The area of research has been the sequence of changes in lung volumes and deflation stability during the first several days of life in premature monkeys with hyaline membrane disease (HMD). The candidate now seeks to expand his training in lung morphology and morphometry in order to provide a structural explanation for the observed changes in lung volume in animals with HMD. The research plan is designed to investigate the mechanisms for the fall in total lung capacity (TLC) during the development of HMD and for the increases observed during recovery. Preliminary experiments suggest that the fall in TLC may be due in part to atelectasis, but that other causes may be equally important. It is speculated that a better understanding of these other mechanisms, and the resolution of them during recovery, may provide important information about the abnormal repair processes that lead to bronchopulmonary dysplasia. The research plan proposes to measure TLC in prematurely delivered Macaca nemestrina monkeys with HMD and in controls. Animals will then be selected for sacrifice at three crucial states in the pathophysiology of HMD: as TLC is falling, after it has reached its nadir, and after return to normal. The inflated lung will then be quick frozen in situ, freeze dried, and examined by standard morphometric techniques. It is predicted that TLC will fall because of the development of airway debris and lung edema in addition to atelectasis; persistence of a decreased TLC may be caused, in part, by proliferation of type II pneumocytes. Research will be conducted within the research training environment of the Pediatric Pummonary Training Center and within the facilities of the Primate Center and the Perinatal Biology Laboratories at the University of Washington. Faculty with expertise in the pathophysiology of HMD, lung morphology and morphometry, and lung mechanics will supervise the research.
