This work will investigate mechanisms of airway growth. Post- pneumonectomy airway growth in the ferret will be used as an experimental model because of the precision with which the lung and airway growth which follows penumonectomy can be studied and the ease with which factors influencing airway growth can be manipulated during the brief response. Airway growth will be assessed with a morphometric technique for quantitating the size of airways at four levels in the bronchial tree based on analysis of bronchial casts. The first Protocol will investigate the role of mechanical forces in airway growth be separating in time the increase in mechanical stretch applied to the airways following pneumonectomy from concomitant changes in perfusion and ventilation and from the stress of surgery: the resected lung will be replaced at surgery with an inert silicone oil which will be removed by needle thoracostomy one week later. The timing and extent of airway and lung growth following the abrupt increase in mechanical stretch due to the removal of the plombage will be compared with that which immediately follows pneumonectomy without plombage. Serial plasma samples will be used to assess changes in levels of somatomedin-C during compensatory lung growth. In Protocol B, this experimental model will be used to assess the influence of physiologic and pharmacologic levels of glucocorticoids on compensatory airway growth by quantitating airway and lung growth and circulating levels of somatomedin-C in cortisol-deficient animals and in animals treated with exogenous glucocorticoids. In Protocol C compensatory airway growth will be assessed in growth hormone-deficient (hypophysectomized) animals. In addition to elucidating mechanisms of airway growth these studies will provide a basis from which to pursue studies of the cellular manifestations of airway growth. In the third year, autoradiography will be used to identify the cellular kinetics of airway growth using models developed in the first two years. Serial plasma samples will be collected and stored for future analyses for peptide growth factors as such factors are specifically identified.
| Wood, J P; Kolassa, J E; McBride, J T (1998) Changes in alveolar septal border lengths with postnatal lung growth. Am J Physiol 275:L1157-63 |
