In vitro evaluation of cross-circulation system using semipermeable membrane combined with whole liver perfusion

Many types of isolated hepatocytes-based bioartificial liver have been developed. However, to maintain hepatocyte-specific functions for a long period is still a significant challenge. The possibilities of rejection or viral transmission still remain as untackled obstacles. We developed a cross-circulation system, using a semipermeable membrane combined with whole liver perfusion. Detoxifying functions of the extracorporeal porcine liver and molecular movements across the membrane were evaluated in vitro.

The hollow-fiber module has a molecular cutoff of 100 kD. A spiked solution containing 500 mL low molecular dextran solution spiked with 12 mg ammonium chloride, 500 mg D-galactose, and 300 mg lidocaine, which mimicked a patient, was recirculated through the inner fiber space. The extracorporeal liver perfusion circuit consisted of an extra-fiber spaces. A reservoir containing 1000 mL healthy pig plasma, a membrane oxygenator, and a porcine whole liver. Both circuits circulated in the opposite direction for 6 hours.

In 6 hours, 47.3% +/- 10.2% of ammonia, 89.5% +/- 1.7% of D-galactose, and 95.5% +/- 1.0% of lidocaine were eliminated from the circuits; 66.5 +/- 11.1 mg of urea were produced at the same time. Oxygen consumption was maintained between 0.248 and 0.259 mL/100 g liver/min for 6 hours. Movement of IgM was completely blocked by the 100-kD membrane, whereas albumin was freely transferred from the reservoir to the intrafiber space.

The perfusion experiments showed the possibility of using a whole liver with oxygenated plasma perfusion in a bioartificial liver system in vitro.