Improved microcirculation of a liver graft by controlled portal vein arterialization

BACKGROUND: The clinical results of portal vein arterialization (PVA) in liver transplantation are controversial without a standardized portal flow regulation. The aim of these experiments was to perform a flow-regulated PVA in liver transplantation, to examine the microcirculation and early graft function after heterotopic auxiliary liver transplantation (HALT) with flow-regulated PVA, and to compare this technique with HALT with porto-portal anastomosis. Using the recently developed orthogonal polarization spectral (OPS) imaging, for the first time the microcirculation of liver grafts with PVA was visualized. MATERIALS AND METHODS: HALT was performed in Lewis rats. The portal vein was either completely arterialized via the right renal artery in a standardized splint-technique (Group I, n = 8) or anastomosed end-to-end to the recipient's portal vein (Group II, n = 8). RESULTS: After reperfusion, the average blood flow in the portal vein was within the normal range in Group I (1.7 +/- 0.4 ml/min/g liver weight) and significantly higher than in Group II (1.2 +/- 0.2 ml/min/g liver weight). The functional sinusoidal density in Group I (335 +/- 48/microm) was significantly higher than in Group II (232 +/- 58/microm), whereas the diameter of the sinusoids and the postsinusoidal venules yielded no significant differences between both groups. The bile production was comparable (27 +/- 8 versus 29 +/- 11 microl/h/g liver weight). CONCLUSIONS: In our experiments it was possible to achieve an adequate flow regulation in the arterialized portal vein with good results concerning microcirculation and early graft function. We recommend that further investigations on liver transplantation with PVA should be performed with portal flow regulation, before PVA is employed in clinical transplantation.     

A rare case of complex vascular reconstruction in liver transplantation.

Abnormalities of recipient or donor vascular structures are associated with reconstructive difficulties in liver transplantation. A patient with thrombosis of the right hepatic vein and associated stricture of the inferior vena cava (IVC), portal vein thrombosis and multiple aberrant arteries underwent orthotopic liver transplantation. The donor's suprahepatic IVC was anastomosed to the recipient's intrathoracic IVC. The portal vein flow was restored by venous graft interposition, while the arterial flow was ensured by interposing an iliac arterial graft anastomosed to the infrarenal aorta. In conclusion, graft function remains excellent more than 5 years postoperatively.     

Competition between native liver and graft in auxiliary liver transplantation in a rat model

The competition between the native and the grafted liver in heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) was investigated in a rat model. The experimental groups were: HALT with flow-regulated PVA and 70% resection of a native liver and graft (n = 32; group I) versus 70% liver resection (n = 32; group II). After HALT, the weight of the native liver increased until the sixth postoperative week (431% +/- 55% of the intraoperative weight), whereas, the graft weight was only 76% +/- 31% of the intraoperative weight at this time. In group II, liver weight increased continuously to 529% +/- 30% of the intraoperative weight after 6 weeks. On postoperative day 2, there was significantly increased proliferative hepatocellular activity in all groups. This was highest in the resected livers of group II, followed by the native livers of group I, and the grafts of group I (301 +/- 126 vs 262 +/- 97 vs 216 +/- 31 Ki-67-positive hepatocytes/10 visual fields). However, the differences between the groups were not significant. With regard to hepatocellular apoptosis, the livers were similar among all groups and at all time points, M30-positive hepatocyte counts were 相似文献   

Auxiliary liver-heart transplantation in the rat: a new microsurgical model inducing tolerance

OBJECTIVE: To establish a model of immunological tolerance induced by simultaneous auxiliary liver transplantation and heterotopic heart transplantations using PVG and DA rats as donors and recipients respectively, to provide a new method for the research of liver transplantation. METHODS: The recipient's whole portal vein blood was transfered to the auxiliary liver allograft. The donor's heart was transplanted to the recipient's abdominal cavity by end-to-side anastomosis of the donor aorta and pulmonary artery to the recipient aorta and vena cava, respectively. RESULTS: In the syngeneic control group and the test group the recipient rats and their transplanted hearts both survived more than 100 days, while the hearts of alloheart control group only survived 6 days. The weight of the liver graft increased slowly. CONCLUSIONS: In the presence of recipient liver, the auxiliary liver graft functioned well to induce tolerance. At 100 days, the auxiliary liver graft had increased in volume and weight with maintenance of its tolerance-inducing effects.     

