Background.A major obstacle to successful small bowel transplantation is that of bacterial infection. The aim of this study was to preserve the small bowel mucosal barrier by using oxygenated luminal perfusion with a proven amino acid (AA)-based solution.Methods.Rat small bowel (n=4) was flushed vascularly with modified University of Wisconsin solution and flushed luminally as follows: group 1, none (control); group 2, AA solution; group 3, 1-hr perfusion then storage with AA; group 4, continuous perfusion with AA. Energetics, malondialdehyde (MDA), glutathione (reduced), and histology were assessed over 24 hr at 4°C.Results.Within 4 hr, adenosine triphosphate (ATP) dropped by 25% to 65% in all groups except for group 4, which remained unchanged from fresh tissue values throughout 12 hr. After 12 hr, ATP in groups 1 through 3 had dropped to 0.5 to 0.9 &mgr;mol/g, compared with 1.5 &mgr;mol/g for group 4. Even after 24 hr, group 4 levels were more than twofold greater than groups 1 through 3. MDA increased transiently in tissues subjected to simple flush (no perfusion), whereas levels in perfused tissues remained elevated throughout the 24-hr period. Glutathione in group 1 dropped by greater than 50% from fresh tissue values but increased over 24 hr in groups 2 and 3 by 50% to 55%. Overall, histologic injury was markedly less in groups 2 through 4; however, after 24 hr, the lowest injury was observed in group 3 (median, grade 2) compared with groups 1 and 4 (grades 7 and 4).Conclusions.Our data indicate that perfusion clearly improves tissue energetics. However, mucosal integrity is markedly superior, with only a brief 1-hr period of perfusion; oxidative and mechanical stress are the factors likely responsible for injury resulting from continuous perfusion.