Estimating the contribution of surfactant replacement therapy to the alveolar pool: An in vivo study based on 13C natural abundance in rabbits

• Published in: Journal of mass spectrometry. Vol. 53; no. 7; pp. 560 - 564
• Main Authors: Giambelluca, Sonia, Ricci, Francesca, Simonato, Manuela, Correani, Alessio, Casiraghi, Costanza, Storti, Matteo, Cogo, Paola, Salomone, Fabrizio, Carnielli, Virgilio Paolo
• Format: Journal Article
• Language: English
• Published: Bognor Regis Wiley Subscription Services, Inc 01.07.2018
• Subjects: 13C natural abundance; Abundance; Alveoli; animal models; Bronchus; carbon; Carbon 13; Feasibility studies; GC‐C‐IRMS; humans; In vivo methods and tests; in vivo studies; Infants; Isotopes; Isotopic enrichment; Kinetics; Lecithin; Lungs; Mass spectrometry; Mass spectroscopy; Mineral nutrients; Molecular chains; Nutrients; Organic chemistry; palmitates; Palmitic acid; Pharmacology; Phosphatidylcholine; Phospholipids; premature birth; Rabbits; RDS; stable isotope; stable isotopes; surfactant; Surfactants; therapeutics; Therapy; tracer techniques; Tracers
• DOI: 10.1002/jms.4088
• ISSN: 1076-5174

Variation of the isotopic abundance of selected nutrients and molecules has been used for pharmacological and kinetics studies under the premise that the administered molecule has a different isotopic enrichment from the isotopic background of the recipient subject. The aim of this study is to test the feasibility of assessing the contribution of exogenous surfactant phospholipids to the endogenous alveolar pool in vivo after exogenous surfactant replacement therapy in rabbits. The study consisted in measuring the consistency of 13C/12C ratio of disaturated‐phosphatidylcholine palmitate (DSPC‐PA) in 7 lots of poractant alfa, produced over a year, and among bronchoalveolar lavages of 20 rabbits fed with a standard chow. A pilot study was performed in a rabbit model of lavage‐induced surfactant deficiency: 7 control rabbits and 4 treated with exogenous surfactant. The contribution of exogenous surfactant to the alveolar pool was assessed after intra‐tracheal administration of 200 mg/kg of poractant alfa. The 13C content of DSPC‐PA was measured by isotope ratio mass spectrometry. The mean DSPC‐PA 13C/12C ratio of the 7 lots of poractant alfa was −18.8‰ with a SD of 0.1‰ (range: −18.9‰; −18.6‰). The mean 13C/12C ratio of surfactant DSPC recovered from the lung lavage of 20 rabbits was −28.8 ± 1.2‰ (range: −31.7‰; −25.7‰). The contribution of exogenous surfactant to the total alveolar surfactant could be calculated in the treated rabbits, and it ranged from 83.9% to 89.6%. This pilot study describes a novel method to measure the contribution of the exogenous surfactant to the alveolar pool. This method is based on the natural variation of 13C, and therefore it does not require the use of chemically synthetized tracers. This method could be useful in human research and especially in surfactant replacement studies in preterm infants.