Auxiliary liver transplantation in acute liver failure in the rat – an illustrated description of a new surgical approach

INTRODUCTION: To investigate auxiliary liver transplantation successfully in rats suffering from acute liver failure, we developed a new surgical approach. METHODS: A 70% hepatectomized liver graft was implanted into the right upper quadrant of the abdomen. The donor portal vein was anastomosed with the recipient's right renal artery using the splint technique. The donor infrahepatic vena cava was attached onto the recipient vena cava end to side. The bile duct was implanted into the duodenum.     

猪辅助性部分肝移植模型制作及比较

目的建立猪的辅助性部分肝移植模型,观察其肝功能和术中血流动力学变化。方法 24头健康良种家猪,体质量23-30 kg,被随机分为供体(n=12)和受体(n=12)。气管插管 全麻,硫喷妥钠静脉维持。移植前切除受体肝左叶,供肝右叶作为植入肝。预实验2例行经体位转流的原位辅助性部分肝移植,对照组(5例)行简易转流下的原位辅助性部分肝移植。模型组(5例)行异位辅助性部分肝移植, 供肝被植入受体肝下间隙,供肝肝上下腔静脉与受体肝下下腔静脉端侧吻合,供肝门静脉与受体门静脉行端侧吻合,供肝肝动脉与受体脾动脉行端端吻合。供肝胆总管置管外引流。结果预实验中行体位静脉转流的原位辅助性部分肝移植的2例受体在肝上下腔静脉阻断后很快陷入血流动力学紊乱死亡。5例行简易静脉转流的原位辅助性部分肝移植的受体,2例在24 h内死亡,1例28 h,2侧超过48 h。而模型组受体 5例中有4例存活超过24 h。AST,ALT指标手术开始至术后24 h呈持续升高。模型组术中血流动力学较其他组稳定。结论该辅助性肝移植模型简明易建且具有不需静脉转流等优点,为研究辅助性部分肝移植原肝和供肝功能及血流变化提供了理想的平台。     

Portal hyperperfusion causes disturbance of microcirculation and increased rate of hepatocellular apoptosis: investigations in heterotopic rat liver transplantation with portal vein arterialization

Clinical results of portal vein arterialization (PVA) in liver transplantation are controversial. One reason for this is the lack of a standardized flow regulation. Our experiments in rats compared PVA with blood-flow regulation to PVA with hyperperfusion in heterotopic auxiliary liver transplantation (HALT). In group I (n = 19), the graft's portal vein was completely arterialized via the right renal artery in-stent technique, using a 0.3-mm stent, leading to a physiological average portal blood flow. In group II (n = 19), a 0.5-mm stent was used. In group II, the average portal blood flow after reperfusion was significantly elevated (group II: 6.4 +/- 1.5; group I: 1.7 +/- 0.4 mL/min/g of liver weight; P < .001). The sinusoidal diameter after reperfusion was significantly greater in group II (9.8 +/- 0.5 microm) than in group I (5.5 +/- 0.2 microm; P < .001). Red blood cell velocity in the dilated sinusoids was significantly lower in group II (171 +/- 18 microm/s) than in group I (252 +/- 13 microm/s). Stasis of erythrocytes occurred; consequently, the functional sinusoidal density was significantly reduced in group II (38 +/- 7%) compared with group I (50 +/- 3%; P < .01). Two hours after reperfusion of the portal vein, the number of apoptotic hepatocytes was significantly higher in group II than in group I (I: 0 +/- 0 vs II: 7 +/- 9 M30-positive hepatocytes/10 high-power fields). The 6-week survival rate was 9 of 11 in both groups. In group II, 6 of 9 grafts showed massive hepatocellular necroses after 6 weeks, whereas in group I, only 1 of 9 presented a slight hepatocellular necrosis. Finally, our results demonstrate negative effects of portal hyperperfusion in transplanted livers, which are correctable by adequate flow regulation.     

A Novel Technique for Auxiliary Partial Liver Transplantation With Reno-Portal Anastomosis and Avoidance of the Hepatoduodenal Ligament

Auxiliary liver transplantation (ALT) is a treatment for acute liver failure when regeneration of the native liver is possible or for metabolic disorders. In selected cases ALT and orthotopic liver transplantation (OLT) have similar survival when ALT is performed in the orthotopic position (auxiliary partial orthotopic liver transplantation, APOLT). Drawback of ALT with portal vein to portal vein anastomosis is the frequent occurrence of thrombosis, compromising both graft and native liver, and the necessity of a significant resection. To avoid division of portal flow we performed ALT with an end-to-end anastomosis between the graft portal vein and the left renal vein of the recipient (reno-portal ALT, REPALT). The hepatic artery was anastomosed to the aorta using an iliac arterial graft conduit. The bile duct was anastomosed to the stomach. In the two cases presented here excellent immediate graft function occurred with rapid regeneration of the graft and without early vascular complications.     

