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Endogenous surfactant turnover in preterm infants measured with stable isotopes
J E Bunt1, L J Zimmermann, J L Wattimena
1Department of Pediatrics, Sophia Children's Hospital, Erasmus University Rotterdam, The Netherlands.
Insights
Preterm infants utilize glucose for surfactant phosphatidylcholine (PC) synthesis. This study quantifies surfactant PC palmitate production and turnover rates in vivo using stable isotope labeling.
Area of Science:
- Neonatal Physiology
- Biochemistry
- Metabolic Research
Background:
- Surfactant deficiency is a major cause of respiratory distress in preterm infants.
- Understanding surfactant synthesis and turnover is crucial for managing neonatal respiratory disorders.
Purpose of the Study:
- To investigate in vivo surfactant synthesis and turnover in preterm infants.
- To quantify the contribution of glucose to surfactant phosphatidylcholine (PC) palmitate synthesis.
- To establish a novel method for studying surfactant metabolism using stable isotopes.
Main Methods:
- Stable isotope infusion of [U-13C]glucose in six preterm infants within 24 hours of birth.
- Analysis of 13C-enrichment in surfactant PC palmitate from tracheal aspirates using gas chromatography-combustion interface-isotope ratio mass spectrometry.
- Calculation of fractional synthesis rate (FSR), absolute production rate, and half-life of surfactant PC palmitate.
Main Results:
- Significant incorporation of 13C from glucose into surfactant PC palmitate was observed.
- Palmitate enrichment reached maximum levels between 48 to 96 hours after label infusion.
- The fractional synthesis rate of surfactant PC palmitate from glucose was 2.7 ± 1.3%/d, with a calculated production rate of 4.2 mg/kg/d and a half-life of 113 ± 25 hours.
Conclusions:
- Stable isotope tracing of [U-13C]glucose provides a safe and effective method to study endogenous surfactant production and turnover in preterm infants.
- This approach offers valuable insights into surfactant metabolism, applicable to preterm infants, children, and adults.
- The findings contribute to a better understanding of neonatal respiratory physiology and potential therapeutic targets.
Abstract:
We studied surfactant synthesis and turnover in vivo in preterm infants using the stable isotope [U-13C]glucose, as a precursor for the synthesis of palmitic acid in surfactant phosphatidylcholine (PC). Six preterm infants (birth weight, 916 +/- 244 g; gestational age, 27.7 +/- 1.7 wk) received a 24-h [U-13C]glucose infusion on the first day of life. The 13C-enrichment of palmitic acid in surfactant PC, obtained from tracheal aspirates, was measured by gas chromatography-combustion interface-isotope ratio mass spectrometry. We observed a significant incorporation of carbon-13 from glucose into surfactant PC palmitate. PC palmitate became enriched after 19.4 +/- 2.3 (16.5 to 22.3) h and reached maximum enrichment at 70 +/- 18 (48 to 96) h after the start of the label infusion. The fractional synthesis rate (FSR) of surfactant PC palmitate from glucose was 2.7 +/- 1.3%/d. We calculated the absolute production rate of surfactant PC to be 4.2 mg/kg/d, and the half-life to be 113 +/- 25 (87 to 144) h. Data on endogenous surfactant production and turnover were obtained for the first time in human infants with the use of stable isotopes. This novel and safe method could be applied to address many important issues concerning surfactant metabolism in preterm infants, children, and adults.