猪辅助性异位部分肝移植

目的 探讨辅助性异位部分肝移植治疗急性缺血性肝衰的效果。方法 用家猪配对行辅助性异位部分肝移植治疗急性缺血性肝衰。随机分为两组：I组，受体肝脏保持原状，肝动脉结扎，门静脉缩窄，供肝右半肝植入受体右肝下，仅建立门静脉血供，不建立动脉血供；Ⅱ组，供肝动脉和门静脉均建立血供，其它手术内容与I组相同。监测各组受体存活情况、肝功能、肝脏血流情况、病理及供肝胆汁分泌情况。结果 Ⅱ组受体成活率显著高于I组。I组术后胆红素显著高于术前，Ⅱ组手术前后胆红素无显著变化，I组术后胆红素显著高于Ⅱ组。I组供肝无或仅有少量胆汁分泌，肝细胞大片坏死；Ⅱ组供肝胆汁分泌和血供良好，肝细胞存活良好并有活跃的代偿性增生；I，Ⅱ组自体肝脏均大片坏死。结论 受体肝动脉结扎、门静脉缩窄能造成急性缺血性肝衰。辅助性异位部分肝移植可以治疗肝衰，效果良好。供肝必需建立良好的动脉血供。     

猪辅助性异位部分肝移植动脉重建的方法及意义

２００１年１月～７月,我们进行了猪的同种异体辅助性异位部分肝移植（ＡＨＰＬＴ）实验,现将实验情况与供肝动脉重建有关的内容总结如下。材料与方法１．实验动物健康家猪１５头,体重２５～３５ｋｇ,雌雄不限,供受体配对移植。２．手术方式按手术模式不同分两组：Ａ组：共８头,受体肝脏保持原状,其门静脉捆扎缩窄８５％以上（直径缩窄至１／３）,肝动脉结扎;供肝（右半肝）植入受体右肝下,其肝动脉结扎,下腔静脉与受体肝下下腔静脉行端侧吻合,门静脉与受体肠系膜上静脉或门静脉行端侧吻合,胆总管与受体空肠行端侧吻合（内置Ｔ…     

动脉血供对异位移植肝功能影响的实验研究

实验和临床异位肝移植都强调门静脉血供的重要性。但实验性肝移植的不同结果，对是否重建移植肝的动脉血供尚有争议。为探索动脉血供对异位移植肝功能的影响，我们以从美国引进的同窝迪卡猪为实验对象，分两组进行对比研究，行减体异位肝移植。结果表明，有门静脉和肝动脉双重供血的异位肝，在血液循环恢复后立即有胆汁分泌。仅有门静脉供血、无动脉供血的异位肝一直无胆汁分泌，且逐渐萎缩。这一结果提示，异位肝移植应重视重建门脉和动脉双重供血。证实了动脉血供对异位移植肝功能的影响。     

猪辅助性异位部分肝移植供肝的修整和断面处理

目的：探讨辅助性异位部分肝移植（AHPLT）供肝的修整和断面处理方法。方法：按照猪肝脏的解剖结构，切除左半肝，将供肝右半肝植入受体右肝下，观察受体存活率，肝功能，供肝胆汁分泌情况及病理改变；分组按不同方法处理供肝断面，A组单纯缝扎，B超用大网膜衬垫后缝扎加医用胶涂布，观察断面的处理效果，分析总结。结果：1．用供肝右半肝植入的方法，行AHPLT的肝衰受体存活率和肝功能显著优于肝衰模型组，植入肝脏胆汁分泌和肝细胞存活良好。2．B组供肝断面的撕裂机率和出血率，腹腔出血率，出血所致的病死率均显著低于A组，结论：ALPLT时，用供肝右半肝植入是合适的；供肝断面应在衬垫下缝扎，并涂布医用胶。     

剥夺宿主肝部分门脉血供对异位植移肝和宿主肝的影响

异位移植肝易发生萎缩而失去其功能．认为是免疫排斥功能竞争和血供等多种因素所致。为了探索其主要因素，我们以美国的迪卡猪为实验对象，为了摒除排斥因素的作用，选用同窝猪作为供、受体，分2组进行部分异位肝移植。供肝切除左半肝，将右半肝植人受体右肝下．供肝肝上下静脉与受体肝下肾以上下腔静脉行端侧吻合。供肝动脉带一段胸主动脉与受体肾以下主动脉行端侧吻合．其中一组动物在血管重建后，缩窄受体门静脉，以剥夺宿主肝的部分血供；另一组不缩窄门静脉作为对照。实验结果表明，门脉缩窄组存活5d以上的猪，宿主肝均发生萎缩，井呈现明显的缺血外貌，而移植肝无一发生萎缩和缺血表现。未缩窄门静脉的一组动物，移植肝均发生萎缩，宿主肝无改变。结果提示，剥夺宿主肝部分门静脉血液供应，以保证异位移植肝的门脉血供是造成异位移植肝存活、宿主肝萎缩的有效措施，从而证实了异位移植肝发生萎缩的主要因素是门静脉供血问题。     

