Increased nitric oxide levels in exhaled air of rat lung allografts

In organ transplantation nitric oxide has been reported to be involved in allograft rejection. We examined in a rat lung transplantation model whether nitric oxide is overproduced in acute rejection and can be detected in exhaled air. Thirteen rat right lung transplants were separated into three groups: group 1 (n = 5), untreated allografts (Brown-Norway [RT1n] to Lewis [RT1l]); group 2 (n = 4), cyclosporine-treated allografts; and group 3 (n = 4), isografts (Lewis to Lewis). We examined exhaled nitric oxide levels with a chemiluminescence analyzer and chest roentgenograms on days 2 through 5. Histologic samples were obtained on days 3 and 5. On day 5, the recipients were killed and we measured exhaled nitric oxide from the right and left lungs separately. Blood samples were also obtained for measurement of serum nitrite/nitrate. The exhaled nitric oxide level in untreated allografts increased significantly from day 5 (63.9 +/- 39.2 ppb, p = 0.0095) and was significantly higher than that in treated allografts (9.1 +/- 1.6 ppb) (p = 0.0085) and isografts (6.9 +/- 0.5 ppb) (p = 0.0068). The nitric oxide level in untreated allografts (826.5 +/- 416.1 ppb) was 75 times as high as that from the contralateral normal left lungs (11.2 +/- 2.6 ppb) (p = 0.0118). The level of exhaled nitric oxide correlated significantly with the histologic rejection grade (p = 0.0001). There was no significant difference in the serum nitrite/nitrate levels between allografts and isografts. These data suggest that increased exhaled nitric oxide levels might reflect acute rejection in lung transplants.