Department of Cardiovascular Surgery, Kobe Children's Hospital, Hyogo, Japan.
Department of Cardiovascular Surgery, Kobe Children's Hospital, Hyogo, Japan.
Ann Thorac Surg. 2020 Dec;110(6):2088-2095. doi: 10.1016/j.athoracsur.2020.02.053. Epub 2020 Apr 2.
To improve survival of patients with hypoplastic left heart syndrome, combination therapy with bilateral pulmonary artery banding and prostaglandin E (PGE)-mediated ductal patency was developed as an alternative for high-risk neonates in Japan. However, the effect of long-term PGE administration on ductus arteriosus remains unclear. Synchrotron radiation-based X-ray phase-contrast tomography (XPCT) enables clear visualization of soft tissues at an approximate spatial resolution of 12.5 μm. We aimed to investigate morphologic changes in ductus arteriosus after long-term PGE infusion using XPCT.
Seventeen ductus arteriosus tissue samples from patients with hypoplastic left heart syndrome were obtained during the Norwood procedure. The median duration of lipo-prostaglandin E (lipo-PGE) administration was 48 days (range, 3 to 123). Structural analysis of ductus arteriosus was performed and compared with conventional histologic analysis.
The XPCT was successfully applied to quantitative measurements of ductal media. Significant correlation was found between the duration of lipo-PGE infusion and mass density of ductal media (R = 0.723, P = .001). The duration of lipo-PGE administration was positively correlated with elastic fiber staining (R = 0.799, P < .001) and negatively correlated with smooth muscle formation (R = -0.83, P < .001). No significant increase in intimal cushion formation was found after long-term lipo-PGE administration. Expression of ductus arteriosus dominant PGE-receptor EP4 almost disappeared in specimens when lipo-PGE was administered over 3 days.
Disorganized elastogenesis and little intimal cushion formation after long-term lipo-PGE administration suggest that ductus arteriosus remodeled to the elastic artery phenotype. Because EP4 was downregulated and ductus arteriosus exhibited elastic characteristics, the dosage of lipo-PGE might be decreased after a definite administration period.
为提高左心发育不全综合征患者的生存率，在日本，对于高危新生儿，开发了双侧肺动脉带扎和前列腺素 E（PGE）介导的动脉导管开放联合治疗作为替代方案。然而，长期 PGE 给药对动脉导管的影响尚不清楚。基于同步加速器的 X 射线相衬断层摄影术（XPCT）可在约 12.5μm 的近似空间分辨率下清晰地显示软组织。我们旨在使用 XPCT 研究长期 PGE 输注后动脉导管的形态变化。
在 Norwood 手术期间，从患有左心发育不全综合征的患者中获得了 17 个动脉导管组织样本。脂肪前列腺素 E（lipo-PGE）给药的中位数持续时间为 48 天（范围 3 至 123 天）。对动脉导管进行结构分析，并与常规组织学分析进行比较。
XPCT 成功应用于导管管腔的定量测量。脂肪 PGE 输注时间与管腔介质的质量密度之间存在显著相关性（R=0.723，P=0.001）。脂肪 PGE 给药时间与弹性纤维染色呈正相关（R=0.799，P<0.001），与平滑肌形成呈负相关（R=-0.83，P<0.001）。长期脂肪 PGE 给药后未见内膜垫形成明显增加。当脂肪 PGE 给药超过 3 天时，动脉导管中占主导地位的 PGE 受体 EP4 的表达几乎消失。
长期脂肪 PGE 给药后动脉导管出现结构紊乱的弹性生成和少量内膜垫形成，表明动脉导管重塑为弹性动脉表型。由于 EP4 下调且动脉导管呈现弹性特征，因此在确定给药期后，脂肪 PGE 的剂量可能会减少。
