INHALED NITRIC-OXIDE DOES NOT INCREASE RAT PULMONARY ALLOGRAFT-REJECTION

Background: There is evidence that inducible nitric oxide (NO) may be directly related to the process of allograft rejection. Because of its strong pulmonary vasodilatory activity, inhaled NO (INO) has recently been used as a therapeutic option for allograft dysfunction after lun g transplantation. The action of inducible NO and inhaled NO seems con tradictory for preserving posttransplantation pulmonary allograft func tion. INO used for lung transplant recipients may actually enhance acu te allograft rejection. We studied the effect of INO on acute allograf t rejection with a rat pulmonary allograft model. Method: A total of 2 4 left lung allotransplantations were performed from Lewis donors into F344 recipients. Animals were divided into two groups and inhaled eit her room air alone or 20 ppm NO with room air in a closed chamber imme diately after transplantation until rats were killed on days 7 and 14. During observation, NO uptake was monitored by measuring serum NO2-/N O3- level. Acute rejection was evaluated by use of a semiquantitative radiographic scoring method (aeration score: 0 to 6, opaque to normal appearance) and rejection score (0 to 4, no sign of rejection to diffu se mononuclear infiltration). Results: Markedly elevated serum NO2-/NO 3- levels were observed in the NO inhalation group compared with level s in the normal air inhalation control group (110.8 +/- 25.3 vs 16.3 /- 4.0 mu moI/L/ml on day 7, p < 0.01; 107.0 +/- 30.9 vs 16.8 +/- 4.8 mu mol/L/ml. on day 14, p < 0.01). However, no positive effect of INO on acute rejection was found histologically or radiographically. Concl usion: The effect of INO on acute rejection is likely so minimal as no t to be clinically relevant.