This research will contribute to the understanding of basic mechanisms of lung growth and repair by studying compensatory lung growth in the ferret. The overall objective is to investigate the extent to which blood flow and distention regulate the lung and airway growth which follows unilateral pneumonectomy and how this regulation is accomplished on a cellular level. The experimental model for these studies permits blood flow and distention after pneumonectomy to be manipulated independently: blood flow by banding the left lower lobe pulmonary artery so that perfusion to the upper lobe increases after pneumonectomy while that to the lower lobe does not, and lung distention by replacing the resected lung with a balloon which prevents distention of the left lung at the time of surgery. This model will be used to investigate the separate and combined effects of perfusion and distention on tissue growth (changes in lobar DNA, protein, hydroxyproline), cellular proliferation (immunostaining of bromodeoxyuridine incorporation), and architectural remodelling (morphometric measurements of lung volume and airway size). These data will be used to test the hypotheses that, during compensatory growth: 1) perfusion determines tissue growth, 2) distention determines architectural remodelling, and 3) the airways and lung parenchyma respond differently to these two stimuli. The hypothesis that insulin-like growth factors or other proteins play a role in compensatory growth will be tested by evaluating expression of these factors after pneumonectomy with immunohistochemical and molecular biologic (Northern/dot blots, in situ hybridization) techniques. The hypothesis that changes in perfusion and/or distention influence the expression of these factors will be tested: first, by investigating the effects of isolated changes in blood flow and/or distention on the expression of factors involved in compensatory lung growth; and second, by relating levels of these factors (quantitated by microdensitometry/image analysis) to the intensity of changes in blood flow and distention after pneumonectomy.
| 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 |
