The objective of these studies is to extend our understanding of the hemodynamics of the pulmonary microcirculation and lung fluid and protein flux during the transition from fetal to neonatal life. The innovative technique of lung micropuncture will be used to directly measure pressures in the subpleural microcirculation, perivascular interstitium and the alveolar liquid subphase in isolated blood perfused lungs of newborn lambs and rabbits. Regional distribution of blood flow in the lung will be measured concurrently using radiolabeled microspheres. Fluid and protein flux across the pulmonary microcirculation will be measured from the efferent duct of the caudal mediastinal lymph node in lungs of newborn lambs that are perfused in situ. First, the influence of alveolar surface tension on segmental vascular resistance and lung fluid balance will be studied in lungs of preterm lambs treated or untreated with surfactant replacement. Second, the role of eicosanoids in the regulation of pulmonary microcirculatory hemodynamics will be studied in mature and immature lambs. Specifically, the role of these mediators in the control of the circulation under basal normoxic conditions, during hypoxia and following endotoxemia will be studied. Third, the rheological factors that affect the pulmonary circulation will be investigated. As newborn infants suffer from a variety of respiratory diseases that are associated with disorders of pulmonary blood flow and abnormal accumulation of fluid and protein in the lung, knowledge derived from these studies may identify means of better treatment and possible prevention of these disorders.
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