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Attempts to attenuate lung reperfusion injury by administration of inhaled nitric oxide have yielded conflicting results. We hypothesized that the inspired oxygen fraction may play an important role in determining the outcome of nitric oxide therapy.Rat lungs were reperfused in a circuit incorporating a support animal either immediately after flushing (group A) or after 24-hr hypothermic storage (groups B-D). During the first 10 min of reperfusion, grafts were ventilated with 95% oxygen in groups A and B, 95% oxygen and 20 ppm nitric oxide in group C, and 20% oxygen and 20 ppm nitric oxide in group D. Ventilation during the subsequent 50 min of reperfusion was with 100% oxygen only, in all groups.Graft function in group B was poor compared to group A in terms of blood flow and pulmonary artery and peak airway pressures. In group C, although 5 out of 10 grafts functioned at control levels, the remainder performed poorly. Function in group D, on the other hand, was uniformly good.Inhaled nitric oxide can prevent lung reperfusion injury, but this effect may be compromised by concurrent ventilation with high oxygen concentrations.