepatic ipsilateral portal vein branch ligation in hepatectomies conducted under selective hepatic vascular exclusion with sharp transection of the liver parenchyma. Twenty-six patients (Group A) underwent major hepatectomy from January 2007 to December 2009, and hemostasis was achieved by ligation of the ipsilateral portal vein branch in addition to suture ligation of the cut surface vessels. A control group (Group B) was composed of 26 matched patients picked from our hospital's database, in which hemostasis was achieved by suture ligation of the cut surface vessels only. Warm ischemia time, intraoperative blood loss, blood transfusions, and liver function were compared. Reduced blood loss (450 vs 680 mL, P = 0.03), less transfusions (8 vs 20% of the patients, P = 0.04), and decreased warm ischemia time (34 vs 42 minutes, P = 0.04) were observed in Group A. Extrahepatic ligation of the ipsilateral portal vein branch is simple, safe, and effective in reducing blood loss and warm ischemia time in major hepatectomies performed under selective vascular exclusion.     

去除门静脉淤血减轻肝脏缺血再灌注损伤的实验研究

目的 探讨去除门静脉淤血对肝脏缺血再灌注损伤的影响及机制.方法 检测家兔肝脏原位冷灌注20、30、40 min后淤血的门静脉中内毒素含量变化,观察门静脉淤血去除对恢复灌流后4 h血清内毒素、丙氨酸转氨酶(ALT)、透明质酸(HA)、肝组织匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)及肝组织核因子-κB(NF-κB)活性的影响.结果 门静脉淤血中内毒素含量随阻断时间延长明显升高(P＜0.01),同一阻断时间每去除2.5 ml淤血血清内毒素含量显著下降(P＜0.01).在阻断30 min和40 min组,去除门静脉淤血能降低血清ALT、HA、及肝组织匀浆MDA的含量和肝组织NF-κB活性,增加肝组织匀浆SOD活性,与不去除相比较差异有统计学意义(P＜0.05).在阻断20 min组去除门静脉淤血与不去除相比较,各检测指标差异无统计学意义(P＞0.05).结论 门静脉淤血中内毒素含量随阻断时间延长明显升高,可能是引起肝脏损伤的主要原因;去除门静脉淤血可以减轻肝脏的再灌注损伤,其机制可能与门静脉淤血去除减少内毒素吸收,进而降低肝组织NF-κB活化有关.     

The effect of nifedipine, a calcium channel blocker, on liver ischemia in dogs

This study was undertaken in order to determine whether the administration of nifedipine, a calcium channel blocker, could protect the liver from ischemic damage and to investigate its effect on the hepatic cellular energy status and cardio-vascular system after 60 minutes of hepatic ischemia in dogs. The ischemia was induced by temporarily clamping the portal vein and hepatic artery. One group of animals (n = 17) received nifedipine (5 micrograms/kg body weight) intravenously 15 minutes before the induction of liver ischemia, which was continued at a dose of 0.2 microgram/kg body weight/min throughout the ischemic period, and for an additional 30 minutes afterwards. Control dogs (n = 16) were not given nifedipine and survival was observed over seven days. The survival rate was 83 per cent in the nifedipine treated animals and 0 per cent in the control animals. Serum glutamic oxaloacetic transaminase levels were greatly increased following ischemia, and they were significantly lowered with the nifedipine treatment. The hepatic energy charge decreased remarkably during the hepatic ischemia, however it increased gradually after declamping but did not returned to its preoperative value in either group until one hour later and then it was higher in the nifedipine treated animals than in the control animals. Cardiac index and portal venous blood flow ratio remained higher in the nifedipine treated animals than in the control animals, after the ischemic period. These results suggest that nifedipine may have a powerful cytoprotective effect and that the period of warm hepatic ischemia could be prolonged with its use.     

