PENTOXIFYLLINE DOES NOT PROTECT AGAINST HYPEROXIC LUNG INJURY IN RATS

Hyperoxia has been used extensively as a model of acute lung injury. T he drug pentoxifylline has been shown to have a protective effect in o ther models of lung injury. We sought to determine whether pentoxifyll ine protects against hyperoxic lung injury in rats by decreasing the a ccumulation of neutrophils within the lung. A total of 84 rats were st udied. Twenty four rats were randomized into four groups. Two groups o f rats were pretreated for 48 h with either pentoxifylline (20 mg.kg(- 1)) or saline, and then exposed to >95% O-2 for 60 h while treatments continued. Two groups of control rats received the same treatment regi mens as the O-2-exposed animals, but breathed room air. Neutrophil acc umulation in the lung was quantified both by histology and myeloperoxi dase activity. Lung neutrophil accumulation increased in the oxygen-ex posed group receiving pentoxifylline as compared to oxygen- or air-exp osed rats receiving saline injections. Total glutathione was higher in lung homogenates from the hyperoxic, pentoxifylline-treated group tha n in homogenates from the other three groups. To study survival, 60 ra ts were exposed to >95% O-2 for 120 h, 30 rats were pretreated with pe ntoxifylline, and 30 received saline. Survival after 120 h of exposure to hyperoxia was not altered by pentoxifylline treatment (pentoxifyll ine treated: 6 out of 30 survived; saline treated: 2 out of 30 survive d). We conclude that pentoxifylline does not reduce mortality or lung injury in rats exposed to hyperoxia and is associated with an increase in lung neutrophil accumulation.