Efficacy of Double Filtration Plasmapheretic Cross Circulation with a High Permeability Membrane using Porcine Whole Liver on Fulminant Hepatic Failure Model in Macacus rhesus monkey

在使用生物人工肝装置时，需要制备足够的肝细胞团以提供足够的代谢支持，减少异种免疫反应，并避免病毒传播。我们开发了半渗透膜血浆置换结合全肝灌注系统（PMWLP），它提供了大量的功能性肝细胞，免疫保护和病毒传播的屏障。为了评价体外全肝功能和跨膜分子运动，用含有葡聚糖、氯化铵、D-半乳糖和利多卡因的液体循环完整的PMWLP系统6小时。循环6小时后，氨、D-半乳糖和利多卡因的总量显著消除。体外猪全肝产生尿酸。全肝耗氧量维持在0.25-0.26ml/100 g肝/min，持续6小时。白蛋白可自由通过膜，而IgM不能通过。门静脉注射α-鹅膏蕈碱和脂多糖建立猴暴发性肝衰竭（FHF）模型，但α-鹅膏蕈碱和脂多糖不能造成肝损伤。目前，PMWLP系统在猴肝热缺血再灌注2小时FHF模型中的作用正在研究中。已证实PMWLP系统改善了动物存活时间。

In the use of bioartificial liver devices, preparation of sufficient liver cell mass to provide adequate metabolic support, reduction of xenogeneic immune reaction, and avoidance of viral transmission are required. We developed a plasmapheresis using semipermeable membrane combined with whole liver perfusion(PMWLP) system, which offered a large number of functional liver cells, an immunoprotection, and a barrier to the viral transmission. To evaluate the extracorporeal whole liver function and molecular movement across the membrane, a complete PMWLP system was circulated with fluid containing dextran, ammonium chloride, D-galactose, and lidocaine for 6 hours. After 6 hours circulation, total volume of ammonia, D-galactose, and lidocaine were significantly eliminated. Uric acid was produced by the extracorporeal porcine whole liver. Oxygen consumption of the whole liver was maintained at 0.25-0.26ml/100g liver/min for 6 hours. Albumin freely moved across the membrane, whereas IgM could not pass.The monkey fulminant hepatic failure(FHF) was designed to be established by an intraportal administration of alpha-amanitin and lipopolysaccharide However, the alpha-amanitin and lipopolysaccharide, unfortunately, could not make liver injury. Presently, the effect of the PMWLP system in monkey FHF model which are induced by 2-hour hepatic warm ischemia reperfusion is investigating. It has been confirmed that the PMWLP system improved the animal survival time.