Surfactant disaturated-phosphatidylcholine kinetics in acute respiratory distress syndrome by stable isotopes and a two compartment model

Paola E Cogo^*¹ , Gianna Maria Toffolo^*² , Carlo Ori^*³ , Andrea Vianello^*⁴ , Marco Chierici^*² , Antonina Gucciardi^*¹ , Claudio Cobelli^*² , Aldo Baritussio^*⁵ and Virgilio P Carnielli^*⁶^,7

¹Department of Pediatrics, University of Padova, Padova, Italy

²Department of Information Engineering, University of Padova, Italy

³Department of Pharmacology, Anaesthesia and Critical Care, University of Padova, Padova, Italy

⁴Respiratory Unit, General Medical Hospital, Padova, Italy

⁵Department of Medical and Surgical Sciences, University of Padova, Padova, Italy

⁶Neonatal Division, Salesi Children's Hospital, Ancona, Italy

⁷Nutrition Unit, Institute of Child Health and Great Ormond Street Hospital, London, UK

author email corresponding author email* Contributed equally

Respiratory Research 2007, 8:13doi:10.1186/1465-9921-8-13


Published:	21 February 2007

Abstract

Background

In patients with acute respiratory distress syndrome (ARDS), it is well known that only part of the lungs is aerated and surfactant function is impaired, but the extent of lung damage and changes in surfactant turnover remain unclear. The objective of the study was to evaluate surfactant disaturated-phosphatidylcholine turnover in patients with ARDS using stable isotopes.

Methods

We studied 12 patients with ARDS and 7 subjects with normal lungs. After the tracheal instillation of a trace dose of ¹³C-dipalmitoyl-phosphatidylcholine, we measured the ¹³C enrichment over time of palmitate residues of disaturated-phosphatidylcholine isolated from tracheal aspirates. Data were interpreted using a model with two compartments, alveoli and lung tissue, and kinetic parameters were derived assuming that, in controls, alveolar macrophages may degrade between 5 and 50% of disaturated-phosphatidylcholine, the rest being lost from tissue. In ARDS we assumed that 5–100% of disaturated-phosphatidylcholine is degraded in the alveolar space, due to release of hydrolytic enzymes. Some of the kinetic parameters were uniquely determined, while others were identified as lower and upper bounds.

Results

In ARDS, the alveolar pool of disaturated-phosphatidylcholine was significantly lower than in controls (0.16 ± 0.04 vs. 1.31 ± 0.40 mg/kg, p < 0.05). Fluxes between tissue and alveoli and de novo synthesis of disaturated-phosphatidylcholine were also significantly lower, while mean resident time in lung tissue was significantly higher in ARDS than in controls. Recycling was 16.2 ± 3.5 in ARDS and 31.9 ± 7.3 in controls (p = 0.08).

Conclusion

In ARDS the alveolar pool of surfactant is reduced and disaturated-phosphatidylcholine turnover is altered.