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

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。研究了PMWLP系统对猪FHF模型的影响。采用α - amantin和脂多糖门静脉灌注法建立猪FHF模型。注射药物9小时后，将FHF猪与PMWLP系统连接6小时（n=5）。在对照组猪（n=10）中，该回路未连接到猪全肝。经PMWLP处理的猪存活时间明显延长。虽然对照组猪逐渐出现低血压，但PMWLP治疗猪表现出心血管稳定。PMWLP治疗显著抑制肝酶、总胆汁酸、氨和甲硫氨酸的升高。PMWLP处理的猪肝细胞坏死和中性粒细胞浸润程度明显减轻。PMWLP系统延长动物生存期，预防心血管不稳定，减轻肝损伤，增强胆汁酸代谢，减少肝性脑病相关因子。

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. The effect of the PMWLP system in porcine FHF model was investigated. Porcine FHF model was established by the intraportal administration of alpha-amanitin and lipopolysaccharide. Nine hours after the drugs injection, the FHF pigs were connected to the PMWLP system for 6 hours (n=5). In control pigs (n=10), the circuit was not connected to the porcine whole liver. Animal survival was significantly longer in the PMWLP treated pigs. Although the control pigs developed hypotension progressively, the PMWLP treated pigs demonstrated a cardiovascular stabilization. The PMWLP treatment significantly suppressed the elevation of liver enzymes, total bile acid, ammonia, and metionine. The degrees of hepatocyte necrosis and neutrophil infiltration were remarkably lessened in the PMWLP treated pigs. The PMWLP system prolonged animal survival, prevented cardiovascular instability, attenuated liver injury, enhanced bile acid metabolism, and decreased the hepatic encephalopathy related agents.