梗阻性黄疸SD大鼠肝热缺血再灌注损伤模型的建立

目的构建阻塞性黄疸合并肝热缺血再灌注损伤的SD大鼠模型。 方法选择SD大鼠40只随机分为4组：假手术组（Sham组）、梗阻7天组（7 d组）、梗阻14天组（14 d组）及梗阻21天组（21 d组）,每组10只。通过双重结扎并切断胆总管建立SD大鼠阻塞性黄疸模型,探索最佳梗阻时间。梗阻7 d后另择SD大鼠62只,再随机分为4组：未缺血组（0 min组,10只）、缺血15 min组（15 min组,12只）、缺血30 min组（30 min组,16只）、缺血45 min组（45 min组,24只）,分别行肝门部血管阻断0、15、30、45 min后再灌注,建立后续肝热缺血再灌注损伤模型,观察生化指标、生存率及病理学改变。 结果梗阻7 d时适合下一步建模。建立阻塞性黄疸模型后,随着肝门部血管阻断时间的延长,肝功能进行性下降,大鼠死亡率逐渐升高,各组间的差异具有统计学意义（P<0.05）;随阻断时间的延长,肝脏损害的病理学表现更为严重。其中肝门部血管阻断30 min时24 h死亡率50%,再灌注2 h后病理学上出现严重的肝细胞变性、坏死改变。 结论对于梗阻性黄疸的SD大鼠,在梗阻7 d后行肝门部血管阻断30 min再恢复血流,可有效建立梗阻性黄疸大鼠的肝缺血再灌注损伤模型。     

The effect of nifedipine,a calcium channel blocker,on liver ischemia in dogs

This study was undertaken in order to determine whether the administration of nifedipine, a calcium channel blocker, could protect the liver from ischemic damage and to investigate its effect on the hepatic cellular energy status and cardio-vascular system after 60 minutes of hepatic ischemia in dogs. The ischemia was induced by temporarily clamping the portal vein and hepatic artery. One group of animals (n=17) received nifedipine (5 μg/kg body weight) intravenously 15 minutes before the induction of liver ischemia, which was continued at a dose of 0.2 μg/kg body weight/min throughout the ischemic period, and for an additional 30 minutes afterwards. Control dogs (n=16) were not given nifedipine and survival was observed over seven days. The survival rate was 83 per cent in the nifedipine treated animals and 0 per cent in the control animals. Serum glutamic oxaloacetic transaminase levels were greatly increased following ischemia, and they were significantly lowered with the nifedipine treatment. The hepatic energy charge decreased remarkably during the hepatic ischemia, however it increased gradually after declamping but did not returned to its preoperative value in either group until one hour later and then it was higher in the nifedipine treated animals than in the control animals. Cardiac index and portal venous blood flow ratio remained higher in the nifedipine treated animals than in the control animals, after the ischemic period. These results suggest that nifedipine may have a powerful cytoprotective effect and that the period of warm hepatic ischemia could be prolonged with its use.     

入肝血流阻断对局部热消融治疗肝癌疗效影响的研究

目的　研究入肝血流阻断对局部热消融治疗肝癌效果的影响 ,为临床提高局部热消融治疗肝癌疗效提供实验依据。方法　利用SD大鼠 ,采用癌组织块包埋法建立大鼠W 2 5 6肝癌模型 4 0只。随机分 4组 ,每组 10只 :肝门非阻断组 (A组 ) ;肝动脉阻断组 (B组 ) ;门静脉阻断组 (C组 ) ;肝动脉和门静脉联合阻断组 (D组 )。对 4 0只大鼠的癌灶 ,应用自我研制的半导体锥形散射激光热疗系统进行辐照。比较辐照时的癌灶温度 ,并观察辐照后即刻、1周、2周的组织学变化。结果　 4组间各时点癌灶温度比较差异有显著性 (P <0 0 1) ;4组间各时点癌灶温度两两比较 ,除B组和C组在 12 0秒时点和C组、D组各时点差异无显著性 (P >0 0 5 )外 ,其余组间各时点癌灶温度两两比较差异均有显著性 (P <0 0 5 )。光学显微镜下见 4组SD鼠癌灶标本以治疗头为中心 ,向外依次为凝固坏死区、移行区和正常肝癌细胞对照区。C、D组比A、B组三区分界清楚。结论　入肝血流阻断可提高激光热消融治疗肝癌的疗效 ,以联合阻断或门静脉阻断效果最好 ,肝动脉阻断次之。     

