Cogo P E, Carnielli V P, Bunt J E, Badon T, Giordano G, Zacchello F, Sauer P J, Zimmermann L J
Department of Paediatrics, University of Padua, Italy.
Pediatr Res. 1999 Feb;45(2):242-6. doi: 10.1203/00006450-199902000-00015.
Little is known about endogenous surfactant metabolism in infants, because radioactive isotopes used for this purpose in animals cannot be used in humans. We developed a novel and safe method to measure the endogenous surfactant kinetics in vivo in humans by using stable isotope labeled fatty acids. We infused albumin-bound [U-13C]palmitic acid (PA) and [U-13C]linoleic acid (LLA) for 24 h in eight critically ill infants (mean+/-SD: weight: 3.7+/-1.3 kg: age: 51.3+/-61.6 d) who required mechanical ventilation. The 13C enrichment of PA and LLA in surfactant phosphatidylcholine (PC), obtained from tracheal aspirates, was measured by gas chromatography combustion interface-isotope ratio mass spectrometry. We measured a significant incorporation of both 13C-PA and 13C-LLA into surfactant PC. PC-PA and PC-LLA became enriched after 8.7+/-4.9 h (range: 3.4-17.3) and 10.0+/-7.2 h (range: 3.0-22.4), respectively; the times at maximum enrichment were 49.2+/-8.9 and 45.6+/-19.3 h, respectively. The fractional synthesis rate of surfactant PC-PA ranged from 0.4 to 3.4% per h, whereas the fractional synthesis rate of PC-LLA ranged from 0.5 to 3.8% per h. The surfactant PC-PA and PC-LLA half-lives ranged from 16.8 to 177.7 and 23.8 to 144.4 h, respectively. This method provides new data on surfactant metabolism in infants requiring mechanical ventilation. We found that synthesis of surfactant from plasma PA and LLA is a slow process and that there were marked differences in PC kinetics among infants. This variability could be related to differences in lung disease and could affect the clinical course of the respiratory failure.
由于用于动物体内此项研究的放射性同位素不能用于人体,因此关于婴儿内源性表面活性剂代谢的了解甚少。我们开发了一种新颖且安全的方法,通过使用稳定同位素标记的脂肪酸来测量人体体内的内源性表面活性剂动力学。我们对八名需要机械通气的重症婴儿(平均±标准差:体重:3.7±1.3千克;年龄:51.3±61.6天)静脉输注结合白蛋白的[U-13C]棕榈酸(PA)和[U-13C]亚油酸(LLA)24小时。通过气相色谱燃烧接口-同位素比率质谱法测量从气管吸出物中获得的表面活性剂磷脂酰胆碱(PC)中PA和LLA的13C丰度。我们测量到13C-PA和13C-LLA均大量掺入表面活性剂PC中。PC-PA和PC-LLA分别在8.7±4.9小时(范围:3.4 - 17.3)和10.0±7.2小时(范围:3.0 - 22.4)后富集;最大富集时间分别为49.2±8.9小时和45.6±19.3小时。表面活性剂PC-PA的分数合成率为每小时0.4%至3.4%,而PC-LLA的分数合成率为每小时0.5%至3.8%。表面活性剂PC-PA和PC-LLA的半衰期分别为16.8至177.7小时和23.8至144.4小时。该方法为需要机械通气的婴儿的表面活性剂代谢提供了新数据。我们发现从血浆PA和LLA合成表面活性剂是一个缓慢的过程,并且婴儿之间的PC动力学存在显著差异。这种变异性可能与肺部疾病的差异有关,并可能影响呼吸衰竭的临床病程。