Efficacy of double filtration plasmapheretic cross-circulation using a high permeability membrane between totally hepatectomized dogs and donor pigs.

ABSTRACT

BACKGROUND: Major obstacles to develop a bioartificial liver are xenogeneic immune reactions and viral infection from donor pigs. To solve these problems, we studied the effect of xenogeneic double filtration plasmapheretic cross-circulation (DFPCC) using a high performance semipermeable membrane on totally hepatectomized dogs. METHODS: Mongrel dogs, weighing 12-15 kg, underwent total hepatectomy in one stage (n=18). One hr after total hepatectomy, the femoral vein and the jugular vein were cannulated in both dogs and pigs by using the blood access catheter tubes that were connected to the DFPCC system. In the DFPCC circuit, filtrated dog plasma and pig plasma counterflowed in a hollow fiber cartilage at a rate of 25 ml/min for 6 hr and met through a semipermeable membrane with 100 kd nominal molecular weight cut-off (n=5). In control dogs, the circuit was not connected to the pig (n=13). RESULTS: In vitro mass transfer study suggested that very little immunoglobulins crossed the semipermeable membrane. During and after 6 hr of DFPCC, anhepatic dogs had significantly lower blood ammonia and aromatic amino acid levels than did controls. DFPCC-treated dogs demonstrated decreased intracranial pressure and survived significantly longer than control dogs (20.75+/-3.80 hr vs. 14.75+/-1.30 hr, P<0.05). Histology showed no xenogeneic rejection in both dogs and pigs. CONCLUSIONS: Our DFPCC systems with a high permeability membrane demonstrated detoxification-function and contributed to intracranial decompression and longer animal survivals without adverse immune reaction and the possibility of zoonosis.