可量化的受体门静脉干预调节猪辅助性部分肝移植两肝门静脉血流竞争

目的 观察不同程度的受体肝门静脉缩窄对猪辅助性部分肝移植(APLT)受体肝和移植肝门静脉血流竞争的防治作用,探讨一种可量化的受体肝门静脉干预标准.方法 32头健康幼猪按体重相近原则配对,取右半肝作为供肝,切除受体肝左叶,共行16次APLT.根据移植后受体门静脉缩窄程度,将其分为4组:对照组(n=5,门静脉未行处理),缩窄1/4组(n=4,受体门静脉宽度缩窄1/4),缩窄1/3组(n=4,缩窄1/3)和结扎组(n=3,门静脉结扎).定期观察各组受体肝和移植肝的体积大小、血流状况及组织结构的变化.结果 术中电解质变化各组基本相似,血流动力学变化以对照组和缩窄1/4组较为平稳;各组存活率和最长存活时间均以缩窄1/4组最优;门静脉造影示缩窄1/4组两肝之门静脉均得到较好显影,未见明显造影剂淤积和血管扩张;多普勒超声示各组移植肝门静脉依次增宽,流速分别为0.220、0.293、0.336和0.400 m/s,受体门静脉流速分别为0.275、0.294、0.328和0 m/s;两肝体积、充盈度和包膜紧张度以缩窄1/4组最为适中,坏死程度亦以缩窄1/4组最轻.结论 在供受体体重相近且无明显肝硬化时,为防治APLT门静脉血流竞争,以受体门静脉宽度缩窄1/4较为适宜.     

不同预处理对大鼠肝移植供肝保护作用的探讨

目的 通过应用缺血、加热等多种手段对大鼠供肝进行移植术前的预处理,比较各种预处理方法对大鼠肝移植供肝缺血再灌注损伤的保护作用. 方法 将SD大鼠50只,随机分为5组:半肝缺血预处理组、脾脏缺血预处理组、热休克预处理组、热休克+缺血预处理组及手术对照组,分别进行肝脏预处理后行模拟原位肝移植术,术后检测胆汁流量,术后24 h检测血清ALT,AST,ALP水平并观察肝脏形态学变化. 结果 半肝缺血预处理组、热休克预处理组移植后胆汁分泌量多于对照组,血清ALT,AST水平明显低于对照组(P<0.05);热休克+缺血预处理组的血清ALT水平低于对照组(P<0.05),胆汁分泌量及血清AST与对照组没有显著差异;脾脏缺血预处理组的胆汁分泌量多于对照组,血清ALT水平低于对照组(P<0.05). 结论 肝脏缺血预处理初始阶段保护作用最明显,将缺血及热休克预处理两种方法联合处理大鼠时,其保护作用弱于单独缺血或单独热休克的预处理方法;脾脏缺血预处理也具有保护肝脏的作用.     

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。     

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。     

辅助性肝移植研究进展

辅助性肝移植足指住保留受体自身全部或部分肝脏的情况下,将供肝植入受体体内.根据供肝植入部位不同,可分为异位辅助性肝移植和原位辅助性肝移植;根据植入肝体积的多少,可分为全肝辅助性肝移植和部分肝辅助性肝移植;供肝可来源于脑死亡供体也可以来源于活体供体.山于原位辅助性肝移植只能移植部分肝脏,故通常称为原位辅助性部分肝移植.辅助性肝移植伴随着肝移植的发展而不断发展,虽然还存在许多尚待解决的问题,但辅助性肝移植独特的优势再次引起肝移植界的广泛关注.     

Directing portal flow is essential for graft survival in auxiliary partial heterotopic liver transplantation in the dog.

BACKGROUND/PURPOSE: Auxiliary liver transplantation is an attractive alternative for orthotopic liver transplantation in patients with certain inborn errors of metabolism of the liver in which complete resection of the liver is unnecessary or even contraindicated. Because in these diseases portal hypertension is mostly absent, finding a balance in portal blood distribution between native liver and graft is complicated. The objective of this study was to investigate requirements for long-term (180 days) graft survival in auxiliary partial heterotopic liver transplantation (APHLT) in a dog model. METHODS: A metabolic defect was corrected in 26 dalmation dogs with a 60% beagle heterotopic auxiliary liver graft. Four groups of different portal inflow were studied. In the ligation group the portal vein to the host liver was ligated. In the split-flow group graft and host liver received separate portal inflow. In the banding group the distribution of the portal flow was regulated with an adjustable strapband and in the free-flow group the portal blood was allowed to flow randomly to host or graft liver. RESULTS: Metabolic correction increased in all groups after transplantation from 0.19 +/- 0.02 to 0.70 +/- 0.05 (P< .0001) but remained significantly better in the ligation and split-flow groups (graft survival, 135 +/- 27 and 144 +/- 31 days). In the banding group metabolic correction decreased significantly after 70 days, and although the grafts kept some function for 155 +/- 14 days, in 4 of 6 dogs portal thrombosis was found. In the free-flow group, competition for the portal blood led to reduced correction within 12 days and total loss of function in 96 +/- 14 days. Graft function also was assessed with technetium (Tc) 99m dimethyl-iminodiacetic acid uptake. A good linear association between HIDA uptake and metabolic correction was observed (r = 0.74; P < .0005). Grafts that contributed more than 15% to the total uptake of HIDA showed biochemical correction. This indicates a critical graft mass of about 15% to 20% of the hepatocyte volume to correct this metabolic defect. CONCLUSION: Auxiliary partial heterotopic liver transplantation can be a valuable alternative treatment for inborn errors of hepatic metabolism if the native liver and the graft receive separate portal blood inflow.     

