Time-Dependent Oxidative Alterations in Plasma and Lung Tissue after Meconium Aspiration in a Rabbit Model

Abstract

Aspirated meconium into a newborn’s airways induces the transcription of pro-oxidative mediators that cooperate in the pathogenesis of inflammatory changes and may negatively affect the commonly used exogenous surfactant therapy. However, inflammation is not treated at present, nor is the time dependence of oxidative damage known. The aim of our study was to describe the time course of oxidative stress marker production during meconium aspiration syndrome (MAS) and its relationship to leukocyte infiltration. New Zealand rabbits were instilled with saline or meconium suspension and ventilated for 5.5 h. Respiratory parameters were recorded and blood samples were taken before meconium application and in time intervals of 15 and 30 min, 1.0, 1.5, 3.5 and 5.5 h after application to evaluate oxidative markers and differential leukocytes count. Meconium aspiration led to a worsening of respiratory parameters and a decrease in leukocytes in the first 15 min. Changes in leukocytes were correlated both with nitrotyrosine (3NT) levels and thiobarbituric acid reactive substance (TBARS) levels, with the latter also related to changes in neutrophil count. The production of 3NT and TBARS increased in 1.5 and 3.5 h, respectively, in different ways, suggesting more than one source of oxidative agents and a potential risk of exogenous surfactant inactivation in a short time. We observed that MAS triggered neutrophil migration to the alveolar space and activation, as shown by the increased expression of pro-inflammatory cytokines and generation of indicators of oxidative damage to proteins and lipids during the time period when iNOS and NO metabolites were released.