The 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 hernia [CDH; birth weight, 3.4 0.2; gestational age, 39.8 0.4 wk] and 6 age-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 di- palmitoyl-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 · kg1 · d1; 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 · kg1 · d1. No significant differences were found between control subjects and infants with CDH. DSPC turnover 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. (Pediatr Res 56: 184–190, 2004) Abbreviations CDH, congenital diaphragmatic hernia DPPC, di-palmitoyl-phosphatidylcholine DSPC, disaturated-phosphatidylcholine ECMO, extracorporeal membrane oxygenation FIO2, fraction of inspired oxygen FSR, fractional synthesis rate PAO2, alveolar oxygen pressure PaO2, arterial oxygen pressure SP-A, surfactant protein A
Dual stable isotope tracer method for the measurement of surfactant disaturated-phosphatidylcholine net synthesis in infants with congenital diaphragmatic hernia
P. Midrio;ORI, CARLO;
2004
Abstract
The 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 hernia [CDH; birth weight, 3.4 0.2; gestational age, 39.8 0.4 wk] and 6 age-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 di- palmitoyl-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 · kg1 · d1; 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 · kg1 · d1. No significant differences were found between control subjects and infants with CDH. DSPC turnover 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. (Pediatr Res 56: 184–190, 2004) Abbreviations CDH, congenital diaphragmatic hernia DPPC, di-palmitoyl-phosphatidylcholine DSPC, disaturated-phosphatidylcholine ECMO, extracorporeal membrane oxygenation FIO2, fraction of inspired oxygen FSR, fractional synthesis rate PAO2, alveolar oxygen pressure PaO2, arterial oxygen pressure SP-A, surfactant protein APubblicazioni consigliate
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