P0770 INTESTINAL ABSORPTIVE FUNCTION AFTER ORTHOTOPIC INTESTINAL TRANSPLANTATION: AUGMENTATION BY GLP-2

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Introduction: Advances in surgical technique, medical management, immunosuppression and surveillance have resulted in improved outcomes for patients undergoing intestinal transplantation (IT). Although it is known that intestinal absorptive function is not normal after transplant, few studies have been done investigating absorptive function of the intestinal graft. It is also not known whether peptide intestinal growth factors that have been shown to enhance intestinal absorptive functions effect the intestinal graft post –transplant. Methods: A rodent model for orthotopic IT was established in our laboratory using Brown-Norway rats as donors and Lewis rats as recipients. Immunosuppression was with tacrolimus give at 1 mg/kg daily. In order to investigate whether glucagons-like peptide-2 (GLP-2) acts on transplanted bowel, 3 animal groups were studied: Unoperated controls (UC), IT receiving normal saline injections (IT-NS) and IT receiving GLP-2 injections .2 mg/kg/dose twice per day (IT-GLP2). IT animals were pair-fed. Intestinal absorptive function was studied by measurement of hydrogen excretion using sucrose as substrate on POD#10. On POD#14, animals were killed and the intestines removed for analysis. Results: After IT, animals tolerated solid food within 2 days, groomed normally and gained wt. No diarrhea or other evidence of graft rejection was noted. Study survival, including surgical mortality, was 78%. As noted in Table 1, hydrogen excretion after sucrose administration was greatest in IT-NS, and significantly less in IT-GLP2, indicating improved carbohydrate absorption in this animal group. Hydrogen excretion was lowest in UC. Biochemical analysis showed intestines of IT-GLP2 to have increased wt/length, increased mucosal wt/length and increased DNA contests in ileal segments with no differences noted in jejunal segments as compared with IT- NS.Table 1Conclusion: 1) An animal model for orthotopic intestinal transplantation was successfully established in our laboratory. 2) In spite of no clinical evidence for rejection or malabsorption, intestinal absorptive function, as measured by carbohydrate absorption, is impaired following IT. 3) Exogenous administration of GLP-2

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