Efficacy of double-filtration plasmapheretic cross-circulation with a high-permeability membrane using canine harvested liver in porcine fulminant hepatic failure model

Abstract 

Introduction

The use of bioartificial liver devices requires. A sufficient liver cell mass to provide adequate metabolic support, reduction of xenogeneic immune reactions, and avoidance of viral transmission. We have developed a plasmapheresis system using a semipermeable membrane combined with canine whole liver perfusion (PMCWLP). In this study, we investigated the efficacy of our system in a porcine fulminant hepatic failure (FHF) model.

Methods

The porcine FHF model was established by intraportal administration of alpha-amanitin (0.1 mg/kg) and lipopolysaccharide (1 μg/kg). Nine hours after drug injection, xenogenic perfusion treatment was performed twice within 6 hours (n = 5). As the plasmapheresis device, we used a hollow-fiber module with cellulose diacetate porous fibers (pore size, 0.05 μm, surface area, 2 m²). The canine whole liver was perfused with modified Krebs solution, which is commonly used in many laboratories, containing albumin (2 g/dL) and glucose (300 mg/dL). Control pigs (n = 10), had the circuit not connected to the whole canine liver.

Results

The survival of FHF pigs was significantly increased by the treatment (58.9 ± 21.8 hour) compared with the controls (22.3 ± 8.1 hour). Mean blood ammonia levels and intracranial pressure during treatment were significantly lower compared with control groups.

Conclusion

Treatment of FHF pigs with the system significantly increased survival time, suggesting that this method may have applications as a clinical liver assist device.