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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Pathology A Study Section (PTHA)
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Ibe, B O; Raj, J U (1994) Metabolism of N-methylcarbazole by rat lung microsomes. Exp Lung Res 20:207-22
Ibe, B O; Kurantsin-Mills, J; Raj, J U et al. (1994) Plasma and urinary leukotrienes in sickle cell disease: possible role in the inflammatory process. Eur J Clin Invest 24:57-64
Filler, S G; Ibe, B O; Ibrahim, A S et al. (1994) Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis. Infect Immun 62:1064-9
Kurantsin-Mills, J; Ibe, B O; Natta, C L et al. (1994) Elevated urinary levels of thromboxane and prostacyclin metabolities in sickle cell disease reflects activated platelets in the circulation. Br J Haematol 87:580-5
Raj, J U; Kaapa, P; Anderson, J (1992) Effect of pulsatile flow on microvascular resistance in adult rabbit lungs. J Appl Physiol 72:73-81
Toga, H; Hibler, S; Ibe, B O et al. (1992) Vascular effects of platelet-activating factor in lambs: role of cyclo- and lipoxygenase. J Appl Physiol 73:2559-66
Raj, J U; Anderson, J (1992) Regional differences in interstitial fluid albumin concentration in edematous lamb lungs. J Appl Physiol 72:699-705
Raj, J U; Toga, H; Ibe, B O et al. (1992) Effects of endothelin, platelet activating factor and thromboxane A2 in ferret lungs. Respir Physiol 88:129-40
Toga, H; Ibe, B O; Raj, J U (1992) In vitro responses of ovine intrapulmonary arteries and veins to endothelin-1. Am J Physiol 263:L15-21
Raj, J U; Anderson, J (1991) Comparison of dextran and hematocrit effects in the pulmonary microcirculation. Circ Res 68:1108-16

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