The objective of this proposed study is to determine the effects of several growth modulators (glucocorticoid- T4, retinol, and bombesin-like peptides (BLP)) on lung growth and development in treated long-term survivors with bronchopulmonary dysplasia (BPD). The hypothesis is that the use of growth modulators will enhance lung maturation, especially alveolarization, in premature baboons with induced BPD. The three specific aims are: 1. To characterize by morphologic and morphometric techniques the effects of premature delivery at decreasing gestations on long-term lung growth parameters, including lung volumes, volume proportions of lung components, numbers of airways and alveoli per unit area of volume. These measurements will be made after 12-14 days of ventilation and after 33 and 35 weeks of survival in prematurely delivered 125 and 140 day gestational age baboons, and compared to vaginally delivered, term baboons allowed to survive to the same postconceptual age (i.e. 27 weeks). 2. To characterize and contrast the effects of induced BPD in the 125 days and 140 day BPD models on the postnatal development of the premature baboon lung, using the time points and measurements described in Specific Aim 1. 3. To characterize the effect of early preventive therapies with optimized regimens of either BLPs, retinol or GC-T on long-term alveolarization, growth, and development of premature animals with and without bronchopulmonary dysplasia using lung growth parameters described in Specific Aim 1 at 12-14 days and 33-35 weeks after the treatments. BPD is a dysregulated lung repair process which may be responsive to the actions of several growth modulators which may either enhance maturation or ameliorate ongoing lung injury. Quantitative assessments of the efficacies of these treatment strategies can only be obtained by morphometric techniques. It is important to ascertain that any short-term benefits of the use of these agents would not be at the cost of adversely affecting the long-term growth and maturation of the lung. The accelerated growth rate of the baboon will allow us to study lung tissues in these injured animals at a time period which is similar to the 2-year-old human in whom lung maturation and especially alveolarization would be complete, i.e., 35 weeks in the 125 d model and 33 weeks in the 140 d model.
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