Department of Pediatrics, UC Davis School of Medicine, Sacramento, CA, USA.
Department of Hospitalist Medicine, Children's National Health System, Washington DC, USA.
Free Radic Biol Med. 2019 Oct;142:97-106. doi: 10.1016/j.freeradbiomed.2019.04.001. Epub 2019 Apr 14.
Effective ventilation of the lungs is essential in mediating pulmonary vasodilation at birth to allow effective gas exchange and an increase in systemic oxygenation. Unsuccessful transition prevents the increase in pulmonary blood flow after birth resulting in hypoxemia and persistent pulmonary hypertension of the newborn (PPHN). Management of neonates with PPHN includes ventilation of the lungs with supplemental oxygen to correct hypoxemia. Optimal oxygenation should meet oxygen demand to the tissues and avoid hypoxic pulmonary vasoconstriction (HPV) while preventing oxidative stress. The optimal target for oxygenation in PPHN is not known. Animal models have demonstrated that PaO<45 mmHg exacerbates HPV. However, there are no practical methods of assessing oxygen levels associated with oxidant stress. Oxidant stress can be due to free radical generation from underlying lung disease or from free radicals generated by supplemental oxygen. Free radicals act on the nitric oxide pathway reducing cGMP and promoting pulmonary vasoconstriction. Antioxidant therapy improves systemic oxygenation in an animal model of PPHN but there are no clinical trials to support such therapy. Targeting preductal SpO between 90 and 97% and PaO at 50-80 mmHg appears prudent in PPHN but clinical trials to support this practice are lacking. Preterm infants with PPHN present unique challenges due to lack of antioxidant defenses and functional and structural immaturity of the lungs. This review highlights the need for additional studies to mitigate the impact of oxidative stress in the lung and pulmonary vasculature in PPHN.
有效的肺部通气对于介导出生时的肺血管扩张至关重要，以实现有效的气体交换和全身氧合增加。如果过渡不成功，会阻止出生后肺血流量增加，导致低氧血症和新生儿持续性肺动脉高压（PPHN）。PPHN 新生儿的管理包括通过补充氧气来通气肺部，以纠正低氧血症。最佳氧合应满足组织的氧气需求，避免低氧性肺血管收缩（HPV），同时预防氧化应激。PPHN 中氧合的最佳目标尚不清楚。动物模型表明，PaO<45mmHg 会加重 HPV。然而，目前还没有实用的方法来评估与氧化应激相关的氧气水平。氧化应激可能是由潜在的肺部疾病产生的自由基，或由补充氧气产生的自由基引起的。自由基作用于一氧化氮途径，降低 cGMP 并促进肺血管收缩。抗氧化治疗可改善 PPHN 动物模型的全身氧合，但没有临床试验支持这种治疗。在 PPHN 中，将导管前 SpO 目标值设定在 90%至 97%之间，PaO 目标值设定在 50-80mmHg 似乎是谨慎的，但缺乏支持这种实践的临床试验。PPHN 的早产儿由于缺乏抗氧化防御能力以及肺部和肺血管的功能和结构不成熟，带来了独特的挑战。这篇综述强调了需要开展更多研究，以减轻氧化应激对 PPHN 中肺部和肺血管的影响。