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.     

Rat auxiliary liver transplantation without portal vein reconstruction: comparison with the portal vein-arterialized model

Auxiliary liver transplantation (ALT) has been reintroduced in clinical cases recently and is now believed to be a viable alternative to orthotopic liver transplantation. To provide a simple rat ALT model for studying the physiological and immunological aspects of the ALT graft, a new ALT was performed, and the comparison between this new model and the portal arterialized one that was reported by other investigators was carried out. At first, we confirmed that liver could tolerate the deprivation of its portal flow well, using a portosystemic shunted rat model. The new rat ALT model, in which the ALT graft obtained its blood inflow only from the hepatic artery, was then performed. Our results demonstrated that 50% of the hepatic artery-alone ALT graft showed almost normal structure histologically at 1 month after grafting, with bile secretion preserved. By contrast, only 8% 1-month graft survival was noted in the portal arterialized group, and all grafts stopped bile secretion 1 week after operation. In conclusion, with arterial blood supply alone, the ALT graft survived and demonstrated normal bile secretion function for more than 1 month. Portal vein arterialization is not an appropriate way to establish the graft's blood supply if no pressure adjustment measures were taken in advance.     

Auxiliary heterotopic partial liver transplantation in pigs with acute liver failure

Fulminant hepatic failure is usually fatal without liver transplantation; however, orthotopic liver transplantation is often difficult to perform due to the high risk of coagulopathy and the development of multiple organ failure. Auxiliary heterotopic partial liver transplantation (APLT), however, has the potential to provide an effective hepatic support system considering that the host liver is left in situ and the surgical procedure is less invasive. In this report, we describe the beneficial effects of performing 60% APLT on the hepatic function and survival of pigs with acute hepatic failure induced by hepatic artery ligation. The pigs were divided into a control group of nine animals (group 1) that had portal vein and hepatic artery ligation with a side-to-side portacaval shunt, and an APLT group of seven animals (group 2) that had portal vein and hepatic artery ligation with APLT. The two left lateral lobes of the donor liver were resected, reducing the liver weight to about 60%, and the graft was placed in the right subhepatic space. No deaths occurred intraoperatively. In group 1, eight pigs died of massive liver necrosis within 48 h and one died between 48 and 72 h (median surivival 23 h). In group 2, two pigs died within 72 h due to preservation or anesthetic problems, but five survived for more than 3 days (median survival 13.4 days), with a significant difference between the two groups (P<0.05). One animal was killed 30 days after APLT and excellent graft function was demonstrated by the synthesis of clotting factors, ammonia detoxification, and glucohomeostasis. Moreover, evidence of hepatic regeneration was found in the transplanted livers. These results indicate that APLT provides metabolic support and improves survival in animals with induced acute liver failure.     

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.     

Outcome and Hepatic Hemodynamics in Liver Transplant Patients with Portal Vein Arterialization

Few cases of successful portal vein arterialization in orthotopic and auxiliary liver transplantation have been reported. AIM: To evaluate the effect of portal vein arterialization on hepatic hemodynamics and long-term clinical outcome in three patients undergoing liver transplantation. METHODS: Two patients with extensive splanchnic venous thrombosis received an orthotopic liver transplant and one with fulminant hepatic failure received an auxiliary heterotopic graft. Portal vein arterialization was performed in all cases. RESULTS: One patient died 4 months after transplant and two are still alive. Auxiliary liver graft was removed 3 months post-transplant when complete native liver regeneration was achieved. Immediate post-transplant liver function was excellent in all cases. Only one patient developed encephalopathy and variceal bleeding owing to prehepatic portal hypertension secondary to arterioportal fistula 14 months after transplant. He was successfully treated by embolization of the hepatic artery. Hepatic hemodynamic measurements demonstrated a normal pressure gradient between wedged and free hepatic venous pressures in all cases. Liver biopsy showed acceptable graft architecture in two cases and microsteatosis in one. CONCLUSIONS: Liver transplantation with portal vein arterialization is an acceptable salvage alternative when insufficient portal venous flow to the graft is present. The double arterial supply does not imply changes in hepatic hemodynamics, at least in the early months post-transplant.     

猪辅助性异位部分肝移植术的三种模式对比

目的：探讨猪辅助性异位部分肝移植术最佳模式。方法：28头幼猪随机分成供体组和受体组，分A、B、C三种模式进行异位部分肝移植。结果：C组模式从解剖学、血流动力学角度均优于A、B两组。结论：C组模式优于A组和B组模式。     

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