The general aims of this project are to define: 1) the role of vasoactive substances in the physiological and pharmacological control of the pulmonary circulation; and 2) the factors involved in regulating the formation and reabsorption of lung liquid in fetal lambs. An isolated (in-situ), pump perfused, lower left lung preparation in anesthetized, exteriorized fetal sheep will be used to study regulation of blood flow to the lungs. Acute studies will consider the interaction of non-eicosanoid vasoactive substances and metabolites of the arachidonic acid cascade on the pulmonary circulation. Evaluation will be made of the role of leukotrienes in modulating the normally high fetal pulmonary vascular tone. Acute studies will be carried out to measure the permeability of pulmonary epithelium to leukotrienes and to quantify production of leukotrienes in fetal lung liquid, lymph and blood during and following prolonged hypoxia. Also the interaction of the thyroid gland, AVP and epinephrine in lung liquid secretion and reabsorption in the near term fetus will be evaluated. The long-term objectives of these studies are to provide a better understanding of the factors which contribute to: 1) regulation of the pulmonary circulation, and 2) adaptations which must occur in the transition from liquid to air breathing at birth. Knowledge of normal and altered mechanisms of control of the pulmonary circulation and lung liquid formation, should be of considerable clinical value in understanding disturbances which may occur in the pulmonary circulation during the perinatal period.
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