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

Functional morphometry to estimate the alveolar surface area using a premature baboon model

The main respiratory pathophysiological process following premature birth is the delayed or arrested alveolar development that translates to a smaller alveolar surface area (SA). Histological morphometry is the gold standard method to measure the SA but requires invasive tissue sampling or the removal of the whole organ for analysis. Alternatively, the SA could be measured in living subjects by "functional morphometry"using Fick's first law of diffusion and noninvasive measurements of the ventilation to perfusion ratio (VA/Q). We herein aim to describe a novel functional morphometric method to measure SA using a premature baboon model. We used both functional morphometry and postmortem histological morphometry to measure SA in 11 premature baboons born at 135 days who received intensive care treatment for 14 days. For the calculation of the SA by functional morphology, we measured the septal wall thickness using microscopy, the alveolar arterial oxygen gradient using concurrent measurements of arterial pressure of O2 and CO2, and pulmonary perfusion using echocardiography and integrated Doppler signals. The median [interquartile range (IQR)] SA using functional morphometry was 3,100 (2,080-3,640) cm2 and using histological morphometry was 1,034 (634-1,210) cm2 (left lung only). The SA measured by functional morphometry was not related to the SA measured by histological morphometry. Following linear regression analysis, the V A/Q significantly predicted the histologically measured SA (R2 = 0.659, P = 0.002). In conclusion, functional measurements of ventilation to perfusion ratio could be used to estimate the alveolar surface area in prematurely born baboons and the ventilation perfusion ratio was the main determinant of the alveolar surface area. </p

Functional morphometry to estimate the alveolar surface area using a premature baboon model

The main morphological characteristic of chronic respiratory disease in prematurely born infants is the impaired/arrested alveolar growth that corresponds to a smaller aggregated alveolar surface area (SA). This decreased SA might be the limiting factor later in life affecting exercise capacity and quality of life. There is paucity of sensitive, noninvasive biomarkers to monitor the evolution of neonatal respiratory disease. Our noninvasive functional morphometric SA might help to bridge the gap between pathophysiology and clinical monitoring. </jats:p