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.     

A new method for rat accessory hepatic transplantation — the cervical approach

Current methods for accessory liver transplantation in the rat require a high degree of microsurgical expertise and long training before success is achieved. We present a simpler method of arterialized accessory liver transplantation using the cervical vessels for revascularization of the transplanted liver with the cuff technique, which is useful for studies of liver preservation, reperfusion injury, and liver regeneration. After classical 70% hepatectomy is performed on the graft, the right common carotid artery is anastomosed to the donor aorta, the distal right external jugular vein is anastomosed to the donor portal vein, and the proximal right external jugular vein is anastomosed to the donor supradiaphragmatic inferior vena cava. The skin is not closed over the cervically transplanted liver (CTL). This method was used 30 times for periods of up to 6 h with a 90% success rate. CTL structure and function, as revealed by histology, bile flow rates, biliary bilirubin concentrating capacity, membrane potential, enzyme activity and distribution, have shown the CTL to be a structurally normal and metabolically active graft. In conclusion, the cervical approach to arterialized accessory liver transplantation is simple, and should prove useful for studies of liver preservation, reperfusion, regeneration, physiology, and toxicology.     

Auxiliary liver transplantation with flow-regulated portal vein arterialization offers a successful therapeutic option in acute hepatic failure – investigations in heterotopic auxiliary rat liver transplantation

Heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) was proposed in acute hepatic failure (AHF). However, clinical results of PVA are controversial because of lacking standardized flow-regulation. In rats, we examined HALT with flow-regulated PVA in AHF. Group A: HALT with flow-regulated PVA and 85% resection of the native liver to induce AHF [acute experiments (n = 8), killing after 7 days (n = 8) and after 6 weeks (n = 11)]. Group B: 85% liver-resection (n = 10). The average blood-flow in the arterialized portal vein in HALT achieved normal values (1.7 +/- 0.4 ml/min/g liver-weight). After reperfusion, the diameters of the sinusoids (6.4 +/- 0.6 microm), the postsinusoidal venules (31.1 +/- 3.3 microm) and the intersinusoidal distance (17.9+/-0.7 microm) also achieved normal values. The functional sinusoidal density amounted to 335 +/- 48/cm. The 6-week survival was nine of 11 with excellent liver function (Quick's value: 110% +/- 7.8%). The hepatobiliary radioisotope scanning with (99mTc) ethyl hepatic iminodiacetic acid (EHIDA) showed no significant differences between the native livers and grafts. The hepatocellular morphology was regular, apart from low-grade necroses in two grafts. The grafts' sinusoidal endothelial cells did not show any morphological changes. In group B, however, all rats died from AHF within 6 days. HALT with flow-regulated PVA achieved good results regarding microcirculation, morphology and function and can reliably bridge AHF.     

大鼠辅助性肝移植诱导免疫耐受模型的建立

目的利用PVG（TR-1^c）和DA（RT-1^a）大鼠分别为供受体，联合进行辅助性肝移植和异位心脏移植，建立大鼠辅助性肝移植诱导免疫耐受模型。方法辅助性肝移植采用重建门静脉法，异位心脏移植采用腹腔吻合法。结果同品系对照组和实验组动物及其移植心脏存活超过100d，而异品系对照组移植心脏只存活7d。结论在受体肝脏存在的情况下，辅助性供肝依然发挥其诱导耐受的效应。经长期观察，供肝无萎缩，耐受诱导效应持续存在，指示心脏搏动良好。因此，该模型在肝移植基础研究中具有实用价值。     

大鼠胰腺十二指肠移植的手术技巧

目的探讨建立大鼠胰腺十二指肠移植模型的手术技巧。方法不阻断体循环，采用双套管将供胰所带腹主动脉、门静脉分别与受鼠的左肾动、静脉进行套管吻合，尽量减轻对全身血流动力学的影响；同时行十二指肠空肠端侧吻合引流胰液，重建胰腺外分泌途径；围手术期注意补液、保暖及抗凝。结果100例手术中83例手术成功，术后移植胰腺具有内分泌功能，胰腺轻度充血水肿。结论该移植模型不阻断体循环且操作简单实用，其成功的关键在于手术操作及围手术期处理。     

