In Vivo Metabolism of Pulmonary Surfactant in Infants

婴儿肺表面活性剂的体内代谢

• 批准号: 6886704
• 负责人: AARON HAMVAS
• 金额: $ 25.6万
• 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 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6886704
• 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：（扫描自申请人描述）：呼吸窘迫

项目成果

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation.

先天性膈疝新生儿在体外膜氧合过程中表面活性剂磷脂酰胆碱合成减少。

• DOI: 10.1007/s00134-009-1564-7
• 发表时间: 2009
• 期刊: Intensive care medicine
• 影响因子: 38.9
• 作者: Janssen,DaphneJ;Zimmermann,LucJ;Cogo,Paola;Hamvas,Aaron;Bohlin,Kajsa;Luijendijk,IngridH;Wattimena,Darcos;Carnielli,VirgilioP;Tibboel,Dick
• 通讯作者: Tibboel,Dick