Recent evidence has indicated that the fetal lung is critically impaired by intrauterine ethanol exposure. Thus, retarded lung growth and development may contribute to the higher perinatal mortality and morbidity, as well as the increased susceptibility to respiratory infections, which occur following fetal alcohol exposure, including the Fetal Alcohol Syndrome (FAS). Through the ADAMHA Small Grant Program, the time-dated pregnant guinea pig would be developed as a model of such stress, in a species which is normally born with an advanced pulmonary system compared to other rodents. Pregnant guinea pigs would receive 2 or 4 g ethanol/day/kg maternal weight during their last trimester (from day 45 post-insemination until term), administered by intragastric intubation with appropriate pair-fed, pair-intubated controls. Newborn guinea pigs will be studied either within 6 hours of birth or as juveniles following ad libitum refeeding without alcohol. Functional lung maturity will be assessed in vivo by measuring metabolic performance and ventilatory volumes, hypoxic ventilatory drive, and pulmonary compliance. The morphological and biochemical development of their lungs would be evaluated by means of fresh and dry weights, DNA and structural protein contents, lavage and tissue surfactant contents, and the morphometric description of lung cell types, elastin deposition, and the anatomically-estimated pulmonary diffusing capacity using light and electron microscopy. Hematological profiles and relative indices of growth retardation in the hearts, livers, and adrenals of the animals will also be obtained. This proposal will provide previously unavailable information directly bearing on the health and survivability of children with FAS, as well as the larger population of infants showing more subtle fetal alcohol effects. Future studies would then proceed with a more detailed examination of the intrauterine time course of any ethanol-induced lung damage, and characterization of the intrauterine environment of the growing lung, for example ethanol-induced changes in placental diffusing capacity and endogenous hormone levels.
