EFFECTS OF INHALED NITRIC OXIDE(NO) ON OXIDANT INJURY IN INFANTS W/RESP. FAILURE

吸入一氧化氮（INO）是一种令人兴奋的新疗法，用于新生儿严重肺部疾病，在大型临床研究中取得了巨大成功。一氧化氮（NO）是一种分子，以前只知道作为一种环境污染物发现在汽车尾气和香烟烟雾。然而，已经发现NO可以扩张肺中的血管，使受伤的肺能够更有效地转移氧气和二氧化碳。其在新生儿中使用的长期影响尚不清楚。该项目建议调查INO治疗是否会导致与长时间暴露于氧气中类似的损伤证据。这种类型的损伤的证据将通过对接受NO和氧气以及仅接受氧气的婴儿的血液进行实验室研究来寻找。这些结果也将与正常婴儿的样本进行比较。样本取自帕卡德儿童医院重症监护室的婴儿，研究在Phyllis登内里博士的实验室进行。初步结果表明，与接受高氧浓度的婴儿相比，接受NO的婴儿氧化损伤和抗氧化防御能力明显增加。虽然NO似乎是严重呼吸衰竭的重要治疗方法，但长期使用可能与慢性肺病等不良后果有关。该项目有能力通过增加有关INO治疗毒性的知识使儿童受益。如果INO治疗发现显著异常，则该信息对于指导该治疗在新生儿中的进一步使用至关重要。

Inhaled nitric oxide (INO) is an exciting new therapy being used in newborns with severe lung disease which has shown great success in large clinical studies. Nitric oxide (NO) was a molecule previously known only as an environmental pollutant found in car exhaust and cigarette smoke. However, NO has been found to dilate the blood vessels in the lung enabling injured lungs to transfer oxygen and carbon dioxide more effectively. The long term effects of its use in newborn infants are not known. The project proposes to investigate whether INO therapy causes evidence of injury similar to that which is seen with prolonged exposure to oxygen. Evidence of this type of injury will be sought by doing laboratory studies on the blood of infants receiving NO and oxygen and oxygen alone. These results will also be compared to samples from normal infants. The samples are drawn from infants in the Intensive Care Nursery at Packard Children's Hospital and the studies are processed in Dr. Phyllis Dennery's laboratory. Preliminary results demonstrate a definite increase in oxidative injury and depleted antioxidant defenses in infants receiving NO when compared to infants receiving high oxygen concentrations. While NO appears to be an important therapy for severe respiratory failure, prolonged use may be associated with adverse consequences such as chronic lung disease. This project has the ability to benefit children by increasing the knowledge about the toxicities of INO therapy. If signficant abnormalities are found with INO therapy, this information will be critical to guide further use of this therapy in newborns.