Chronic effects of pulmonary artery stenosis on hemodynamic and structural development of the lungs

Abstract

Pulmonary artery (PA) stenosis is a difficult obstructive defect to manage since clinicians cannot know a priori which obstructions to treat and when. Prognosis of PA stenosis and its chronic effects on lung development are poorly understood. This study aimed to characterize the hemodynamic and structural effects of PA stenosis during development. Fourteen male Sprague-Dawley rats underwent left PA (LPA) banding at age 21 days, and 13 underwent sham operation. Hemodynamic and structural impacts were studied longitudinally at 20, 36, 52, 100, and 160 days. Chronic LPA banding resulted in a significant reduction in LPA flow (P < 0.0001) and size of both proximal LPA (P < 0.0001) and distal LPA (P < 0.01), as well as a significant increase in flow and size of the right PA (P < 0.05) throughout development. Flows and sizes adapted such that normal levels of wall shear were restored after banding. At 160 days, LPA banding resulted in a significant decrease in left lung volume and an increase in right lung volume but no significant differences in total lung volume. There was an elevation of proximal LPA pressure as well as right ventricular hypertrophy in the banded animals. The banded lung exhibited arterial disorganization, loss of vessels, and enlargement of its bronchial arteries, whereas the contralateral lung showed signs of vascular pathology. There are consequences on development of both lungs in the presence of an LPA stenosis at young age. These results suggest that early intervention may be necessary to optimize left lung growth and minimize right lung vascular pathology.

Pulmonary artery and lung parenchymal growth following early versus delayed stent interventions in a swine pulmonary artery stenosis model

“…In swine, it appears that medial wall thickening in response to PAS occurs over time and that stenting prevents these vascular changes. This increased medial wall thickness is contrary to unilateral PAS studies in neonatal rats 9 where decreased PBF led to smaller PAs in a constant state of vasodilation that histologically manifests as medial atrophy proposed to reduce PVR. Distal to the PAS in the developing rat PBF, PA pressures and pulsatility are reduced leading to abnormal lung development with a reduced number of vessels and a loss of vascular organization, both of which effected alveolar growth.…”

“…Over subsequent years, chronic PAS is associated with PBF mal-distribution that may cause pulmonary artery (PA) hypertension, pulmonary valve insufficiency and increased right ventricular afterload 3,4 all contributing to long term morbidity and mortality. [5][6][7] Given the fact that severely stenotic or occluded branch pulmonary arteries do not grow normally, 8,9 it is assumed that normal pulsatile PBF is essential for lung and PA development and growth. Yet, it is unknown how the pulmonary circulation remodels in response to different durations of hypoperfusion and how much growth and function can be recovered with interventions at differing time periods of lung development.…”

Consequences of an early catheter‐based intervention on pulmonary artery growth and right ventricular myocardial function in a pig model of pulmonary artery stenosis

“…It is intriguing that the LPA immediately distal to the stent did not grow to normal size or increase in diameter between the second and third catheterizations. The lack of compliance of the stented region, or inability of the PA to lengthen, may inhibit growth of the segment immediately distal to the stent . The improvement we observed in the distal first order PA branches after intervention is encouraging for improved long‐term lung growth and function.…”

Recent advances in the mechanisms of lung alveolarization and the pathogenesis of bronchopulmonary dysplasia

“…In an effort to delineate the impact of congenital heart defects on lung development, Razavi and coworkers (296) Increased vascular remodeling and decreased angiogenesis employed a model of pulmonary artery stenosis in rats. After the left pulmonary artery was banded at 21 days of life, lung structure was assessed at 160 days.…”