Hamon Isabelle, Fresson Jeanne, Nicolas Marie-Benedicte, Buchweiller Marie-Christine, Franck Patricia, Hascoet Jean-Michel
Neonatology Division, Maternite Regionale Universitaire de Nancy, Nancy 54045, France.
Pediatr Res. 2005 May;57(5 Pt 1):637-43. doi: 10.1203/01.PDR.0000156507.03879.19. Epub 2005 Mar 3.
Inhaled nitric oxide (iNO) improves oxygenation in premature infants, but concern has been raised about its potential oxidative toxicity. We designed this study to assess the oxidative balance in premature infants who were exposed to low dose iNO and the relationship with their clinical outcome on day 28 of life. A total of 274 infants who were <32 wk gestation were randomized at birth to receive 5 ppm of iNO if they presented with hypoxemic respiratory failure. Nonhypoxemic infants were studied as the reference group. Blood samples were withdrawn 24 h apart, within the first 4 d of life, to assess malondialdehyde (MDA) concentration as oxidative stress marker and total plasmatic glutathione (GSH), intraerythrocyte GSH peroxidase, and GSH reductase activities as antioxidant defenses. After 24 h, the rise in MDA was blunted in the iNO group compared with controls and was close to the reference infants. Conversely, GSH was more stable in the iNO group, when there was no difference for the GSH peroxidase and GSH reductase activities. On day 28, Oxygen dependence was linked with a higher increase in MDA as was the risk for death, whereas intraventricular hemorrhage was associated with a higher initial drop in GSH. Early low-dose iNO in hypoxemic preterm infants improves oxidative balance and seems to be clinically beneficial up to day 28 of life.
吸入一氧化氮(iNO)可改善早产儿的氧合,但人们对其潜在的氧化毒性表示担忧。我们设计了这项研究,以评估暴露于低剂量iNO的早产儿的氧化平衡及其与出生后第28天临床结局的关系。共有274名孕周<32周的婴儿在出生时被随机分组,若出现低氧性呼吸衰竭则接受5 ppm的iNO治疗。非低氧血症婴儿作为参照组。在出生后的前4天内,每隔24小时采集血样,以评估作为氧化应激标志物的丙二醛(MDA)浓度以及作为抗氧化防御指标的血浆总谷胱甘肽(GSH)、红细胞内谷胱甘肽过氧化物酶和谷胱甘肽还原酶活性。24小时后,与对照组相比,iNO组MDA的升高受到抑制,且接近参照组婴儿。相反,iNO组的GSH更稳定,而谷胱甘肽过氧化物酶和谷胱甘肽还原酶活性无差异。在第28天,氧依赖与MDA的更高升高以及死亡风险相关,而脑室内出血与GSH的更高初始下降有关。低氧血症早产儿早期低剂量使用iNO可改善氧化平衡,在出生后第28天似乎具有临床益处。