Liver xenotransplantation: changes in lipid and lipoprotein concentration after long-term graft survival

Background/Aims: Today, scientists devote considerable effort to the study of mechanisms of xenograft rejection, but with liver xenotransplantation (X Tx) researchers face the added problem of metabolic incompatibility between species. To date, there have been few studies of molecular xenogeneic inte ractions, perhaps because little progress has been made in solving immunolo gical problems. This study is an initial analysis of lipoprotein metabolism in a hamster-to-rat hepatic xenotransplantation model. Methods: There were 6 experimental groups (n=8): (1) male Sprague-Dawley (S .D.) rats (220-280 g); (2) male Golden Syrian hamsters (100-150 g); (3) S.D . rats, "sham" operation with immunosuppression; (4) S.D. rat-to-S.D. rat a lloTx; (5) S.D. rat-to-S.D. rat alloTx with immunosuppression; (6) XTx hams ter G.S-to-S.D. rat with immunosuppression, Mofetil mycophenolate (25 mg/kg /d) was administered for 14 days and FK506 (0.2 mg/kg/d) for 45 days (group s 3, 5 and 6), After 24 h fasting, animals were sacrificed (day +50 postran splantation) and a complete lipoprotein profile was determined, Serum lipop roteins were subfractioned by ultracentrifugation in density gradient. Results: There was a large increase in serum lipid levels in xenografted ra ts compared with control rats and allografted rats. Xenografted rats presen ted a severely altered lipoprotein profile compared with normal rats. Surpr isingly, the characterisation of lipoproteins in xenografted rats displayed the same composition as donor animals. Histological study did not show sig ns of alteration of the hepatic architecture. Conclusions: Since the liver is the main solid organ co-ordinator of metabo lic pathways, such as lipid metabolism, hepatic xenotransplantation makes c hanges in lipid concentrations in the recipient and also changes in lipid c ompositions of lipoproteins, Hepatic xenotransplantation is not a feasible solution given the organ's metabolic complexity.