Understanding the pathobiology in patent ductus arteriosus in prematurity-beyond prostaglandins and oxygen
Understanding the pathobiology in patent ductus arteriosus in prematurity-beyond prostaglandins and oxygen
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DOI：
10.1038/s41390-019-0387-7
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发表时间：
2019-07-01
影响因子：
3.6
通讯作者：
de Boode, Willem P.
中科院分区：
文献类型：
--
作者：
Hundscheid, Tim;van den Broek, Martijn;de Boode, Willem P.
动脉导管（DA）可能是出生后血流动力学转变中最有趣的血管。子宫DA通畅是一种活跃状态，前列腺素E-2 （PGE(2)）和一氧化氮（NO）在其中起重要作用。由于随着妊娠的进展，DA被编程为产后关闭，在早产儿中DA经常保持专利（PDA）。PGE(2)暴露通过诱导离子通道和磷酸二酯酶的基因表达和通过诱导内膜增厚来实现功能性产后闭合。出生后，氧抑制钾并激活钙通道，最终导致细胞内钙浓度升高，从而诱导肌球蛋白轻链磷酸化，从而导致DA血管收缩。由于早产婴儿的离子通道表达较低，与足月新生儿相比，氧诱导的功能性血管收缩减弱。此外，与长期DA相比，早产儿DA对PGE(2)和NO更敏感，从而使平衡倾向于更少的收缩。在这篇综述中，我们解释了子宫内DA通畅和随后的产后功能关闭的生理学。我们将重点关注早产儿PDA的病理生物学以及产前暴露于药物对胎儿和新生儿DA血管张力的（非）预期影响。
The ductus arteriosus (DA) is probably the most intriguing vessel in postnatal hemodynamic transition. DA patency in utero is an active state, in which prostaglandin E-2 (PGE(2)) and nitric monoxide (NO), play an important role. Since the DA gets programmed for postnatal closure as gestation advances, in preterm infants the DA frequently remains patent (PDA). PGE(2) exposure programs functional postnatal closure by inducing gene expression of ion channels and phosphodiesterases and anatomical closure by inducing intimal thickening. Postnatally, oxygen inhibits potassium and activates calcium channels, which ultimately leads to a rise in intracellular calcium concentration consequently inducing phosphorylation of the myosin light chain and thereby vasoconstriction of the DA. Since ion channel expression is lower in preterm infants, oxygen induced functional vasoconstriction is attenuated in comparison with full term newborns. Furthermore, the preterm DA is more sensitive to both PGE(2) and NO compared to the term DA pushing the balance toward less constriction. In this review we explain the physiology of DA patency in utero and subsequent postnatal functional closure. We will focus on the pathobiology of PDA in preterm infants and the (un)intended effect of antenatal exposure to medication on both fetal and neonatal DA vascular tone.