DISCORDANT LIVER-TRANSPLANTATION IN THE GUINEA-PIG TO RAT MODEL DOES NOT LEAD TO CLASSICAL HYPERACUTE REJECTION

Discordant grafting, the best alternative for future transplantation, is hampered by hyperacute rejection (HAR). Yet, there might be a diffe rence in susceptibility to HAR between organs. In allogeneic transplan tation the liver is less sensitive to antibody mediated rejection. In order to investigate whether this might also occur in discordant xenot ransplantation, we performed orthotopic liver transplantation (OLT) fr om Dunkin Hartley guinea pigs (GP) to Brown Norway rats. Five groups w ere studied. In group 1, untreated controls survived for 1.5 to 4.5 hr (n = 5). In order to investigate how long a recipient could survive w ithout a functioning graft, animals in group 2 underwent total hepatec tomy (tHx) with portal-caval shunt, resulting in survival times rangin g from 2 to 7 hr (n = 5). Antibody reduction by splenectomy (Spx) on d ay -5 (group 3) did not increase survival time (1 to 2 hr, n = 5). Com plement depletion by cobra venom factor (CVF) prolonged the survival t ime up to 35 hr (n = 7, group 4). One animal lived for 4 days. The com bined treatment of Spx and CVF resulted in similar survival times as f ollowing CVF alone, ranging from 2 hr to 6 days (n = 6, group 5). Surp risingly, none of the grafts in either of the groups showed classical signs of hyperacute rejection, like hemorrhage, edema, or obstruction of capillaries and veins as seen in the GP to rat heart transplantatio n model. Also liver enzyme parameters indicated no ongoing rejection. Immunohistochemistry revealed deposits of complement factors C1q, C3, and C6 on Kupffer cells but not on endothelial cells. These results in dicate that, in this particular discordant model, the liver is not aff ected by the classical features of HAR. The beneficial effect of CVF o n recipient survival therefore may rather be due to inhibition of a le thal secondary response evoked by the graft than to inhibition of HAR.