保留半肝动脉血供肝血流安全阻断时限的研究

目的：探讨门静脉自然转流及非转流情况下保留半肝动脉血供肝血流阻断的安全时限。方法：将实验大鼠分为A、B、C组。A组保留肝左、肝中动脉血供及尾状叶动脉、门静脉血供（约占全肝5％）,夹闭肝左、肝中0tl＇]静脉,结扎肝右叶肝蒂,到预定阻断时相点,恢复肝脏灌流,切除肝右叶及尾状叶,24h后检测ALT、肝脏HE染色（细胞核）BSJI~面积的平均百分数及术后7d存活率。B组不保留尾状叶动脉、门静脉血供,其他与A组相同。C组完全阻断肝脏入肝血流,肝切除方式及检测指标与A组相同。结果：在A、B、C3组中,A组的阻断形式对肝脏的损害最轻,B组次之,C组最重。A/100、B／40与C／20损害程度相当。结论：大鼠门静脉转流下保留半肝动脉血供入肝曲流阻断的安全时限是100min,单纯保留半肝动脉血供入肝血流阻断组的安全时限是40min。     

The effect of intraportal prostaglandin E1 on adhesion molecule expression, inflammatory modulator function, and histology in canine hepatic ischemia/reperfusion injury

BACKGROUND: Prostaglandin E1 (PGE1) is known to protect the liver from I/R, however, the mechanism of cytoprotection is not well understood. This study investigates the effect of intraportal infusion of PGE1 in a warm liver ischemia/reperfusion (I/R) model on cytokines, adhesion molecules and liver structure. MATERIALS AND METHODS: Twenty dogs underwent laparotomy under general anesthesia. PGE1 (0.02 microg\kg\min) was perfused through the portal vein in the PGE1 group (n = 10), or a similar volume of Ringer's solution in the control group (n = 10) for 15 min. Liver ischemia was induced by hepatic artery and portal vein occlusion and PGE1 was infused via the portal vein for 60 min. The occlusion was released and PGE1 infusion recommenced for 30 min. Blood and liver biopsies were sampled at baseline, 60 min ischemia, and 30 min reperfusion and assessed for transaminases, cytokines, adhesion molecules, and electron microscopy. RESULTS: PGE1 infusion significantly reduced transaminases TNF-alpha, sICAM-1, sP-selectin, and sE-selectin on ischemia and reperfusion. PGE1 reduced hepatocytic degeneration, portal and central ICAM-1 expression, central and sinusoidal VCAM-1 expression, portal and central P-selectin expression, and portal and sinusoidal E-selectin expression on reperfusion. CONCLUSION: Intraportal PGE1 infusion reduced I/R injury and was associated with down-regulation of ICAM-1, VCAM-1, P-selectin, and E-selectin on reperfusion.     

