Applying a PUF/hepatocyte spheroid packed-bed type artificial liver to a drug induced hepatic failure rat. - Improvement of the medical treatment effect by optimization of the system -

We developed a hybrid artificial liver (Type 1, module volume: 5.65 cm³) utilizing PUF/hepatocyte spheroid culture, 80% of hepatic failure rats which induced by intraperitoneal injection of 0.5 g/kg-rat D-galactosamine could be recovered by extracorporeal circulation including this module. Then, optimization of the system was tried to aim at recovering a severed hepatic failure rat. A module volume was scaling up from 5.65 cm³ to 18.8 cm³ at 3.3 times (Type 2) and an extracorporeal blood circulation flow rate and a module side plasma circulation flow rate were changed from 0.5 to 1.0 ml/min and from 3.0 to 45.0 ml/min, respectively. In the results, blood ammonia of the hepatic failure rats which induced by 0.75 g/kg rat D-galactosamine (PT=35.9 sec, normal value=20 sec) were well metabolized and four rats were recovered out of five by using a Type 2 module (recovery ratio is 80%). But the rat was died by using a Type I module. On the contrary, blood ammonia concentration was dramatically increased in the control experiments, and three rats were died out of four by using a Type 2 module (recovery ratio is 25%). From the above, it seems that the optimized artificial liver support system is effective for recovering the severer hepatic failure rats.