Disaturated-phosphatidylcholine Kinetics Research Articles

Surfactant protein B and A concentrations are increased in neonatal pneumonia.

Background:Term newborns with pneumonia show a reduced pulmonary compliance due to multiple and ill-defined factors. Surfactant proteins’ (SPs) changes could have a role in the reduced compliance but the matter is still unsettled. The aim of this study was to clarify the meaning of SPs changes during pneumonia in term newborns.Methods:In 28 term ventilated newborns, 13 with pneumonia and 15 with no lung disease, we measured SP-B, SP-A, disaturated-phosphatidylcholine (DSPC), and total phospholipids (PL) concentrations in tracheal aspirates at intubation and close to extubation. We also measured DSPC kinetics using (U-13C-PA)dipalmitoyl-phosphatidylcholine.Results:At baseline, SP-B, expressed as % of PL, was significantly different between the groups, being 3.5-fold higher in pneumonia than controls. Conversely, SP-A did not vary between the groups. At extubation, SP-B and SP-A concentrations had decreased significantly in newborns with pneumonia, while there was no significant change in controls. DSPC t1/2 was significantly shorter in the pneumonia group (11.8 (5.5–19.8) h vs. 26.6 (19.3–63.6) h, P = 0.011).Conclusion:In term newborns with pneumonia, SP-B increases with respect to PL, and DSPC is turned over at a faster rate. Disease’s resolution is associated with the restoration of the normal ratio between SP-B and PL.Supplementary informationThe online version of this article (doi:10.1038/pr.2015.123) contains supplementary material, which is available to authorized users.

403 Surfactant Disaturated-Phosphatidylcholine Kinetics in Pneumonia by Stable Isotopes

Background and AimWhether pulmonary surfactant deficiency or dysfunction contributes to the pathogenesis of neonatal pneumonia is still debated. Aim of our study was to measure surfactant disaturated-phosphatidylcholine (DSPC) kinetics and...

495 Impaired Surfactant Protein B Synthesis in Infants with Congenital Diaphragmatic Hernia

Background: Whether congenital diaphragmatic hernia (CDH) is associated with surfactant deficiency or dysfunction is controversial. Aims: To measure disaturated phosphatidylcholine (DSPC) and surfactant protein B (SP-B) synthesis and metabolism in infants with CDH. Methods: DSPC and SP-B amounts and kinetics were studied in tracheal aspirates (TA) of 12 infants with CDH (BW 2978±447g, GA 38±2 wk) and in 8 GA-matched control infants (BW 3160±350g, GA 38±2 wk). Seventeen infants received a 24h infusion of 13C-leucine, an i.v. bolus of 2H2O and 0.0625% of fluid intake as 2H2O every 12h over the next 48h. Three infants received only 13C-leucine infusion. DSPC and SP-B were isolated from TA. DSPC amounts, 2H-palmitate and 13C-leucine enrichments were measured by gas chromatography mass spectrometry. Results: DSPC amount and kinetics have been measured in 17 newborns, and SP-B kinetics in 18. DSPC median (interquartile range) fractional synthesis rate (FSR) was 5.0 %/day (3.5-8.5) in CDH patients vs 6.1 %/day (5.8-7.0) in controls (p=0.31). DSPC secretion time (ST) was 10.7h (6.9-11.5) vs 7.9h (5.2-14.0) (p=0.65). SP-B FSR was 33.4 %/day (28.4-42.9) vs 52.0 %/ day (40.0-83.4) (p=0.03); SP-B peak time was 26h (24-32) vs 18h (15-21) (p=0.02), both significantly lower in the CDH group. SP-B ST was 6.1h (4.0- 9.9) vs 2.7h (1.1-7.1) (p=0.24), and half life 7.5h (5.2-9.1) vs 11.1h (5.8-17.3) (p=0.33). Conclusions: Decreased and delayed SP-B synthesis was found in newborns with CDH compared to controls while DSPC kinetics was similar in both groups, which may contribute to severe respiratory failure in these patients.

Metabolic precursors of surfactant disaturated-phosphatidylcholine in preterms with respiratory distress

