The effect of pentoxifylline on the pulmonary response to high tidal volume ventilation in rats

Background: Volume-induced lung injury is associated with lung inflammation. Pentoxifylline inhibits cytokine release and modulates neutrophil function. Objective: To evaluate the efficacy of pentoxifylline in the attenuation of lung inflammation induced by high tidal volume ventilation. Design: Adult rats were randomly assigned to receive saline as placebo or pentoxifylline (100 mg/kg over 30 min, followed by 50 mg/kg/h) before and during 4 h of high tidal volume ventilation (20 ml/kg). Bronchoalveolar fluid inflammatory mediators were measured at baseline and after 4 h of ventilation. Lung tissue myeloperoxidase activity and wet/dry lung weight were assessed upon completion of the study. Results: Bronchoalveolar tumor necrosis factor-α (pentoxifylline vs. placebo; 192±61 vs. 543±99 pg/ml; p < 0.007) and thromboxane B₂ (262±26 vs. 418±49 pg/ml; p < 0.02) concentrations, lung myeloperoxidase activity (0.5±0.1 vs. 1.2±0.2 U/mg; p < 0.003) and wet/dry weight (6.1±0.2 vs. 7.1±0.3; p < 0.01) were all significantly lower in the pentoxifylline-treated group. Conclusion: Pentoxifylline was effective in reducing inflammatory lung injury associated with high tidal volume ventilation.