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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL041387-03
Application #
3359170
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1990-07-01
Project End
1994-08-31
Budget Start
1992-09-01
Budget End
1994-08-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Roberts Jr, J D; Fineman, J R; Morin 3rd, F C et al. (1997) Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group. N Engl J Med 336:605-10
Shaul, P W; Yuhanna, I S; German, Z et al. (1997) Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension. Am J Physiol 272:L1005-12
Steinhorn, R H; Russell, J A; Morin 3rd, F C (1995) Disruption of cGMP production in pulmonary arteries isolated from fetal lambs with pulmonary hypertension. Am J Physiol 268:H1483-9
Morin 3rd, F C; Stenmark, K R (1995) Persistent pulmonary hypertension of the newborn. Am J Respir Crit Care Med 151:2010-32
Leach, C L; Holm, B; Morin 3rd, F C et al. (1995) Partial liquid ventilation in premature lambs with respiratory distress syndrome: efficacy and compatibility with exogenous surfactant. J Pediatr 126:412-20
Thusu, K G; Morin 3rd, F C; Russell, J A et al. (1995) The cGMP phosphodiesterase inhibitor zaprinast enhances the effect of nitric oxide. Am J Respir Crit Care Med 152:1605-10
Steinhorn, R H; Morin 3rd, F C; Van Wylen, D G et al. (1994) Endothelium-dependent relaxations to adenosine in juvenile rabbit pulmonary arteries and veins. Am J Physiol 266:H2001-6
Iwamoto, J; Krasney, J A; Morin 3rd, F C (1994) Methemoglobin production by nitric oxide in fresh sheep blood. Respir Physiol 96:273-83
Fineman, J R; Wong, J; Morin 3rd, F C et al. (1994) Chronic nitric oxide inhibition in utero produces persistent pulmonary hypertension in newborn lambs. J Clin Invest 93:2675-83
Wilcox, D T; Glick, P L; Karamanoukian, H et al. (1994) Pathophysiology of congenital diaphragmatic hernia. V. Effect of exogenous surfactant therapy on gas exchange and lung mechanics in the lamb congenital diaphragmatic hernia model. J Pediatr 124:289-93

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