Pentoxifylline reduces regional inflammatory and ventilatory disturbances in meconium-exposed piglet lungs

Neonatal meconium aspiration frequently produces severe respiratory distress, which is associated with patchy pulmonary neutrophil influx and inflammatory injury. To examine the effects of pentoxifylline (PTX), a potent anti-inflammatory agent, on regional pulmonary inflammation and ventilation after meconium aspiration, we studied 17 anesthetized and ventilated neonatal piglets (age <2 d) for 12 h. After unilateral intrapulmonary instillation of meconium, PTX treatment was started in nine animals, and eight untreated animals served as controls. Bronchoalveolar lavage (BAL) fluid and lung tissue were studied for inflammatory variables at the end of the study, and changes in regional ventilation were serially analyzed with a dynamic pulmonary x-ray imaging method. Meconium insufflation increased BAL fluid total cell, neutrophil, and macrophage counts and tumor necrosis factor-alpha (TNF-alpha) and protein concentrations as well as lung tissue myeloperoxidase activity in the instilled lungs, compared with the noninstilled side. PTX treatment prevented the increase of BAL fluid alveolar macrophage count and TNF-alpha and protein concentrations in the meconium-instilled lungs but had no significant effect on the pulmonary neutrophil accumulation. Ventilation of the meconium-insulted lung was initially disturbed similarly in both study groups, but PTX administration prevented the sustained local ventilatory perturbation at 4, 6, and 12 h after meconium instillation. The results thus indicate that PTX treatment may attenuate meconium-induced regional ventilation derangements, mainly through its effects on local alveolar macrophages and TNF-alpha production as well as alveolocapillary permeability rather than via significant prevention of accumulation of active neutrophils in the insulted lungs.