In Vivo Metabolism of Pulmonary Surfactant in Infants

婴儿肺表面活性剂的体内代谢

• 批准号: 6331907
• 负责人: AARON HAMVAS
• 金额: $ 26.96万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6331907
• 关键词: gas chromatography; human subject; infant human (0-1 year); mass spectrometry; metabolism; patient oriented research; pediatrics; pulmonary surfactants; radiotracer; respiratory distress syndrome of newborn

DESCRIPTION: (Scanned from the applicant's description): Respiratory distress syndrome (RDS) in infants most commonJy results from a quantitative deficiency of pulmonary surfactant after premature birth. Failure of exogenous surfactant replacement to reconstitute pulmonary function in up to 50 percent of infants with RDS suggests that mechanisms unrelated to quantitative deficiencies in pulmonary surfactant may disrupt surfactant metabolism in a subgroup of infants with lethal RDS. Preliminary data from studies utilizing naturally occurring, stable, non-radioactive isotope labeled metabolic precursors of phospholipid synthesis suggest two alternative mechanisms, which depend on estimates of the surfactant pool size, for disrupted surfactant metabolism in lethal RDS: 1) if surfactant pool sizes are smaller in infants with lethal RDS than in those with non-lethal RDS, then infants with lethal RDS have decreased endogenous surfactant production and/or increased surfactant catabolism; or 2) if surfactant pool sizes are similar, then infants with lethal RDS have increased surfactant production and catabolism. Exogenous surfactant enriched with 2H4-choline labeled phosphatidylcholine and intravenous infusions of surfactant phospholipid precursors (administered as U-13C6]glucose, 7,7,8,8-2H4-palmitate, or 1-13C1acetate) and gas chromatography/mass spectrometry (GCJMS) and gas chromatography-combustion interface isotope ratio mass spectrometry (GC-IRMS) will be used to test the hypothesis that: Increased surfactant catabolism characterizes infants with Lethal RDS. To compare surfactant pool sizes in infants with lethal and non-lethal RDS, 2H4-choline enrichment in surfactant obtained from tracheal aspirate samples after intratracheal administration of labeled surfactant will be measured. To compare surfactant production in infants with lethal and non-lethal RDS, the rate of incorporation of 13C and 2H4 into surfactant obtained from tracheal aspirate samples after a 24 hour infusion of 1-13C1acetate and 7,7,8,8-2H4-palmitate will be measured. To compare surfactant catabolism in infants with lethal and non-lethal RDS, the rate of clearance of 13C and 2H4 from surfactant obtained from tracheal aspirate samples will be measured. Premature infants less than 29 weeks gestation, infants less than 1 year of age with refractory respiratory failure who are awaiting lung transplantation, and infants less than 6 months of age with normal lungs who require mechanical ventilation will be studied. Techniques using labeled metabolic precursors of surfactant phospholipid synthesis provide a unique and powerful approach to evaluate disruption of surfactant metabolism and will lead to specific and clinically useful interventions to restore pulmonary function in infants with RDS.

描述：(根据申请者的描述扫描)：呼吸窘迫 婴儿的综合征(RDS)最常见的原因是数量不足 早产后肺表面活性物质的变化。外源性表面活性物质失效 高达50%的婴儿接受置换以重建肺功能 RDS表明，与数量缺陷无关的机制 肺表面活性物质可能扰乱部分婴儿的表面活性物质代谢 患有致命的呼吸窘迫综合症。来自研究的初步数据，利用自然发生的， 稳定的非放射性同位素标记的磷脂代谢前体 综合提出了两种替代机制，这取决于对 致死性RDS中表面活性物质代谢紊乱的表面活性物质池大小：1)如果 患有致死性RDS的婴儿表面活性物池的大小比那些患有RDS的婴儿小 非致命性RDS，那么患有致命性RDS的婴儿内源性减少 表面活性物质生产和/或表面活性物质分解代谢增加；或2)如果 表面活性物质池大小相似，则患有致命性RDS的婴儿增加 表面活性物质的生产和分解代谢。富含外源表面活性物质 2H4-胆碱标记磷脂酰胆碱与表面活性物质静脉输注 磷脂前体(以U-13C6形式给药)葡萄糖，7，7，8，8-2H4-棕榈酸酯， 或1-13C1乙酸酯)和气相色谱/质谱仪(GCJMS)和气体 气相色谱-燃烧界面同位素比值质谱联用 将被用来检验这样的假设：表面活性物质分解代谢增加 具有致命性RDS的婴儿的特征。要比较表面活性剂池的大小 致死性和非致命性RDS婴儿，表面活性物质中2H4-胆碱升高 从气管内给药后的气管吸液样本中获得 将测量标记的表面活性物质。要比较中国的表面活性物质生产 致死性和非致命性RDS的婴儿，13C和 2H4在24小时后从气管抽吸物样本中获得表面活性物质 将测量1-13C1乙酸酯和7，7，8，8-2H4-棕榈酸酯的输入量。至 比较致死性和非致命性RDS婴儿的表面活性物质分解代谢， 13C和2H4在气管表面活性物质中的清除率 抽出的样本将被测量。29周以下早产儿 妊娠，1岁以下婴儿合并顽固性呼吸衰竭 正在等待肺移植的人，以及6个月以下的婴儿 对肺功能正常的需要机械通风的患者进行研究。 表面活性物质磷脂代谢前体的标记技术 综合提供了一种独特而强大的方法来评估 表面活性物质的代谢，将导致特异性和临床实用 恢复RDS婴儿肺功能的干预措施。