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，避免病毒传播。我们开发了一种采用半透膜结合全肝灌注（PMWLP）系统的血浆置换，该系统提供了大量功能性肝细胞，具有免疫保护作用，并对病毒传播形成了屏障。为了评估体外全肝功能和分子跨膜运动，将一个完整的PMWLP系统与含有葡聚糖、氯化铵、d -半乳糖和利多卡因的液体循环6小时。循环6小时后，氨、d -半乳糖和利多卡因的总容积明显消失。尿酸是由体外猪全肝产生的。全肝耗氧量维持0.25 ~ 0.26ml/100g肝/min，持续6小时。白蛋白可以自由地穿过细胞膜，而IgM则不能通过。本研究旨在通过静脉注射α - amantin和脂多糖来建立猴暴发性肝衰竭（FHF），但不幸的是，α - amantin和脂多糖不会造成肝损伤。目前，我们正在研究PMWLP系统对2小时肝热缺血再灌注诱导的猴FHF模型的影响。已经证实，PMWLP系统提高了动物的生存时间。

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.