Ballard Philip L, Keller Roberta L, Black Dennis M, Durand David J, Merrill Jeffrey D, Eichenwald Eric C, Truog William E, Mammel Mark C, Steinhorn Robin, Ryan Rita M, Courtney Sherry E, Horneman Hart, Ballard Roberta A
Department of Pediatrics, University of California, San Francisco, California.
Department of Epidemiology and Biostatistics, University of California, San Francisco, California.
Am J Perinatol. 2015 Feb;32(3):225-32. doi: 10.1055/s-0034-1382255. Epub 2014 Jun 26.
Inhaled nitric oxide (iNO) has been tested to prevent bronchopulmonary dysplasia (BPD) in premature infants, however, the role of cyclic guanosine monophosphate (cGMP) is not known. We hypothesized that levels of NO metabolites (NOx) and cGMP in urine, as a noninvasive source for biospecimen collection, would reflect the dose of iNO and relate to pulmonary outcome.
Studies were performed on 125 infants who required mechanical ventilation at 7 to 14 days and received 24 days of iNO at 20-2 ppm. A control group of 19 infants did not receive iNO.
In NO-treated infants there was a dose-dependent increase of both NOx and cGMP per creatinine (maximal 3.1- and 2-fold, respectively, at 10-20 ppm iNO) compared with off iNO. NOx and cGMP concentrations at both 2 ppm and off iNO were inversely related to severity of lung disease during the 1st month, and the NOx levels were lower in infants who died or developed BPD at term. NOx was higher in Caucasian compared with other infants at all iNO doses.
Urinary NOx and cGMP are biomarkers of endogenous NO production and lung uptake of iNO, and some levels reflect the severity of lung disease. These results support a role of the NO-cGMP pathway in lung development.
吸入一氧化氮（iNO）已被用于预防早产儿支气管肺发育不良（BPD），然而，环磷酸鸟苷（cGMP）的作用尚不清楚。我们假设，作为生物样本采集的非侵入性来源，尿液中NO代谢产物（NOx）和cGMP的水平将反映iNO的剂量，并与肺部结局相关。
对125名在7至14天需要机械通气并接受24天20 - 2 ppm iNO治疗的婴儿进行了研究。19名婴儿的对照组未接受iNO治疗。
与未使用iNO相比，接受NO治疗的婴儿中，每肌酐的NOx和cGMP均呈剂量依赖性增加（在10 - 20 ppm iNO时分别最大增加3.1倍和2倍）。在第1个月期间，2 ppm和未使用iNO时的NOx和cGMP浓度均与肺部疾病的严重程度呈负相关，足月时死亡或发生BPD的婴儿的NOx水平较低。在所有iNO剂量下，白种婴儿的NOx水平均高于其他婴儿。
尿NOx和cGMP是内源性NO产生和iNO肺摄取的生物标志物，某些水平反映了肺部疾病的严重程度。这些结果支持NO - cGMP途径在肺发育中的作用。