Our objective was to study the metabolic precursors of surfactant disaturated-phosphatidylcholine (DSPC) in preterm infants with respiratory distress syndrome (RDS) on mechanical ventilation. We performed 46 DSPC kinetic studies in 23 preterms on fat-free parenteral nutrition and mechanical ventilation (birth weight = 1167 +/- 451 g, gestational age = 28.5 +/- 2.0 weeks). Eight infants received a simultaneous intravenous infusion of U(13)C-glucose and [16,16,16](2)H-palmitate, eight infants received U(13)C-glucose and (2)H(2)O, and seven received U(13)C-palmitate and (2)H(2)O. Surfactant DSPC kinetics were calculated from the isotopic enrichments of DSPC-palmitate from sequential tracheal aspirates and its metabolic precursors in plasma or urine. DSPC fractional synthesis rate (FSR) was 17 +/- 11, 21 +/- 16, and 15 +/- 6%/day from glucose, palmitate, and body water, respectively (P = 0.36). DSPC-FSR from U(13)C-glucose and (2)H(2)O were significantly correlated and yielded similar estimates (difference of -0.1 +/- 3%) (P = 0.91). The difference in the 15 infants receiving palmitate versus (2)H(2)O or palmitate versus glucose was +6.0 +/- 12%/day (P = 0.21). There was a significant correlation between DSPC-FSRs from plasma glucose and plasma FFA. The contribution of glucose versus palmitate to DSPC-FSR was 49 +/- 20% versus 51 +/- 20%, respectively. Plasma glucose and FFA showed similar contributions to DSPC-FSR in infants with RDS and fat-free parenteral nutrition. FSRs from (2)H(2)O or glucose were highly correlated.

Pulmonary surfactant disaturated-phosphatidylcholine (DSPC) turnover and pool size in newborn infants with congenital diaphragmatic hernia (CDH).

In animal CDH models, surfactant deficiency contributes to the pathophysiology of the condition but information on human disease is very limited. The aim of our study was to investigate surfactant kinetics in CDH newborns. We studied surfactant disaturated-phosphatidylcholine (DSPC) half-life, turnover and apparent pool size by stable isotope methodology in CDH newborns with no ExtraCorporeal Membrane Oxygenation (ECMO) support (n = 13, birth weight (BW) 3.2 +/- 2.2 kg, gestational age (GA) 39 +/- 0.4 wks, postnatal age 43 +/- 11 h) and in 8 term infants with no lung disease (CONTROLS, BW 2.7 +/- 0 kg, GA 38 +/- 0.8 wks, postnatal age 96 +/- 26 h). We administered a trace dose of 13C-palmitic acid dipalmitoyl-phosphatidylcholine (DPPC) through the endotracheal (ET) tube and we measured DSPC kinetics by gas chromatography-mass spectrometry from DSPC13C-enrichment decay curves obtained from sequential tracheal aspirates. DSPC amount from tracheal aspirates (TA-DSPC) was measured by gas chromatography. In CDH infants DSPC half-life was shorter (24 +/- 4 and 53 +/- 11 h, p = 0.01), turnover faster (0.6 +/- 0.1 and 1.5 +/- 0.3 d-1 p = 0.01), apparent pool size smaller (34 +/- 6 and 57 +/- 7 mg/kg body weight, p = 0.02) and tracheal aspirates DSPC amount lower (2.4 +/- 0.4 and 4.6 +/- 0.5 mg/mL Epithelial Lining Fluid (ELF), p = 0.007) than in CONTROLS. In conclusion surfactant kinetics is grossly abnormal in mechanically ventilated CDH. Whether alterations of DSPC kinetics in CDH infants are caused by a primary surfactant deficiency or are secondary to oxygen therapy and ventilator support has still to be determined.

Surfactant synthesis and kinetics in infants with congenital diaphragmatic hernia.

In animal models of congenital diaphragmatic hernia (CDH), surfactant deficiency contributes to the pathophysiology of the disease; however, information on CDH in humans is limited. We compared surfactant disaturated phosphatidylcholine (DSPC) synthesis and metabolism, by stable isotope technology, in newborn infants with CDH and in control subjects. DSPC amount, total proteins, and surfactant protein-A (SP-A) from tracheal aspirates were also measured. DSPC and SP-A were significantly lower in 14 infants with CDH than in the eight control subjects. Mean DSPC was 2.3 +/- 1.3 mg/ml of epithelial lining fluid (ELF) in infants with CDH and 4.6 +/- 1.5 mg/ml of ELF in control subjects (p = 0.001). Mean SP-A in infants with CDH and in control subjects was 16.2 +/- 9.3 and 61.2 +/- 30.6 microg/ml of ELF, respectively (p = 0.03). DSPC kinetics was measured in 12 of 14 infants with CDH and in 5 of 8 control subjects. Secretion time was 8.3 +/- 5.5 and 8.5 +/- 2.5 hours and peak time 51.9 +/- 15.2 and 51 +/- 13 hours in infants with CDH and in control subjects, respectively. Fractional synthesis rate was not different for infants with CDH and control subjects (p = 0.4). In conclusion, surfactant DSPC synthesis and kinetics were not significantly deranged in infants with CDH compared with control subjects. Other factors, such as lower surface area or increased DSPC catabolism, may contribute to surfactant pool alteration in CDH.