Auxiliary liver transplantation with arterialization of the portal vein for acute hepatic failure

Six adult patients suffering from acute hepatic failure and with a high urgent status underwent heterotopic auxiliary liver transplantation. In four of these patients, the portal vein of the liver graft was arterialized in order to leave the native liver and the liver hilum untouched and to be able to place the liver graft wherever space was available in the abdomen. The arterial blood flow via the portal vein was tapered by the width of the anastomosis. Two patients died, one of sepsis on postoperative day 17 (POD), the other after 3 months due to a severe CMV pneumonia. There were no technically related deaths. The native liver showed early regeneration in all cases. In one patient, the auxiliary graft was removed 6 weeks after transplantation. Four weeks later, he had to undergo orthotopic retransplantation due to a recurrent fulminant failure of the recovered native liver. This patient is alive more than 1 year after the operation. We conclude that heterotopic auxiliary liver transplantation with portal vein arterialization is a suitable approach to bridging the recovery of the acute failing native liver. Received: 15 September 1997 Received after revision: 4 February 1998 Accepted: 2 March 1998     

20%小体积的大鼠肝脏移植模型

目的 应用显微外科技术建立20%小体积移植物的大鼠原位肝脏移植模型.方法 原位移植建立20%小体积大鼠肝脏移植模型.雄性Lewis大鼠40只,供体20只,受体20只.供肝经门静脉用4℃ UW液灌注.肝上下腔静脉用端端吻合连续缝合的方法.肝下下腔静脉和门静脉分别用套管方法固定.套叠缝合法重建肝动脉.胆管重建采用内支架管端端连接的方法.观察移植物的存活率.免疫组化检测肝细胞摄取溴脱氧尿核苷的情况.结果 共施行肝脏移植手术20例,移植手术成功率为100%.20%小体积肝脏移植物的存活率为93.8%(＞14 d).组织学检查移植后的肝脏组织结构良好.移植术后72 h溴脱氧尿核苷染色阳性的肝细胞计数明显增多.结论 20%小体积大鼠肝脏移植物可启动完成移植后的肝脏再生.显微外科技术是移植模型成功的关键.该模型稳定性强,适合于部分肝脏移植领域的基础研究.     

Arterialization of the portal vein in liver transplantation: a new microsurgical model in the rat

BACKGROUND: A preexisting thrombosis of the portal vein and the deep splanchnic bed can make it extremely difficult to reestablish the portal blood flow in orthotopic liver transplantation in man. Complete arterialization of the liver transplant, including the donor portal vein, might be a viable therapeutic option. A new rat transplantation model is described, in which the liver is completely arterialized. METHODS: The outflow of the portal blood in the recipient was secured via a portocaval shunt. Hepatectomy was then performed and the liver transplant placed in orthotopic position. An interposed aortic segment was used for direct arterialization of the donor portal vein. RESULTS: The laboratory parameters determined in the serum at the end of the observation period of 28 days revealed normal functioning of the transplant. The histological examinations showed largely normal cellular architecture, with no signs of necrosis, but incipient fibrosis. CONCLUSIONS: Using this new surgical technique in the rat liver transplantation model, long-term morphological and functional changes in a completely arterialized liver graft, and the regenerative capability of liver tissue perfused in this way, can be investigated.     

成人间活体扩大右半肝移植治疗急性肝功能衰竭

目的介绍成人间活体扩大右半肝移植治疗急性肝功能衰竭的临床经验。方法对1例42岁男性急性肝功能衰竭合并肝性脑病Ⅲ期患者行活体扩大右半肝移植治疗。其45岁姐姐为供者,CT评估供者包含肝中静脉的扩大右半肝体积为728．4cm^2（801g）,供肝／受者体重比为1．3％。供肝之肝右、中静脉整形后与受者整形后之肝右静脉行端-侧吻合;供受者门静脉、肝动脉行端．端吻合。供肝胆管整形后与受者胆总管行端-端吻合。结果供、受者手术均成功。供者术后恢复顺利,受者术后8h恢复意识,14d后丙氨酸转氨酶、总胆红素等指标首次下降至正常水平。术后16d曾出现转氨酶明显升高,给予甲泼尼龙1000mg冲击治疗后恢复正常。随访至今,供受者已健康生存8个月,均未出现胆管、肝动脉及静脉回流等并发症。结论扩大右半肝移植在技术上完全可行。能为成人患者提供足够重量的移植物,尤其对于急性肝功能衰竭患者具有重要意义,术前精确的影像学评估,熟练的肝切除和肝移植技术是确保该类手术成功的关键因素。     

