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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R10)
Project #
1R10HL052646-01
Application #
3568476
Study Section
Special Emphasis Panel (ZHL1-CCT-G (M1))
Project Start
1994-07-20
Project End
1999-05-31
Budget Start
1994-07-20
Budget End
1995-05-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Yoder, Bradley A; Coalson, Jacqueline J (2014) Animal models of bronchopulmonary dysplasia. The preterm baboon models. Am J Physiol Lung Cell Mol Physiol 307:L970-7
Loeliger, Michelle; Shields, Amy; McCurnin, Donald et al. (2010) Ibuprofen treatment for closure of patent ductus arteriosus is not associated with increased risk of neuropathology. Pediatr Res 68:298-302
Loeliger, Michelle; Inder, Terrie E; Shields, Amy et al. (2009) High-frequency oscillatory ventilation is not associated with increased risk of neuropathology compared with positive pressure ventilation: a preterm primate model. Pediatr Res 66:545-50
Yoder, Bradley A; Coalson, Jacqueline J; Winter, Vicki T et al. (2003) Effects of antenatal colonization with ureaplasma urealyticum on pulmonary disease in the immature baboon. Pediatr Res 54:797-807
Yoder, BradleyA; Martin, Helen; McCurnin, Donald C et al. (2002) Impaired urinary cortisol excretion and early cardiopulmonary dysfunction in immature baboons. Pediatr Res 51:426-32
Awasthi, S; Coalson, J J; Yoder, B A et al. (2001) Deficiencies in lung surfactant proteins A and D are associated with lung infection in very premature neonatal baboons. Am J Respir Crit Care Med 163:389-97
Yoder, B A; Siler-Khodr, T; Winter, V T et al. (2000) High-frequency oscillatory ventilation: effects on lung function, mechanics, and airway cytokines in the immature baboon model for neonatal chronic lung disease. Am J Respir Crit Care Med 162:1867-76
Ofek, I; Crouch, E; Keisari, Y (2000) The role of C-type lectins in the innate immunity against pulmonary pathogens. Adv Exp Med Biol 479:27-36
Coalson, J J; Winter, V T; Siler-Khodr, T et al. (1999) Neonatal chronic lung disease in extremely immature baboons. Am J Respir Crit Care Med 160:1333-46
Coalson, J J; Winter, V; Yang, F (1998) Site specificity of surfactant protein expression in airways of baboons during gestation. Anat Rec 250:300-15

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