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

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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.