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

Abstract

Objectives: Compare lung parenchymal and pulmonary artery (PA) growth and hemodynamics following early and delayed PA stent interventions for treatment of unilateral branch PA stenosis (PAS) in swine.

Background: How the pulmonary circulation remodels in response to different durations of hypoperfusion and how much growth and function can be recovered with catheter directed interventions at differing time periods of lung development is not understood.

Methods: A total of 18 swine were assigned to four groups: Sham (n = 4), untreated left PAS (LPAS) (n = 4), early intervention (EI) (n = 5), and delayed intervention (DI) (n = 5). EI had left pulmonary artery (LPA) stenting at 5 weeks (6 kg) with redilation at 10 weeks. DI had stenting at 10 weeks. All underwent right heart catheterization, computed tomography, magnetic resonance imaging, and histology at 20 weeks (55 kg).

Results: EI decreased the extent of histologic changes in the left lung as DI had marked alveolar septal and bronchovascular abnormalities (p = .05 and p < .05 vs. sham) that were less prevalent in EI. EI also increased left lung volumes and alveolar counts compared to DI. EI and DI equally restored LPA pulsatility, R heart pressures, and distal LPA growth. EI and DI improved, but did not normalize LPA stenosis diameter (LPA/DAo ratio: Sham 1.27 ± 0.11 mm/mm, DI 0.88 ± 0.10 mm/mm, EI 1.01 ± 0.09 mm/mm) and pulmonary blood flow distributions (LPA-flow%: Sham 52 ± 5%, LPAS 7 ± 2%, DI 44 ± 3%, EI 40 ± 2%).

Conclusion: In this surgically created PAS model, EI was associated with improved lung parenchymal development compared to DI. Longer durations of L lung hypoperfusion did not detrimentally affect PA growth and R heart hemodynamics. Functional and anatomical discrepancies persist despite successful stent interventions that warrant additional investigation.

Keywords: congenital heart disease; pediatric interventions; pulmonary artery stenting.

Figure A1:

A. Measurement of RPA, LPA and 1^st order branch PA diameters were made at 6 consistently identified right side 1^st order branches and 5 consistently identified left side 1^st order branches. B-C. RPA/LPA diameters were measured adjacent to the first order branch and the 1^st order branch diameters were measured at the branch artery origins.

Figure A2:

Main RPA diameter and RPA 1^st order branch diameters were not different between groups.

Figure A3:

Proximal LPA, main LPA, LPA 1^st order branch, main RPA, RPA 1^st order branch diameters in mm (i.e. not indexed to Ao diameter). * p<0.05 vs sham, ^#p<0.05 vs LPAS

Figure 1:

Study timeline

Figure 2:

Response of HR and RV systolic pressure to 5mcg/kg/min dobutamine infusion. Sham (n=4), LPAS (n=4), DI (n=4), EI (n=4).

Figure 3:

3D reconstructions of PA anatomy, proximal LPA diameter, main LPA diameters and LPA 1^st order branch diameters. Sham (n=4), LPAS (n=4), DI (n=5) and EI (n=5). * p<0.05 vs sham control, ^# p<0.05 vs LPAS control

Figure 4:

3D reconstructions of the right and left lung volumes from CT and the left lung volume ratios for sham (n=4), LPAS (n=4), DI (n=5) and EI (n=5). * p<0.05 vs sham control, ^# p<0.05 vs LPAS control

Figure 5:

Representative left lung bronchiole with associated pulmonary arteriole for (A) sham, (B) LPA stenosis control demonstrating increased bronchiolar arterioles (black arrows) and a small pulmonary arteriole with significant medial hypertrophy (white arrow) and (C) EI, demonstrating relatively normal bronchiolar arteries with normal appearing pulmonary arterioles.