Pentoxifylline Reduces Regional Inflammatory and Ventilatory Disturbances in Meconium-Exposed Piglet Lungs

Abstract

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 Ͻ2 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-␣ (TNF-␣) 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-␣ 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-␣ production as well as alveolocapillary permeability rather than via significant prevention of accumulation of active neutrophils in the insulted lungs. Perinatal aspiration of meconium frequently produces respiratory failure with hypoxemia, hypercapnia, and acidosis in the newborn infant and may be complicated by air leaks, pulmonary hypertension, hypoxic organ damage, and long-term pulmonary sequelae (1,2). The pathophysiology of the meconium aspiration syndrome (MAS) is complex and includes initial mechanical obstruction of the airways, ventilation/perfusion mismatch, surfactant inactivation, and progressively developing inflammatory lung injury (1-6). Aspirated meconium may directly damage the alveolar-capillary membrane and may also augment pulmonary injury through activation of alveolar macrophages, inflammatory cytokine production, and accumulation of polymorphonuclear neutrophils (PMNs) (1,2,6,7). Whereas the uneven distribution of inhaled meconium leads to localized areas of injury with variable aeration of the affected lungs, the contribution and mechanisms of the patchy inflammatory processes to the pulmonary dysfunction induced by meconium aspiration is still unclear. Consequently, the therapeutic value of anti-inflammatory agents in the management of MAS remains controversial (6,8 -12).Pentoxifylline (PTX), a methylxanthine derivative and phosphodiesterase inhibitor, has hemorheol...

Effects of hypothermia on lung inflammation in a rat model of meconium aspiration syndrome

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Pentoxifylline and prevention of hyperoxia-induced lung ­injury in neonatal rats

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The role of complement in meconium aspiration syndrome

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