APPLICATION OF IMMUNOAPHERESIS FOR DELAYING HYPERACUTE REJECTION DURING ISOLATED XENOGENEIC PIG-LIVER PERFUSION

Background. Extracorporeal liver perfusion in hepatic coma, used to el iminate toxic metabolites causing hepatic encephalopathy, is limited b y the antibody (Ab) and complement-mediated hyperacute rejection of di scordant xenografts, Thus, the efficacy of highly selective immunoadso rption columns to deplete xenoreactive human anti-porcine antibodies b efore ex vivo liver perfusion was examined in this study. Methods. Eig hteen domestic pigs were hepatectomized according to standard techniqu es, The livers were ex vivo perfused for 4 hr, The perfusion protocol closely followed the physiological conditions of a human liver, Parame ters of liver function and damage were analyzed, Three groups were for med differing in the treatment of the perfusate, As basic control, liv ers were perfused with heparinized human blood (group 1; n=6), Immunoa pheresis was applied in group 3 (n=6), Immunoapheresis was performed u sing Ig Therasorb columns consisting of sheep-anti-human IgG Abs coval ently coupled to Sepharose CL-4B, Additionally, the effect of pure Sep harose CL-4B without immobilized Ab was tested in group 2 (n=6). Resul ts. The use of Ig Therasorb 100 columns in group 3 resulted in a reduc tion of IgG, IgM, and IgA in the order of 95.0%, 72.3%, and 81.5%, res pectively, In group 2, IgG, IgM, and IgA were lowered by 30% to 39%, D etermination of liver-specific enzymes and tolerance tests revealed a significant reduction of cellular damage and functional restrictions i n group 3 compared with the control groups. Conclusions. Immunoapheres is conducted according to this protocol appears to be an effective app roach for delaying antibody-mediated hyperacute xenogeneic rejection.