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Am. J. Respir. Crit. Care Med., Volume 161, Number 3, March 2000, 935-943

Cytoprotective Effects of Nitroglycerin in Ischemia-Reperfusion-Induced Lung Injury

MASAHIRO KAWASHIMA, TORU BANDO, TAKAYUKI NAKAMURA, NORITAKA ISOWA, MINGYAO LIU, SHINYA TOYOKUNI, SHIGEKI HITOMI, and HIROMI WADA

Department of Thoracic Surgery, Faculty of Medicine, and Departments of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan; and Division of Thoracic Surgery, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada

Prevention of ischemia-reperfusion (IR) injury is crucial for successful lung transplantation. We investigated whether a nitric oxide donor, nitroglycerin (NTG), could suppress the oxidative stress of IR injury and improve pulmonary 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 NTG+ groups of animals, the lungs were flushed with perfusate alone or perfusate containing NTG, respectively. Harvested lung and heart blocks from these latter two groups were immersed in the corresponding perfusate at 4° C for 15 h, and were then reperfused for 60 min. Reperfusion induced pulmonary 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 reperfusion. NTG had no effect on pulmonary arterial pressure or myeloperoxidase activity. In contrast, oxidative DNA damage assessed immunohistochemically with a monoclonal antibody against 8-hydroxy-2'-deoxyguanosine (8-OHdG) was significantly increased in the NTG- group, in the order alveolar epithelium > pulmonary endothelium > bronchial epithelium. NTG treatment significantly 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. Kawashima M, Bando T, Nakamura T, Isowa N, Liu M, Toyokuni S, Hitomi S, Wada H. Cytoprotective effects of nitroglycerin in ischemia-reperfusion-induced lung injury.




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