Submitted on December 27, 2004
Accepted on March 15, 2005
Surfactant disaturated-phosphatidylcholine kinetics in infants with bronchopulmonary dysplasia measured with stable isotopes anda a two compartment model
Paola E. Cogo1*, Gianna M. Toffolo2, Antonina Gucciardi1, Arianna Benetazzo1, Claudio Cobelli2, and Virgilio P. Carnielli3
1 Department of Pediatrics, University of Padova, Padova, Italy
2 Department of Information Engineering, University of Padova, Padova, Italy
3 Division of Neonatology, Salesi Children Hospital, Ancona, Italy
* To whom correspondence should be addressed. E-mail: cogo{at}pediatria.unipd.it.
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 weeks, weight 777±199 g) and 6 controls (gestational age 26±1.4 weeks, weight 787± 259 g). All took part in our previous study. Endotracheal 13C labeled dipalmitoyl-phosphatidylcholine (DPPC) 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 (ttr) and kinetic parameters related to the accessible (pool accessible to sampling, likely to be the lung alveolar pool) and to the non accessible pools (pool not accessible to sampling 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±SEM 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 (n.s., not significant) in the non accessible pool; DSPC-PA recycling was 0.26±0.05 % vs. 0.43±0.04 % (n.s.) 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.
