Lung hypoplasia and persistent pulmonary hypertension are the principal causes of high mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Amine-and peptide-producing pulmonary neuroendocrine cells (PNEC), widely distributed throughout the airway mucosa, are thought to play an important role in both pulmonary development and regulation of pulmonary vascular tone. Furthermore, recent studies show increased levels of calcitonin gene-related peptide (CGRP), a pulmonary vasodilator produced by PNEC, during chronic hypoxia. The article reports data on morphometric analysis of CGRP immunoreactive PNEC clusters (neuroepithelial bodies, NEB) in a rat model of CDH. CDH was induced in neonatal Sprague Dawley rats by oral administration of 2,4-dichloro-phenyl-p-nitrophenylether (Nitrofen; Rohm Haas, Philadelphia, PA) to the mother at 10 days of gestation. Sections of lungs from term neonatal rats with and without CDH and controls were immunostained for CGRP (marker of NEB) with specific antibody against rat CGRP. NEB size and number of NEB/area of lung were assessed using a semiautomatic image analysis system. In lungs of neonatal rats with CDH, the number of NEB per surface area of lung parenchyma was significantly increased compared with the age-matched controls. Although the mean size of NEB was larger in CDH, the differences were not significant. This is the first study of PNEC in CDH. Whether the phenomenon observed in this study results in altered NEB function including imbalance in vasoactive mediators requires further studies, especially in the human being.
Bibliographical noteFunding Information:
From the Department of Pediatric Surgery and the Department of Pediatrics, Division of Respiratory Medicine, Erasmus University and University Hospital~Sophia Children's Hospital, Rotterdam, The Netherlands, and the Department of Pathology and The Research Institute, MRC Lung Development Group, The Hospital for Sick Children, and the University of Toronto, Toronto, Ontario, Canada. Presented at the 41st Annual International Congress of the British Association of Paediatric Surgeons, Rotterdam, The Netherlands, June 29-July 1, 1994. Supported by the Netherlands Asthma Foundation, project no. 91.56, and a Medical Research Council of Canada Lung Development Group grant. Address reprint requests to Professor Dr D. Tibboel, Department of Pediatric Surgery, Sophia Children's Hospital, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. Copyright © 1995 by W.B. Saunders Company 0022-3468/95/3003-0009503. O0/ 0