title: Orthotopic liver/small bowel transplantation in rats: a microsurgical model inducing tolerance.
abstract: Liver cirrhosis in patients with short bowel syndrome is successfully treated in humans by simultaneous liver/small bowel transplantation. However, until now, a clinically relevant experimental rat model for this procedure has not existed. We therefore established a protocol that, for the first time in rats, allows the simultaneous transplantation of arterialized liver and small bowel into an orthotopic position. Short-term immunosuppression induced not only allograft acceptance but tolerance (as demonstrated by indicator heart/skin transplantation). The immunosuppressive dose required to achieve this result was dramatically less than that of protocols for successful small bowel transplantation alone. Immunohistochemistry detected a transient rejection crisis before tolerance. During this crisis, apoptotic recipient-type T lymphocytes, mainly CD8+ cells, accumulated in the liver but not in the small bowel allograft. The initiation of T-cell apoptosis is one possible explanation for the specific immunosuppressive effect of the liver allograft, which also supports the simultaneously transplanted small bowel allograft in our model.
authors.affiliation: Department of Surgery, University of Würzburg, Josef-Schneider Strasse 2, D-97080 Würzburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Meyer
authors.forename: W M
authors.initials: WM
authors.lastname: Thorwarth
authors.forename: C
authors.initials: C
authors.lastname: Otto
authors.forename: H J
authors.initials: HJ
authors.lastname: Gassel
authors.forename: W
authors.initials: W
authors.lastname: Timmermann
authors.forename: K
authors.initials: K
authors.lastname: Ulrichs
authors.forename: A
authors.initials: A
authors.lastname: Thiede
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology; D008866:Microsurgery; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus