and/or aims): At birth pulmonary blood flow increases and pulmonary arterial pressure and vascular resistance decrease dramatically. In a syndrome in which this transition is incomplete, persistent pulmonary hypertension of the newborn, there is persistent pulmonary hypertension at birth and a high mortality rate. Newborns who die from this syndrome have muscularization of the intra-acinar pulmonary arteries. In the adult pulmonary circulation, chronically increasing pressure by increasing flow, remodels vessels and produces sus-tained pulmonary hypertension. The applicant has shown that ligating the ductus arteriosus several days before birth, increases pressure and flow in the fetal pulmonary circulation, causing muscularization of intra-acinar arteries, and pulmonary hypertension at birth. In an experimental animal preparation, the applicant will determine whether pulmonary hypertension is due to: (1) an excess of vasoconstrictor leukotrienes (LT), (2) a deficit of the vasodilator prostacyclin, or (3) altered interaction of pulmonary vascular endothelium and smooth muscle. These hypotheses will be tested by analysis of the hemodynamic response of the pulmonary circulation in lambs with and without pulmonary hypertension, measurement of eicosanoid concentrations in body fluids, and measurement of the response of blood vessels isolated from lamb lungs.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Respiratory and Applied Physiology Study Section (RAP)
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State University of New York at Buffalo
Schools of Medicine
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