Introduction:
Plostagrandin E
1
(PGE
1
) is essential for maintaining the ductus arteriosus (DA) in ductal-dependent congenital heart disease. Recently, relatively long-term administration of PGE
1
became common, especially in patient with hypoplastic left heart syndrome (HLHS) . Staged Norwood approach which consists of bilateral pulmonary artery banding, PGE
1
infusion, and Norwood procedure beyond newborn period provided excellent survival benefit. However, microstructural changes of DA after long-term PGE
1
administration remain unknown. Therefore, we sought to investigate their features of DA after long-term PGE
1
administration using synchrotron based X-ray phase-contrast tomography (XPCT), a novel modality to inspect biological soft tissue, and pathological scrutiny including DA specific immunostaining.
Methods:
Seventeen DA tissues of HLHS were obtained during Norwood procedure. The median duration of PGE
1
was 48 days (Range 3-123). Radiographic microstructural analysis of DA was performed using X-ray phase contrast tomography at SPring-8 (Hyogo, Japan). Histological changes focused on elastic fiber and smooth muscle formation were evaluated by Elastica van Gieson staining, and expression of prostaglandin E2 receptor EP4 was evaluated by immunohistochemical analysis.
Results:
XPCT study showed a sclerotic changes of ductal media. There was a significant correlation between the duration of PGE
1
infusion and the mass density of ductal media (R: 0.723, p=0.001). Histological study showed that the duration of PGE1 infusion was positively correlated with the elastic fiber formation (R: 0.795, P=0.002), and negatively correlated with smooth muscle formation (R: -0.83, P<0.001). The EP4 expression was disappeared in all DA.
Conclusion:
Long-term administration of PGE
1
induced elastogenesis and density growth of the ductal media. In addition, downregulation of EP4 was observed. These results suggested that dosage of PGE
1
could be decreased after definite period of administration.
The Effect of Long-term Administration of Prostaglandin E1 on Morphological Changes in Ductus Arteriosus