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Title: Bacterial translocation during graft-versus-host disease after small bowel transplantation is reduced following inhibition of inducible nitric oxide synthesis. Author: Langrehr JM, Machens C, Zill E, Leder K, Nüssler A, Hoffman R, Neuhaus P. Journal: Transplantation; 2000 Jun 15; 69(11):2415-21. PubMed ID: 10868651. Abstract: BACKGROUND: Increased nitric oxide (NO) production may contribute to intestinal barrier dysfunction and increased bacterial translocation (BT). Since BT may play a major role in graft-versus-host disease (GVHD) after small bowel transplantation (SBTx), we evaluated the role of NO production in GVHD after SBTX in the rat. METHODS: Using the standard model of semiallogeneic SBTx in the rat, we prepared three experimental groups. Recipients in group 1 received LBNF1-LBNF1 transplants and were treated with aminoguanidine (AG) (200 mg/kg), recipients in group 2 received Lewis-LBNF1 grafts and were injected with saline, and recipients in group 3 received Lewis-LBNF1 transplants and AG (200 mg/kg). Urine nitrite/nitrate levels were measured daily, and BT was determined by culturing peritoneal swabs, mesenteric lymph nodes, spleen, liver, and blood. RESULTS: In group 1 we detected indefinite survival with normal histology. In group 2 a survival of 10.5 +/- 1.1 days was reached, and the typical histological features of acute GVHD were observed. The animals in group 3 showed a mean survival of 14.8 +/- 0.6 days (P<0.02 compared with group 2) and the histological features of acute GVHD, although with a prolonged time course. Comparing NO production and BT between groups 2 and 3 we detected significantly reduced NO production on postoperative days 2-9 (P<0.03) and significantly decreased BT on postoperative days 3 and 9 (P<0.03). CONCLUSION: Inhibition of inducible NO synthesis with AG reduces NO production, decreases BT, and prolongs survival during GVHD after SBTx and therefore may be a useful addition to standard treatment protocols for GVHD.[Abstract] [Full Text] [Related] [New Search]