Abstract 1180
Poster Session IV, Tuesday, 5/4 (poster 278)
Aspiration of meconium produces inflammatory reaction resulting in necrotic changes in lung tissue. To investigate the mechanisms of the meconium-induced early pulmonary injury, tissue samples from twenty 10-12 day-old piglet lungs, ventilated for 6 hours after meconium instillation, were studied for ultrastructural and apoptotic changes, and phospholipase A2(PLA2) activity. Twelve piglets received an intratracheal bolus (3 ml/kg) of a 20 mg/ml (thin, n=6) or 65 mg/ml (thick, n=6) mixture of human meconium, and control piglets (n=5) received the same amount of intratracheal saline. Three piglet lungs with no aspiration were also studied. In the control groups pulmonary alveoli were open with intact alveolocapillary walls, whereas meconium (thin and thick) administration resulted in marked pneumonitis. In these lungs the amount of apoptotic cells, studied by in situ detection of free DNA 3′-ends, was also increased, especially in the epithelium. Thick meconium instillation additionally resulted in edematous changes in the vascular endothelium and alveolar epithelium, whereas type II pneumocytes were intact. Thick intrapulmonary meconium was further associated with high catalytic activity of PLA2 in lung tissue. This activity proved to be due to human group I (pancreatic) PLA2, introduced in high concentration within the meconium. Our data thus show that aspiration of meconium, especially that of thick consistence, leads to severe inflammatory injury in the respiratory epithelium and vascular endothelium, and is associated with apoptotic cell death in the epithelium, already during the first hours after the insult. The results further suggest that high PLA2 activity, mainly introduced within the meconium, may have an important role in the initiation of these alterations in neonatal lungs.