加氧低温灌流下31磷-磁共振频谱与肝酶测定在判断大鼠供肝活力中的意义

目的　探讨判断经受热缺血的肝脏活力的方法。方法　将 18只SD大鼠随机分成 3组 :A组肝脏热缺血时间 (WI)为 0min ;B组WI为 30min ;C组WI为 6 0min。各组肝脏冷保存后 2～2 .5h ,采用31磷 磁共振频谱 (31P MRS)测定各组加氧低温灌流 30min时的离体肝脏频谱 ,同时测定保存液和灌流液中肝酶的变化。结果　β 三磷酸核酸 (β NTP)与亚甲基二磷酸 (MDP)的比值 ,B组与A组比较 ,P >0 .0 5 ;C组与A、B组比较 ,P <0 .0 1。肝酶测定结果 :随着热缺血时间的延长 ,保存液中的肝酶逐渐升高 ,每组之间比较 ,差异均有显著性 (P <0 .0 5 ) ;灌流液中的肝酶 ,A组与B组比较 ,差异无显著性 (P >0 .0 5 ) ,C组与A、B两组比较 ,差异均有极显著性 (P <0 .0 1)。结论　测定加氧低温灌流下大鼠离体肝脏的ATP再生能力能较好判断其活力 ,该方法在临床热缺血供肝活力的判断上具有一定参考价值 ;同时测定保存液和灌流液中的肝酶含量 ,能配合31P MRS判断肝脏的活力。     

Experimental evaluation of the effects of the intraportal administration of cyclic guanosine monophosphate on ischemia/reperfusion in the porcine liver

This study was done to examine the protective effects of cyclic guanosine monophosphate (cGMP), a second messenger of nitric oxide, for ischemia/reperfusion injury of the liver, since it is known to induce vasodilatation and to inhibit platelet aggregation. Using an experimental model of porcine liver ischemia, 8-bromoguanosine 3′,5′ monophosphate, a cGMP analog, was continuously administered into the portal vein before ischemia and after reperfusion 30 min for each in the cGMP group (n=6). Saline water was administered in the same way in the control group (n=6). The cardiac output (CO), mean arterial blood pressure (MAP), portal venous flow (PVF), hepatic arterial flow (HAF), hepatic tissue blood flow (HTBF), and hepatic tissue cGMP level were determined. Hepatic enzymes and the bile discharge were also assessed as indicators of hepatic function. The hepatic tissue cGMP level was significantly higher, and PVF, HTBF, and the bile discharge were significantly greater in the cGMP group, while there were no remarkable differences between the groups with CO, MAP, HAF, and hepatic enzymes. In conclusion, the continuous supplementation of cGMP into the portal vein was found to be beneficial for preserving both the hepatic circulation and, consequently, the hepatic function of after warm ischemia of porcine liver.     

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     

门静脉转流下大鼠门静脉缺血对肝脏能量代谢的影响

目的探讨在门静脉转流下大鼠门静脉缺血后肝脏能量代谢变化。方法在门静脉转流下阻断门静脉不同时间后,观察大鼠存活率、肝细胞线粒体呼吸活性、肝组织ATP含量及动脉血酮比值。结果在门静脉缺血60、90及120min后7d大鼠存活率分别为100%、100%及40%;缺血后肝脏能量代谢功能明显受损,再灌注后24h,门静脉缺血60、90min两组大鼠肝脏能量代谢功能已有明显恢复,而门静脉缺血120min组仍维持在低水平。结论在门静脉转流下大鼠门静脉缺血90min以内肝脏能量代谢损害可逆,而门静脉缺血120min则不可逆。     

A free radical scavenger, edaravone, prevents ischemia-reperfusion injury in liver grafts from non-heart-beating donors

BACKGROUND: Due to the increase in liver transplantation, the donor shortage has become a serious problem, requiring marginal, non-heart-beating donors (NHBDs). The aims of this study were to evaluate the cytoprotective effect of edaravone, a free radical scavenger, on warm ischemia-reperfusion (I/R) injury of liver grafts from NHBDs. METHODS: Rat livers were harvested from heart-beating donors (HB group) or from NHBDs undergoing cardiac arrest for 30 minutes led by thoracotomy (NHB group), and reperfused for 60 minutes with Krebs-Henseleit bicarbonate buffer after cold preservation for 6 hours. In another group (ED group), warm ischemic livers from NHBDs were reperfused with buffer containing edaravone (1 mg/L) after cold preservation. RESULTS: In the ED group, portal flow volume, bile production, and energy charge were significantly ameliorated. Lipid peroxidation, elevation of hepatic enzymes, and release of tumor necrosis factor-alpha and interleukin-1 beta were significantly alleviated, compared with the NHB group. CONCLUSIONS: These results suggested that edaravone has suppressive effects on warm I/R injury in liver grafts from NHBDs.     

