This multidisciplinary program aims to identify mediators and mechanisms responsible for the structural remodeling of the lung's microcirculation in early pulmonary hypertension, especially the neomuscularization and loss of precapillary arterial units. Patterns of structural change vary with cause, emphasizing that pulmonary hypertension is a mixture of diseases. We focus on persistent pulmonary hypertension of the newborn as well as on four trigger events that operate at any age - hypoxia, endothelial cell injury, high flow and constriction. Identification of specific mediators and better vasodilators hold promise for better treatment. In Project I in animal models of hypertension due to hypoxia or endothelial cell injury monocrotaline), we investigate the role of inflammatory mediators including the prostanoids and platelet products in early hypertension, the role of constriction and hypoxia per se, and the 'protective' effect of vasodilators. A chronically catheterized rat model allows correlation of structural remodelling to hemodynamic derangement. In Project II we develop a guinea pig model of persistent hypertension of the newborn to mimic structural types of this syndrome we have identified in the infant, to study vasodilator response and the effect of this syndrome on subsequent vascular growth. In Project III we use methods of vascular cell and vessel organ culture to analyze intra and intercellular events of the vessel wall the the reactivity pattern of various segments of the normal and hypertensive arteries. In Project IV in selected patient groupd - A) persistent pulmonary hypertension of the newborn, B) high flow congenital heart defects, C) primar;y hypertension of infancy and childhood and D) hypoxic hypertension - sleep apnea in the adult - we will refine diagnosis of etiologic subgroups, identify responsible mechanisms and mediators, and develop better ways of treatment.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL032363-03
Application #
3106699
Study Section
(SRC)
Project Start
1983-01-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
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Reid, L M (1987) Constrictive and restrictive pulmonary hypertension in the newborn and infant. Am J Cardiovasc Pathol 1:287-99

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