Thorac Cardiovasc Surg 1997; 45(2): 78-82
DOI: 10.1055/s-2007-1013692
Original

© Georg Thieme Verlag Stuttgart · New York

Inhibition of Inducible Nitric Oxide Synthase Prolongs Rat Lung Allograft Survival

T. Shiraishi, B. Chen, K. Okabayashi, S. Yoneda, K. Ando, A. Iwasaki, K. Kawahara, T. Shirakusa
  • Second Department of Surgery, Fukuoka University School of Mediane, Fukuoka City, Fukuoka, Japan
Further Information

Publication History

1996

Publication Date:
19 March 2008 (online)

Abstract

Nitric oxide (NO) has been demonstrated to be an important immunoregulation molecule in the process of cellular immunologic interactions. Our recent results demonstrated that NO is produced in association with acute allograft rejection and NO inhibition may suppress rejection histologically. This data provides direct evidence of NO in allograft rejection and the immunosuppressive potential of NO inhibitors. In this paper, the effect of NO inhibition on allograft survival was evaluated to investigate the capacity of NO inhibitors as immunosuppressive agents. Seventeen rat left lung transplants from BN donors to F344 recipients were accepted for this study. After surgery, recipients were randomized into two groups and received either aminoguanidine (AG), a highly selective NO synthase inhibitor, 200 mg/kg, intraperitoneal every 6 h (n = 13) or normal saline treatment (n = 4). NO production was determined from the recipient's serum nitrite and nitrate levels. Graft survival was monitored via semiquantitative radiographic aeration scores (AS: 0 = opaque lung to 6 = normal appearing lung). The nitrite and nitrate levels were clearly detectable before the radiographic finding associated with rejection became obvious. Production of NO was signifi-cantly inhibited by AG treatment. AG treatment prolonged allograft survival radiographically (12.0 days and 6.0 days for treated and untreated groups respectively, p = 0.0001). These data suggest that the inducible NO is produced in asociation with acute lung allograft rejection and may serve as a sensitive rejection marker. NO inhibition significantly prolonged rat lung allograft survival but failed to induce immunological tolerance.

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