Cytoprotective effects of nitroglycerin in ischemia-reperfusion-induced lung injury

Prevention of ischemia-reperfusion (IR) injury is crucial for successful lu ng transplantation. We investigated whether a nitric oxide donor, nitroglyc erin (NTG), could suppress the oxidative stress of IR injury and improve pu lmonary function after reperfusion in an ex vivo rat lung perfusion model. In Fresh group of animals, the lungs were flushed with perfusate, followed immediately by reperfusion, and no lung injury was observed. In NTG- and NT G+ groups of animals, the lungs were flushed with perfusate alone or perfus ate containing NTG, respectively. Harvested lung and heart blocks from thes e latter two groups were immersed in the corresponding perfusate at 4 degre es C for 15 h, and were then reperfused for 60 min. Reperfusion induced pul monary edema in the NTG- group, but not in the NTG+ group. Shunt fractions in NTG+ group were significantly lower than in the NTG- group throughout re perfusion. NTC had no effect on pulmonary arterial pressure or myeloperoxid ase activity. In contrast, oxidative DNA damage assessed immunohistochemica lly with a monoclonal antibody against 8-hydroxy-2'-deoxyguanosine (8-OHdG) was significantly increased in the NTG- group, in the order alveolar epith elium > pulmonary endothelium > bronchial epithelium. NTG treatment signifi cantly decreased staining with the anti-8-OHdG antibody in all three areas of tissue. Therefore, administration of NTG attenuates the oxidative stress of IR injury, and may improve pulmonary function after reperfusion.