活体右半肝移植的流出道重建21例

目的 探讨活体右半肝移植中的流出道重建技术,预防肝静脉淤血的发生.方法 回顾分析21例成人活体右半肝移植的临床资料.供者标准肝体积为1150.1～1629.8 cm3,供肝重量为585～920 g,与受者标准肝体积比为43%～67%,与受者重量比为0.82%～1.59%,供者残肝体积百分比为32%～55%,供肝大泡脂肪变性均＜10%.对于含肝中静脉的供肝,将肝中静脉和肝右静脉开口修整成尽可能大的三角形开口,供肝植入时,与受者肝右静脉扩大的三角形开口行端侧吻合.不含肝中静脉的供肝,如存在粗大的肝中静脉属支(直径超过5 mm),则用自体或异体血管搭桥(无粗大的肝中静脉属支者采用肝右静脉)与受者腔静脉直接吻合.供肝门静脉右支直接与受者门静脉主干吻合,供肝动脉与受者肝动脉行端端吻合,供肝右肝管与受者肝管行端端吻合.结果 21例供肝中,4例含肝中静脉,17例不含肝中静脉,其中有2例采用自体大隐静脉搭桥,5例采用冷冻的异体髂动脉搭桥,10例采用肝右静脉直接与受者腔静脉吻合.术后1个月,重建肝中静脉属支的7例受者流出道均通畅.含肝中静脉者、不含肝中静脉的血管搭桥者及不含肝中静脉且未使用血管搭桥者术后1年存活率分别为75%、85.7%和70%,三者间比较,差异均无统计学意义(P＞0.05).术后受者发生胆道并发症7例;发生小肝综合征1例,经脾动脉栓塞治疗后痊愈.术后供者未发生严重并发症,随访6～31个月,均恢复正常工作生活,无一例死亡.结论 含肝中静脉与不含肝中静脉的右半供肝植入后均可取得良好的临床效果.如果右半供肝不含肝中静脉,采用自体或异体血管重建肝中静脉属支是预防肝淤血和保证移植肝功能的有效方法.     

Temporary auxiliary liver transplantation from a living donor to an adult recipient with familial amyloid polyneuropathy

A 33-year-old patient with familial amyloid polyneuropathy (FAP) underwent temporary auxiliary partial orthotopic liver transplantation (APOLT) from a living donor with a small-for-size graft. The auxiliary left lobar graft, which weighed only 230 g, was orthotopically transplanted after resection of the recipient's left lobe. The right portal vein was transected to induce compensatory hypertrophy of the left lobar graft. Posttransplant computed tomography showed atrophy of the native liver and hypertrophy of the graft, the volume of which had increased to 446 ml by postoperative day 41. The remnant native liver was removed 6 weeks after APOLT, and there were no signs of liver dysfunction during the postoperative course. Our experience with this case suggests that temporary APOLT is the treatment of choice, guaranteeing a sufficient margin of safety for both donor and recipient, in living donor liver transplants for FAP where the donor's left lobe is disproportionately small.     

原位肝移植的常用手术方式及应用体会

目的探讨经典原位肝移植术、改良背驮式肝移植术、原位肝移植腔静脉成形术在临床应用中的利弊。方法对2001年10月至2004年5月实施的155例病人的159次肝移植术式进行回顾性分析，其中经典原位肝移植术94例，改良背驮式肝移植术48例（包括改良背驮＋术中门一腔静脉端侧吻合转流8例），原位肝移植腔静脉成形术17例；术中行血管架桥5例，其中因门静脉闭锁及栓塞行供肝门静脉与受体肠系膜上静脉间架桥2例，因动脉变异分支细小不能利用行供肝腹腔干与受体腹主动脉间架桥3例。159例次肝移植手术均未应用体外静脉转流技术。结果原位肝移植腔静脉成形术的手术时间、无肝期最短，术中失血输血量最少，其术中对循环和肾功能的影响与经典术式相仿。经典原位肝移植术与背驮式肝移植术相比流出道不畅发生率较低，总手术时间较短（平均少30min），但无肝期较长（平均长8min），术中及术后肾上腺出血发生率较高，对肾功能影响较大，三组术后ICU留置天数差异亦无显著性意义（P=0．542）。结论不同的肝脏移植术式各有其优缺点，术者的经验以及对术式的熟悉程度会影响手术方式的选择，从原则上讲，手术方式的选择应根据具体病情及术中情况而决定。