Synthetic sulfonolipids deduced from sulfonoquinovosyl diacylglycerols of sea urchin reduces hepatic ischemia-reperfusion injury in rats

BACKGROUND: In hepatic surgery and liver transplantation, ischemia-reperfusion (I/R) is an unavoidable process, and protection against hepatic I/R injury is a major unresolved problem. In this study, we investigated whether 3-O-(6-deoxy-6-sulfono-beta-D-glucopyranosyl)-1,2-di-O-acylglycerol bound to saturated C18 fatty acids (beta-SQAG9), which was derived from sea urchin intestines, could reduce this injury. This agent was recently reported to have immunosuppressive effects in allogeneic rat skin grafts. MATERIALS & METHODS: Male Lewis rats were divided into two experimental groups. Group 1 rats were injected with SQAG9 (50 mg/kg) into the penile vein 15 minutes before the induction of ischemia and into the portal vein just reperfusion. The same amounts of normal saline were injected into rats in the control group (group 2). Each experimental groups included six rats. Seventy percent hepatic ischemia (20 minutes) was induced by occluding the blood vessels and bile duct with a vascular clamp. For examination of hepatic function, serum levels of aspartate aminotransferase, (AST) alanine transaminase (ALT), and lactic dehydrogenase (LDH) were measured. In addition, histological examination was also assessed. RESULTS: Three hours after reperfusion, the mean plasma concentration of AST, ALT, LDH in group 1 was suppressed compared with group 2. Six hours after reperfusion, the hepatic damage in group 1 was mild in comparison with that in group 2. CONCLUSIONS: Our data demonstrated that SQAG-9 reduced the warm hepatic I/R injury.     

Hemodynamic profiles during piggyback liver grafts using arterial or portal revascularization

BACKGROUND: The order of revascularization in human liver grafts is still discussed. This study tries to answer this question in terms of hemodynamic data. STUDY DESIGN: Fifty-nine patients were randomized in this study to compare hemodynamic data just before and 15 minutes after revascularization of liver grafts in relation to first hepatic artery (n = 29) or first portal vein (n = 30) revascularization procedure. RESULTS: Hemodynamic variations were significantly greater in the portal vein group than in the hepatic artery group in terms of mean arterial pressure, cardiac index, central venous pressure, pulmonary capillary pressure, and systemic vascular resistance. The latter decreased from 741.8 +/- 390.3 to 659.9 +/- 411.1 dynes/ cm5 (NS) in the hepatic artery group versus 807.7 +/-336.7 to 439.7 +/- 215 dynes/cm5 (p < 0.05) in the portal vein group. Clinical results and postoperative complications, graft characteristics, patient survival, and graft survival were not significantly different between the groups. CONCLUSIONS: Initial arterial revascularization of the liver graft leads to a more stable hemodynamic profile during revascularization of the liver graft after vascular unclamping. This technique is always feasible and has become our reference procedure.     

Portal vein pressure and graft oxygen consumption monitoring during liver transplantation

