EFFECT OF PNEUMONECTOMY AND EXERCISE ON LUNG GROWTH

我们的目标是确定成熟肺的适应潜力

Our objective is to define the adaptive potential of the maturing lung after extensive lung resection (i.e. pneumonectomy) using an integrated structure-function approach. Two mechanisms of compensation are available to the remaining lung after pneumonectomy: 1) greater utilization of existing physiologic reserves (recruitment), and 2) growth of new lung. Our specific aims are to define the limits and functional significance of each mechanism in the overall functional compensation. Answers to these questions are important in understanding the limits of adaptation in the maturing lung; they have broad basic physiological and clinical significance in the optimal management of patients undergoing lung resections. Sixteen litter and sex matched puppies (2 months of age) will be entered into 2 groups. Half the dogs will undergo right pneumonectomy. The other half will undergo sham pneumonectomy. They will be raised simultaneously until full grown (14 months of age) and will be kept exercise trained after surgery until sacrifice. Rates of functional compensation will be assessed during maturation by serial measurements of lung diffusing capacity and its components, maximal O2 consumption, lung volume, pressure-volume relationships and work of breathing at rest and at different workloads up to maximal exercise. After reaching maturity, the ultimate extent of compensation will be assessed by similar measurements plus studies of hemodynamics and gas exchange during heavy exercise. After obtaining physiologic data at maturity, the animals are sacrificed and the lungs fixed in situ for detailed morphometric analysis. The extent of physiologic recruitment is assessed by comparison of results between groups at the same workload. A systematic approach is used to interpret physiologic diffusing capacities as functions of changes in pulmonary blood flow and lung volume. Results are correlated with diffusing capacities calculated from morphometric data in the same animal. The extent and sources of lung growth after pneumonectomy will be assessed by morphometric measurements of alveolar surface area, volume densities of components of the alveoli and number of each type of cells.