DISPARATE EFFECTS OF NITRIC-OXIDE ON LUNG ISCHEMIA-REPERFUSION INJURY

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 und erwent thoracotomy, with clamps used to create left lung ischemia. Aft er 90 minutes of ischemia, clamps were released, permitting reperfusio n for either 30 minutes or 4 hours. Additional animals received inhale d . NO via the ventilator to determine its effects on reperfusion inju ry. Results. Lung injury, measured by increased vascular permeability using iodine-125-labeled bovine serum albumin leakage, was significant ly 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 hou rs. 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 wa s significantly reduced at 4 hours in . NO-treated animals. Conclusion s. . NO is toxic early in reperfusion, due to its interaction with sup eroxide, but is protective at 4 hours of reperfusion, due to reversal of postischemic lung hypoperfusion and reduction of lung neutrophil se questration.