Background: Inhaled nitric oxide (.NO) has been found to be a potent pulmonary vasodilator. We assessed whether .NO, through this function or others, could alleviate lung reperfusion injury.
Methods: Rats underwent thoracotomy, with clamps used to create left lung ischemia. After 90 minutes of ischemia, clamps were released, permitting reperfusion for either 30 minutes or 4 hours. Additional animals received inhaled .NO via the ventilator to determine its effects on reperfusion injury.
Results: Lung injury, measured by increased vascular permeability using iodine-125-labeled bovine serum albumin leakage, was significantly increased in ischemic-reperfused animals compared with time-matched shams not undergoing ischemia. Inhaled .NO delivered at the start of reperfusion worsened injury at 30 minutes but was protective at 4 hours. The increased injury could be avoided either by delaying .NO for 10 minutes or by treating the animals with superoxide dismutase before reperfusion. .NO reversed postischemic pulmonary hypoperfusion at 4 hours, as measured by labeled microspheres. Lung neutrophil content was significantly reduced at 4 hours in .NO-treated animals.
Conclusions: .NO is toxic early in reperfusion, due to its interaction with superoxide, but is protective at 4 hours of reperfusion, due to reversal of postischemic lung hypoperfusion and reduction of lung neutrophil sequestration.