Mechanisms for Reduced Total Lung Capacity at Birth and during Hyaline Membrane Disease in Premature Newborn Monkeys

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Abstract
To determine whether the cause of reduced total lung capacity (TLC) in hyaline membrane disease (HMD) is due to alveolar collapse, alveolar edema, or both, TLC was measured by N2-washout in premature Macaca nemestrina monkeys during the first 3 h of life. The TLC of animals with HMD was only one-third that of healthy premature monkeys over the first 3 h of life (p < 0.01). At 3.5 h, lung tissue was rapidly frozen in situ during lung inflation to TLC. Samples of frozen lung tissue were freeze dried, embedded, sectioned, and examined by point counting. Animals with HMD had alveolar saccules filled with the residue of proteinaceous fluid, but little alveolar collapse was noted. The proportion of points falling on empty alveolar spaces was 74% in the healthy animals but only 18% in animals with HMD (p < 0.01); there was a 70-fold incrase in the residue present in alveoli of animals with HMD (p < 0.05). In a separate experiment, rapid serial measurements of TLC by N2-washout showed that healthy premature monkeys, but not those with HMD, have a steady increase in TLC during the first few minutes of life, presumably due to clearance of lung liquid. Although the initial cause of reduced TLC in HMD appears to be inadequate clearance of fetal lung liquid, by 3 h of age proteinaceous alveolar edema is primarily responsible.