Organ Changes and Bacterial Translocation in a Rat Model of Chronic Rejection After Small Bowel Transplantation Y. Zou, F. Hernandez, E. Burgos, L. Martinez, S. Gonzalez-Reyes, V. Fernandez-Dumont, G. Lopez, M. Romero, M. Lopez-Santamaria, and J.A. Tovar ABSTRACT Rejection after small bowel transplantation (SBTx) may allow bacterial translocation damaging the liver and lungs. This study investigated these issues in a rat model of chronic rejection. Materials and Methods. Orthotopic SBTx was performed in syngeneic (SYN) (ACI- ACI, n = 8) and allogeneic (ALLO) (ACI-Lewis, n = 8) rat strain combinations. Cyclosporine was given to ALLO rats for 28 days. Animals were sacrified between 55 and 65 days. Lymph nodes and venous samples were cultured; Escherichia coli DNA was assessed by polymerase chain reaction. We measured intestine, liver, spleen, and lung protein and DNA contents. Chronic rejection was histologically confirmed. Results. Two of eight and four of eight rats died in the first week after SYN and ALLO SBTx, respectively. There were no differences in organ weights or DNA and protein contents compared with the controls. Gram-negative enteric bacteria were found in two of four ALLO and two of six SYN rats (ns), and aerobic gram-positive were found in two of four and two of six (ns), respectively. Anaerobic growth occurred in mesenteric lymph nodes in only one ALLO rat. E. coli DNA was negative in all animals. Lungs were severely emphysematous in ALLO rats with no histologic changes observed in the other phagocytic organs. Mild rejection was found in the intestine of ALLO rats. Conclusions. Bowel lesions in ALLO rats might be consistent with chronic rejection and lung lesions could be related to bacterial translocation after SBTx. However, contrary to our expectations, no significant bacterial translocation was demonstrated in either group at the end of the experiments. B ACTERIAL TRANSLOCATION (BT) following small bowel transplantation (SBTx) is likely involved in the high incidence of sepsis, multiple organ failure, and mortality associated with this procedure. Long ischemia-reperfusion times, the inclusion of colon in the graft, and potent immunosuppression have been demonstrated to increase BT in clinical and experimental studies. 1,2 However, few studies have assessed BT at the onset of chronic rejection. The present study sought to investigate the structure of the intestine and phagocytic organs as well as the presence of BT in a model of chronic rejection. MATERIALS AND METHODS Animals Orthotopic SBTx was performed in syngeneic (SYN) (ACI-ACI, n = 8) and allogeneic (ALLO) (ACI-Lewis, n = 8) rat strain combinations. Intramuscular cyclosporine (15 mg/kg, days 0 to 6 and 8 to 28) was injected to ALLO rats for 28 days and then ceased, a dosage based on a previously described model of chronic rejection. 3 Saline was used instead in the control group. The animals were housed in our facilities that are accredited by regional animal health authorities in compliance with the current European From the Department of Pediatric Surgery (Y.Z., F.H., L.M., S.G.-R., V.F.-D., M.L.-S., J.A.T.), Department of Pathology (E.B.), and Department of Bacteriology (G.L., M.R.), Hospital Universi- tario, La Paz, Madrid, Spain. Supported by grant CAM 08.3-6-2003 1 of Comunidad de Madrid. Address reprint requests to Prof Dr Juan A. Tovar, Department of Pediatric Surgery, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain. E-mail: jatovar.hulp@ salud.madrid.org © 2006 by Elsevier Inc. All rights reserved. 0041-1345/06/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2006.03.025 Transplantation Proceedings, 38, 1569 –1572 (2006) 1569