Neonatal chronic lung disease in extremely immature baboons.
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.
Coalson
J J
JJ
Department of Pathology, University of Texas Health Science Center-San Antonio, San Antonio, USA. Coalson@uthscsa.edu
Winter
V T
VT
Siler-Khodr
T
T
Yoder
B A
BA
D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D002452:Cell Count; D004195:Disease Models, Animal; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007378:Interleukins / Q000032:analysis; D008168:Lung / Q000378:metabolism / Q000473:pathology; D010215:Papio; D012121:Respiration, Artificial; D014132:Trachea / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha