Severe growth retardation is one of the most serious effects of protein-calorie malnutrition (PCM) in young animals and children. This retardation is currently thought to be irreversible if the malnutrition occurs during a period of rapid cell division rather than during cell enlargement. However, these generalities have not been examined for organ systems in ways that could indicate whether structure and function are retarded in-parallel. This proposal seeks to determine the magnitude and reversibility of damage done to the growing lung during a period of perinatal PCM, preceded and follwed by access to a nutritionally adequate diet. Pulmonary development will be monitored in fetal and postnatal guinea pigs, whose mothers have been maintained for 3 weeks during pregnancy or lactation on diets designed to induce the human equivalents of normal growth, protein deficiency (kwashiorkor), and caloric deficiency (marasmus). For up to 24 weeks of age, the lungs of offspring from these malnourished mothers will be assessed in 3 major areas of concern. First, the compliance of the lungs will be measured as volume changes under different transpulmonary pressures of air and saline. By thus determining surface tension and tissue elastic recoil properties, the effects of PCM can be equated with the depletion sizes of lung cells will be measured to determine the permanent effect of PCM on the total size of the cell population. Of particular concern here will be the contents of deoxyribonucleic acids and proteins in lung cells. Third, lung ultrastructure will be examined with light and electron microscopy, to determine total aleolar surface are and the harmonic barrier thickness to gas diffusion. Seen microscopically, PCM appears to cause irreversible damage to the terminal alveolar units in a manner analogous to emphysema. Thus, this study will establish the acute and long term effects of perinatal malnutrition on lung development, with repercussions reaching into the animal's adult life.
