Abstract 2074 Pulmonary: General Lung Biology Poster Symposium, Sunday, 5/2

Introduction: Children with congenital heart disease and increased pulmonary blood flow are known to have decreased lung compliance and recurrent pulmonary infections. The etiology of these pulmonary aberrations remains unknown. Recent studies show that increased pulmonary blood flow and/or vascular pressure may influence the alveolar fluid in patients with congenital heart disease. The alveolar fluid is composed of surfactant components which are responsible for lowering the surface tension at the air liquid interface, preventing alveolar collapse at low lung volumes. Deficiencies of surfactant are known to result in decreased lung compliance and respiratory failure. In addition, recent data demonstrate that surfactant plays an important role in pulmonary host defense. Recent in vivo and in vitro data suggest that mechanical forces alter the expression of surfactant in the lung. Increased pulmonary blood flow secondary to congenital heart disease produces increases in vascular shear stress. Alterations in shear stress regulate endothelial function, but their effects on pulmonary alveolar epithelial function have not been investigated. We have recently established a model of pulmonary hypertension secondary to increased pulmonary blood flow in the lamb following in utero placement of an aortopulmonary vascular graft. The purpose of the present study was to utilize our animal model to determine the effect of increased pulmonary blood flow on the expression of surfactant protein A (SP-A).

Methods: An aorto-pulmonary shunt graft was placed in four late-gestation fetal lambs (shunt). Four weeks after delivery, shunted lambs and age-matched control lambs were instrumented to measure vascular pressures and blood flows. In addition, peripheral lung tissue was obtained from shunted and control animals and analyzed for SP-A mRNA by Northern Blot analysis and SP-A protein content by dot blot analysis. Radiolabeled bands were quantitated by phosphorimaging.

Results: At four weeks of age, shunted lambs had a mean pulmonary arterial pressure of 48.3±11.7 mmHg, which represents 78% of systemic values. In addition their pulmonary-to-systemic blood flow ratio was 2.25±1.3 as determined by the Fick equation. Pulmonary hypertension and increased pulmonary blood flow altered gene expression and protein content of SP-A. In shunted lambs SP-A mRNA content was decreased to 61.4% of age-matched control values (n=4, p<.05). In addition, SP-A protein content was decreased to 39.4% of controls (n=4, p<.05).

Conclusions: Increased pulmonary blood flow and/or pressure decreases the gene expression and protein content of surfactant protein A in a lamb model of congenital heart disease. These aberrations in surfactant protein A regulation may play a role in the abnormal lung compliance and increased incidence of pulmonary infections noted in children with increased pulmonary blood flow. The effects of increased pulmonary blood flow and pulmonary hypertension on alveolar epithelial function warrants further study.