17 research outputs found
Surfactant phosphatidylcholine half-life and pool size measurements in premature baboons developing bronchopulmonary dysplasia
Because minimal information is available about surfactant metabolism in
bronchopulmonary dysplasia, we measured half-lives and pool sizes of
surfactant phosphatidylcholine in very preterm baboons recovering from
respiratory distress syndrome and developing bronchopulmonary dysplasia,
using stable isotopes, radioactive isotopes, and direct pool size
measurements. Eight ventilated premature baboons received (2)H-DPPC
(dipalmitoyl phosphatidylcholine) on d 5 of life, and radioactive
(14)C-DPPC with a treatment dose of surfactant on d 8. After 14 d, lung
pool sizes of saturated phosphatidylcholine were measured. Half-life of
(2)H-DPPC (d 5) in tracheal aspirates was 28 +/- 4 h (mean +/- SEM).
Half-life of radioactive DPPC (d 8) was 35 +/- 4 h. Saturated
phosphatidylcholine pool size measured with stable isotopes on d 5 was 129
+/- 14 micro mol/kg, and 123 +/- 11 micro mol/kg on d 14 at autopsy.
Half-lives were comparable to those obtained at d 0 and d 6 in our
previous baboon studies. We conclude that surfactant metabolism does not
change during the early development of bronchopulmonary dysplasia, more
specifically, the metabolism of exogenous surfactant on d 8 is similar to
that on the day of birth. Surfactant pool size is low at birth, increases
after surfactant therapy, and is kept constant during the first 2 wk of
life by endogenous surfactant synthesis. Measurements with stable isotopes
are comparable to measurements with radioactive tracers and measurements
at autopsy
Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation
Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO
Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation
Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO
Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids
Background: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are long-chain polyunsaturated fatty acids (LCPs) that play pivotal roles in growth and neurodevelopment. Objective: We aimed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs. Design: Twenty-two preterm infants were randomly assigned to either the no-LCP group (fed formula without LCPs; n = 11) or the LCP group (fed formula with LCPs; n = 11). Dietary LCPs had higher 13C content than did the endogenously synthesized LCPs, which were derived from linoleic and α-linolenic acids. The 13C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1, 3, and 7 mo. Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated. Results: Percentage AA synthesis was 67.2 ± 7.8%, 35.9 ± 9.8%, and 29.0 ± 10.3%, and that of DHA was 41.7 ± 14.9%, 10.5 ± 8.1%, and 7.4 ± 6.2% at 1, 3, and 7 mo old, respectively. Absolute AA synthesis was 26.7 ± 4.2, 14.4 ± 3.9, and 11.6 ± 4.1mg · kg-1 · d-1 and that of DHA was 12.6 ± 4.5, 3.2 ± 2.5, and 2.3 ± 1.9 mg · kg-1 · d-1 at 1, 3, and 7 mo old, respectively. AA and DHA synthesis decreased significantly (P < 0.01) with time, and AA synthesis was significantly (P < 0.01) greater than DHA synthesis. Conclusions: By this novel approach, we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods. By age 7 mo, LCP synthesis was dramatically lower in preterm infants fed LCPs
Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids
Background: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are long-chain polyunsaturated fatty acids (LCPs) that play pivotal roles in growth and neurodevelopment. Objective: We aimed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs. Design: Twenty-two preterm infants were randomly assigned to either the no-LCP group (fed formula without LCPs; n = 11) or the LCP group (fed formula with LCPs; n = 11). Dietary LCPs had higher 13C content than did the endogenously synthesized LCPs, which were derived from linoleic and \u3b1-linolenic acids. The 13C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1, 3, and 7 mo. Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated. Results: Percentage AA synthesis was 67.2 \ub1 7.8%, 35.9 \ub1 9.8%, and 29.0 \ub1 10.3%, and that of DHA was 41.7 \ub1 14.9%, 10.5 \ub1 8.1%, and 7.4 \ub1 6.2% at 1, 3, and 7 mo old, respectively. Absolute AA synthesis was 26.7 \ub1 4.2, 14.4 \ub1 3.9, and 11.6 \ub1 4.1mg \ub7 kg-1 \ub7 d-1 and that of DHA was 12.6 \ub1 4.5, 3.2 \ub1 2.5, and 2.3 \ub1 1.9 mg \ub7 kg-1 \ub7 d-1 at 1, 3, and 7 mo old, respectively. AA and DHA synthesis decreased significantly (P < 0.01) with time, and AA synthesis was significantly (P < 0.01) greater than DHA synthesis. Conclusions: By this novel approach, we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods. By age 7 mo, LCP synthesis was dramatically lower in preterm infants fed LCPs