Measurement of pulmonary surfactant disaturated-phosphatidylcholine synthesis in human infants using deuterium incorporation from body water

The aim of the study was to determine surfactant palmitate disaturated-phosphatidylcholine (DSPC-PA) synthesis in vivo in humans by the incorporation of deuterium from total body water into DSPC-PA under steady state condition. We studied three newborns and one infant (body weight (BW) 4.6 ± 2.9 kg, gestational age 37.5 ± 2 weeks, age 9 ± 9 days) and four preterm newborns (BW 1.3 ± 0.6 kg, gestational age 30.3 ± 2.5 weeks, postnatal age 8.8 ± 9.2 h). All infants were mechanically ventilated during the study and the four preterm infants received exogenous surfactant at the start of the study. We administered 0.44 g ²H ₂O/kg BW as a bolus intravenously, followed by 0.0125 g ²H₂O/kg BW every 6 h to maintain deuterium enrichment at plateau over 2 days. Urine samples and tracheal aspirates (TA) were obtained prior to dosing and every 6 h thereafter. Isotopic enrichment curves of DSPC-PA from sequential TA and urine deuterium enrichments were analyzed by Gas Chromatography-Isotope Ratio-Mass Spectrometry (GC-IRMS) and normalized for Vienna Standard Mean Ocean Water. Enrichment data were used to measure DSPC-PA fractional synthesis rate (FSR) from the linear portion of the DSPC-PA enrichment rise over time, relative to plateau enrichment of urine deuterium. Secretion time (ST) was defined as the time lag between the start of the study and the appearance of DSPC-PA deuterium enrichment in TA. Data were given as mean ± SD. All study infants reached deuterium-steady state in urine. DSPC-PA FSR was 6.5 ± 2.8%/day (range 2.6-10.2). FSR for infants who did not receive exogenous surfactant was 5.7 ± 3.5%/day (range 2.6-9.9%/day) and 7.3 ± 2.1%/day (range 5.1-10.2%/day) in the preterms, whereas DSPC-PA ST was 10 ± 10 h and 31 ± 10 h respectively. Surfactant DSPC-PA synthesis can be measured in humans by the incorporation of deuterium from body water. This study is a simpler and less invasive method compared to previously published methods on surfactant kinetics by means of stable isotopes.