Abnormal splanchnic circulation (ASC) is often detected too late, when hepatic circulation is already irreversibly compromised. If we could detect surgical or metabolic problems early after graft reperfusion, we might be able to correct them immediately before the damage becomes irreversible. The aim of this study was to determine if ASC can be predicted early after liver transplantation (LT) using portal vein pressure measurements and graft oxygen consumption monitoring. PATIENTS AND METHODS: Twenty-patients (13 men, 7 women of mean age 46 years) undergoing LT with the piggyback technique for hepatitis C virus (HCV)/hepatitis B virus (HBV)-related cirrhosis were retrospectively divided in two groups. Group A (16 patients), in which LT was successful, and group B (4 patients) in which LT was unsuccessful because of primary nonfunction (2 patients), infrahepatic portal vein thrombosis (1 patient), or hepatic vein kinking (1 patient). We then compared the portal blood pressure values and the prehepatic and posthepatic oxygen content difference (p-pDO(2)) before portal clamping; at the end of anhepatic phase; 5, 15, and 25 minutes after portal vein (PV) reperfusion; and 5, 20, 40, and 100 minutes after hepatic artery anastomosis. RESULTS: Early after graft reperfusion; portal pressure decreased to levels lower than that at baseline in group A, but remained high until the end of surgery in group B. At the end of surgery, p-pDO(2) increased more among group B than group A. CONCLUSION: ASC, specifically an increased PV resistance, can be predicted early after LT by portal vein pressure measurements and graft oxygen consumption monitoring.     

Novel nitric oxide donor (FK409) ameliorates liver damage during extended liver resection with warm ischemia in dogs

BACKGROUND: Nitric oxide attenuates ischemia-reperfusion injury by maintaining organ circulation through its actions as a vasoregulator, an inhibitor of platelet aggregation, and an attenuator of leukocyte adhesion. Otherwise, the harmful effects of enhanced nitric oxide production induced by inducible nitric oxide synthase mediate ischemia-reperfusion injury. FK409 has been characterized as a spontaneous nitric oxide donor. The aim of this study was to evaluate the effects of FK409 on extended liver resection with ischemia using a canine model. STUDY DESIGN: Adult mongrel dogs were subjected to 60 minutes of warm ischemia by partial inflow occlusion. After reperfusion the nonischemic lobes were resected and the remnant liver function was evaluated. The dogs were divided into two groups: the control group (n = 7) and the FK409 group (n = 6), which was given FK409 through the portal vein. RESULTS: The hepatic tissue blood flow, serum liver enzymes levels, and serum endothelin-1 level after reperfusion were significantly better in the FK409 group than in the control group. Electron microscopy demonstrated that endothelial cells and Ito cells were well-preserved in the FK409 group. The 3-day survival rate was statistically better in the FK409 group (67%) than in the control group (14%). CONCLUSIONS: FK409 appears to have protective effects during extended liver resection with ischemia.     

供体热缺血时间对移植肝的影响

目的 探讨大鼠动脉化原位肝移植中供体热缺血时间对移植肝的影响.方法 实验分为4组:对照组(C)和移植组,移植组根据供肝获取前经历供体心脏停搏时间的不同分为三组:热缺血0 min(W0)、热缺血15 min(W15)和热缺血30 min(W30),其后建立近交系大鼠动脉化原位肝移植模型,每组均为30只大鼠,分别于术后3、7、14和30 d处死,每个时间点各取6只大鼠,分别测定移植肝组织学、肝功能的变化.此外,移植组各组随机选取6只大鼠观察长期生存率(＞100 d).结果 随着供肝热缺血时间的延长,移植肝损伤加重,恢复过程延长.移植组和对照组术后3、7、14和30 d血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)变化无显著性差异.血清碱性磷酸酶(ALP)随着供肝热缺血时间的延长逐渐增高,14 d达到高峰后逐渐下降.术后3、7、14和30 d ALP与供肝热缺血时间具有显著相关性.术后热缺血0、15、30 min长期生存率组分别为100.0%(6/6)、83.3%(5/6)、66.7%(4/6),3组间比较差异无统计学意义(P=0.285).结论 肝移植过程中供肝热缺血主要损伤肝细胞,并随着供肝热缺血时间的延长移植肝细胞损伤加重,肝细胞功能恢复早于其形态学恢复.肝移植术后早期存在胆汁淤积,供肝热缺血时间的延长明显加重胆汁淤积的程度,胆汁淤积的恢复明显晚于肝细胞损伤指标的恢复.在热缺血30 min内来自于心脏停搏的供肝肝移植术后是安全的.