Amino acid and lipid profiles following pig-to-primate liver xenotransplantation.

Abstract

As outcomes in clinical liver transplantation steadily improve, demand continues to exceed supply, leading to a substantial disparity in organ availability. The translation of porcine liver xenotransplantation (LXT) into a clinical reality aims to address this dilemma. Our laboratory has previously established an applicable model of α-1,3-galactosyltransferase knockout (GalT-KO) pig-to-primate LXT with continuous human coagulation factor infusion and costimulation blockade. This report aims to further investigate the post-LXT lipid and amino acid metabolism profile in our longest surviving recipients (25 and 29days). Experimental samples and control samples, consisting of pre-transplant porcine and baboon serum and plasma, were analyzed for standard lipid profiles and for amino acid levels. Lipid profiles of LXT recipients remained stable following xenotransplantation compared to donor porcine baseline levels. Amino acid concentrations also remained similar to baseline controls, with the exception of a 3-fold increase in l-ornithine and more than a 10-fold decrease in l-arginine post-transplant when compared to both porcine and baboon baseline levels. The observed changes in l-arginine are consistent with prior studies investigating the effects of graft preservation injury following liver transplantation. These results indicate that the porcine liver can maintain most biochemical profiles stably post-operatively in baboons and suggest that arginine supplementation post-LXT may potentially be useful for further prolongation of xenograft survival.