Effect of amniotic fluid and meconium in the lung of neonatal Fischer 344 rats

Meconium aspiration syndrome (MAS) is a major contributor to neonatal respiratory distress and an important cause of morbidity and mortality in infants. This syndrome has been recognized in foals, calves and puppies and pulmonary lesions in these animals are similar to those described in babies with MAS. There are few reliable animal models to evaluate the lesions and inflammatory response associated with MAS under laboratory conditions. The objectives of this investigation were: (1) to standardize a murine model of MAS using intratracheal inoculation (ITI) in 7-day-old rats. (2) to quantify the cytological and biochemical changes in the bronchoalveolar lavage (BAL) after ITI of amniotic fluid and meconium. (3) to evaluate and quantify the microscopic and ultrastructural changes in the lungs after ITI of meconium.

Results of this investigation showed that pulmonary alveolar macrophages (PAM) are present in the fetal lung and the numbers increase significantly during the first 3 days of life. After 3 days, the cell counts are comparable to young or adult rats. During the postnatal period, there is a transient influx of neutrophils (PMN) into the bronchoalveolar space. The lungs of normal rat neonates have high activities of alkaline phosphatase (ALP) and lactate dehydrogenase, and gamma-glutamyltransferase (GGT) and protein increase transiently during the first few days of life.

20% unfiltered homologous meconium induced a sharp increase in PMN shortly after inoculation. Meconium also induced a significant influx of PAM, vascular sequestration of PMN and aggregation of platelets in capillaries. Meconium caused a transient injury to the cells of the respiratory membrane characterized by a significant increase of enzymatic activity. Ultrastructurally, cell injury was moderate and transient and did not lead to extensive necrosis of epithelial cells. Protein leakage suggesting an alteration of vascular permeability was also detected in the neonates inoculated with meconium. Other meconium-associated changes included atelectasis and hyperinflation and a significant thickening of alveolar septa. Ultrastructurally, alveolar thickening coincided with interstitial edema and sequestration of PMN. The early neutrophilic response progressed into a persistent multifocal histiocytic and granulomatous reaction and some granulomatous foci eventually calcified or became lined by cuboidal cells. There were moderate hypertrophy and hyperplasia of type II pneumocytes, mild interstitial proliferation of mesenchymal cells and focal intraalveolar fibrosis. Topographically, the centriacinar region and neighboring alveoli were the main sites affected by meconium. (Abstract shortened by UMI.).