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INNOVATIVE METHODOLOGY

Surfactant disaturated phosphatidylcholine kinetics in infants with bronchopulmonary dysplasia measured with stable isotopes and a two-compartment model

Departments of ¹Pediatrics and ²Information Engineering, University of Padova, Padova; ³Division of Neonatology, Presidio Salesi, Ospedali Riuniti Ancona, Ancona, Italy; and ⁴Childhood Nutrition Research Centre, Institute of Child Health, University College London, London, United Kingdom

Submitted 27 December 2004 ; accepted in final form 15 March 2005

We previously found a shorter surfactant disaturated phosphatidylcholine palmitate (DSPC-PA) half-life in infants with bronchopulmonary dysplasia (BPD) by using a single stable isotope tracer and simple formulas based on a one-exponential fit of the final portion of the enrichment decay curve. The aim of this study was to apply noncompartmental and compartmental analysis on the entire enrichment decay curve of DSPC-PA and to compare the kinetic data with our previous results. We analyzed 10 preterm newborns with BPD (gestational age 26 ± 0.6 wk, weight 777 ± 199 g) and 6 controls (gestational age 26 ± 1.4 wk, weight 787 ± 259 g). All took part in our previous study. Endotracheal ¹³C-labeled dipalmitoyl phosphatidylcholine was administered, and the ¹³C-enrichment of surfactant DSPC-PA was measured from serial tracheal aspirates by gas chromatography-mass spectrometry. Noncompartmental and compartmental models were numerically identified from the tracer-to-tracee ratio and kinetic parameters related to the accessible (pool accessible to sampling, likely to be the lung alveolar pool) and to the nonaccessible pools (pools not accessible to samplings, likely to be the intracellular storage pool) were estimated in the two study groups. Comparison was performed by Mann-Whitney test. A two-compartment model provided the most reliable assessment of DSPC-PA kinetics. In BPD vs. controls, mean ± SE residence time of DSPC-PA in the accessible was 17.5 ± 2.6 vs. 32.2 ± 6.4 h (P < 0.05), whereas it was 49.7 ± 3.5 vs. 54.4 ± 3.9 h (NS, not significant) in the nonaccessible pool; DSPC-PA recycling was 0.26 ± 0.05 vs. 0.43 ± 0.04% (NS), respectively. A two-compartment model of surfactant DSPC-PA kinetics allowed a thorough assessment of DSPC-PA kinetics, including masses, synthesis, and fluxes between pools. The most important findings of this study are that in BPD infants DSPC-PA loss from the alveolar pool was higher and recycling through the intracellular pool lower than in controls.

pulmonary surfactant; stable isotopes; phospholipids