Role of Pentoxifylline in the Prevention of Volume Induced Lung Inflammation

Abstract 1893 Neonatal Pulmonology II: Oxidant and Inflammatory Lung Injury Poster Symposium, Tuesday, 5/4

Increasing evidence suggests that the activation of the inflammatory cascade within the lung, whether triggered by infection, oxygen toxicity or barotrauma, plays an important role in the development of neonatal chronic lung disease. Corticosteroids are frequently used to block this inflammatory process, however, this therapy has been associated with considerable adverse effects. Pentoxifylline (PTX), a methylxanthine, acts as a potent inhibitor of cytokine release and alters neutrophil function without significant side effects. To evaluate the efficacy of PTX in the attenuation of lung inflammation induced by ventilation with large tidal volumes, 17 newborn piglets were anesthetized, tracheotomized, paralyzed, and mechanically ventilated with a constant tidal volume of 50 ml/kg for a period of 8 h. Animals were randomly assigned to a treatment group (n=8) that received PTX (20 mg/kg as a bolus, followed by a continuous infusion of 5 mg/kg/h) before and during exposure to the volume induced lung damage, or a control group (n=9) which received saline. Serum and tracheoalveolar fluid (TAF) thromboxane levels (TXB₂) were obtained before and after administration of PTX or saline and at 2 h intervals thereafter until completion of the 8 h study period. Lung tissue myeloperoxidase (MPO), wet to dry lung weight, and lung inflammation on pathological specimens (using a standardized scoring system) were assessed upon completion of the 8 h study. Results (mean±SD) were analyzed using ANOVA and Chi square. (Table)

Table 1 No caption available

A marked increase in TAF TXB₂, lung edema and neutrophil activity was observed after 8 h of high tidal volume ventilation in the saline treated animals. This inflammatory process appears to be localized within the lung since serum TXB₂ levels did not change in either group. A significant reduction in the pulmonary inflammatory response was observed during large tidal volume ventilation in the animals treated with PTX. These results suggest that PTX may be effective in ameliorating lung inflammation associated with mechanical ventilation in neonates.