Related Experiment Videos
Neonatal chronic lung disease in extremely immature baboons
J J Coalson1, V T Winter, T Siler-Khodr
1Department of Pathology, University of Texas Health Science Center-San Antonio, San Antonio, USA. Coalson@uthscsa.edu
Insights
A new baboon model for bronchopulmonary dysplasia (BPD) shows impaired lung development and inflammation in premature infants, even with careful ventilation. This research offers insights into chronic lung disease of infancy (CLD) in extremely premature babies.
Area of Science:
- Neonatal Physiology
- Pulmonary Medicine
- Animal Models
Background:
- Bronchopulmonary dysplasia (BPD)/chronic lung disease of infancy (CLD) significantly impacts extremely premature infants.
- Existing models do not fully replicate the complex pathophysiology observed in human neonates.
Purpose of the Study:
- To describe a borderline viability model of BPD/CLD in premature baboons.
- To characterize the pulmonary pathophysiology in this model, mirroring extremely immature human infants.
Main Methods:
- Prenatal steroid treatment followed by cesarean delivery at 125 days gestation (term 185 days).
- Postnatal management included surfactant, controlled oxygen, and positive pressure ventilation for 1-2 months.
- Histopathological analysis, lung function measurements, and inflammatory cytokine assessment (TNF-alpha, IL-6, IL-8) were performed.
Main Results:
- The baboon model exhibited alveolar hypoplasia, saccular wall fibrosis, and reduced internal surface area, consistent with human BPD/CLD.
- Decreased capillary vasculature and dysmorphic changes were observed.
- Elevated TNF-alpha, IL-6, and IL-8 levels in tracheal aspirates indicated mediator-induced autoinflammation.
Conclusions:
- This baboon model effectively replicates key features of BPD/CLD in extremely premature infants.
- Impaired alveolization and capillary development occur even with optimized oxygen and ventilation.
- The model supports a role for inflammatory mediators in the pathogenesis of BPD/CLD.
Abstract:
A borderline viability model of bronchopulmonary dysplasia (BPD)/chronic lung disease of infancy (CLD) with pathophysiologic parameters consistent with those in extremely immature humans with BPD/CLD is described. After prenatal steroid treatment of pregnant dams, 12 premature baboons were delivered by cesarean-section at 125 d (term gestation, 185 d), treated with exogenous surfactant, and maintained on appropriate oxygen and positive pressure ventilation for at least 1 to 2 mo. In spite of appropriate oxygenation (median FI(O(2)) at 28 d = 0.32; range, 0.21 to 0.50) and ventilatory strategies to prevent volutrauma, the baboons exhibited pulmonary pathologic lesions known to occur in extremely immature humans of less than 1,000 g: alveolar hypoplasia, variable saccular wall fibrosis, and minimal, if any, airway disease. The CLD baboon lungs showed significantly decreased alveolization and internal surface area measurements when compared with term and term + 2-mo air-breathing controls. A decrease in capillary vasculature was evident by PECAM staining, accompanied by dysmorphic changes. Significant elevations of TNF-alpha, IL-6, IL-8 levels, but not of IL-1beta and IL-10, in tracheal aspirate fluids were present at various times during the period of ventilatory support, supporting a role for mediator-induced autoinflammation. IL-8 levels were elevated in necropsy lavages of animals with significant lung infection. This model demonstrates that impaired alveolization and capillary development occur in immature lungs, even in the absence of marked hyperoxia and high ventilation settings.