THE EFFECTS OF ADMINISTRATION OF NITRIC-OXIDE INHIBITORS DURING SMALL-BOWEL PRESERVATION AND REPERFUSION

The effects of nitric oxide (NO) during small bowel preservation and r eperfusion were studied in a rat model of heterotopic, syngeneic LEW - -> LEW transplantation. A 6-hr preservation interval was chosen, which leads consistently to moderate graft injury permitting graft and reci pient survival. To evaluate the function of NO during preservation and reperfusion, two inhibitors (Nitro(G)-L-arginine methyl ester [L-NAME ] and N-G-monomethyl-L-arginine [NMA]) were administered and compared with a transplanted group receiving no treatment. The extent of preser vation and reperfusion injury were delineated by histologic study and by the measurement of mucosal glutaminase on tissue specimens obtained 20 min after revascularization and 24 hr and 4 weeks postoperatively. Serum and mucosal NO2-+NO3- levels were determined at the same time p oints. Graft function and survival was inferior in all cases where NO production was inhibited. When recipients were treated with NO inhibit ors, graft function and survival was more impaired when L-NAME was adm inistered compared with NMA administration. Donor and graft pretreatme nt with NO inhibitors impaired graft function but not survival, and wa s less detrimental than recipient treatment. Mucosal NO2-+NO3- levels significantly increased in untreated transplanted animals 20 min after reperfusion. This increase was abolished in groups treated with NO in hibitors. Serum NO2-+NO3- levels increased significantly after 24 hr, and this increase was even more pronounced when NO inhibitors were adm inistered. Furthermore, liver function deteriorated after inhibition o f NO, indicating a more severe inflammatory response of the recipient after NO inhibition. These data indicate that mucosal NO production wi thin the graft during preservation, and especially during reperfusion, has beneficial effects, but increased serum NO2-+NO3- levels coincide d with inferior graft condition due to preservation and reperfusion in jury.