Obliterative
bronchiolitis (OB) affects over half of all survivors following lung or
heart-lung transplantation. Respiratory epithelial cell injury, peribronchial
inflammation, and proliferation of fibrovascular tissue causing airway occlusion characterize the lesion. While
peroxynitrite is known to participate in other models of
acute lung injury, its role in the evolution of OB is unclear. Using a rat model of experimental OB, tracheas from Brown-Norway or Lewis rats were transplanted into Lewis recipients. Treated animals received FP-15, a
peroxynitrite decomposition catalyst, at 1 mg/kg/day intraperitoneal for 14 days.
Luminal obstruction, epithelial loss, and inflammatory infiltrate were examined, as was
nitrotyrosine staining by immunohistochemistry in explanted tracheas. By postoperative day 14, control allografts demonstrated marked peribronchial
inflammation, near complete loss of respiratory epithelium and extensive intraluminal proliferation of fibrovascular connective tissue, with a mean 83% reduction in airway cross-sectional area. Allograft recipients treated with FP-15 showed reduced
nitrotyrosine formation, preservation of respiratory epithelium, limited peribronchial
inflammation, and only 14% (P <.001) reduction in airway cross-sectional area.
Peroxynitrite therefore appears to play a role in the development of obliterative
bronchiolitis in rats. The
peroxynitrite decomposition catalyst, FP-15, is protective when administered daily and warrants investigation into its potential clinical utility.