A dual stable isotope tracer method for the measurement of surfactant disaturated-phosphatidylcholine net synthesis in infants with congenital diaphragmatic hernia

he aim of the study was to measure for the first time in humans surfactant disaturated-phosphatidylcholine (DSPC) net synthesis and kinetics by using a novel, dual stable isotope tracer approach. Ten infants with congenital diaphragmatic hemia [CDH; birth weight, 3.4 ± 0.2; gestational age, 39.8 ± 0.4 wk] and 6 4ge-matched control subjects with no lung disease (birth weight, 3.2 0.3 kg; gestational age, 39.1 ± 1.1 wk), all of whom were admitted to the neonatal intensive care unit (Padua, Italy), were studied. All infants received simultaneously an intratracheal (carbon-13 dipalmitoyl- phosphatidylcholine) and an i.v. (deuterated palmitic acid) stable isotope tracer. Isotopic enrichment curves of DSPC from sequential tracheal aspirates were analyzed by mass spectrometry. DSPC kinetic data were expressed as mean ± SEM and compared by the Mann-Whitney test. DSPC net synthesis from plasma palmitate was nearly identical in infants with CDH and control subjects (8.6 ± 2.2 and 8.1 ± 1.5 mg·kg-1·d -1; P = 0.7). DSPC apparent pool size was 36.7 ± 7.5 and 58.5 ± 9.1 mg/kg (P = 0.07) and half-life was 26.7 ± 4.5 and 50.3 ± 9.7 h (P = 0.03) in infants with CDH and control subjects, respectively. Both DSPC turnover and percentage of catabolism/recycling significantly correlated with duration of mechanical ventilation. In conclusion, the measurements of net DSPC synthesis and catabolism/recycling were reported for the first time in humans. Mean net DSPC synthesis was ∼8 mg·kg-1·d-1. No significant differences were found between control subjects and infants with CDH. DSPC tumover was faster in infants with CDH presumably reflecting an increased DSPC catabolism/recycling. Whether this may ultimately lead to a secondary surfactant deficiency in infants with CDH is still to be ascertained.