The overall goal of this program project is to study specific pathophysiologic mechanisms underlying common neonatal lung disorders. The response of the immature or developing lung to acute injury and reparative phenomenon will be studied utilizing animal models of disease. The program consists of four projects and two cores and will bring together a large number of investigators with expertise in several disciplines to focus on mechanisms of lung damage in repair. The long range goal is to improve current methods of treatment and prevention of HMD and improve methods of treatment in other common lung disorders in order to prevent the common complication of bronchopulmonary dysplasia, a disorder of premature infants with catastrophic consequences. This program project will extend the studies currently funded through the pulmonary SCOR program. The projects focus on four main objectives: 1. to understand the mechanisms of sequential lung injury in hyaline membrane disease (HMD) and mechanisms of normal and abnormal recovery (Project 1), 2. to study mechanisms of pulmonary host defenses in the neonate, including cellular immunology and organ response to infection (Projects 2 and 3), 3. to investigate mechanisms controlling the pulmonary circulation in the neonate and factors regulating gas exchange during acute and convalescent stages of lung injury (Projects 1 and 3), 4. to define features unique to the neonate in the development of respiratory failure and the physiologic handicaps of the neonate in responding to respiratory failure. The combined projects share common goals and depend upon common use of core animal, physiologic, biochemistry and electron microscopic facilities and support personnel within the Administrative and Research Resources Core.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL039157-05
Application #
3098634
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1987-07-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1993-06-30
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Murphy, T D; Gibson, R L; Standaert, T A et al. (1995) Diaphragmatic failure during group B streptococcal sepsis in piglets: the role of thromboxane A2. J Appl Physiol 78:491-8
Ruzinski, J T; Skerrett, S J; Chi, E Y et al. (1995) Deposition of particles in the lungs of infant and adult rats after direct intratracheal administration. Lab Anim Sci 45:205-10
Martin, T R; Ruzinski, J T; Wilson, C B et al. (1995) Effects of endotoxin in the lungs of neonatal rats: age-dependent impairment of the inflammatory response. J Infect Dis 171:134-44
Beaty, C D; Franklin, T L; Uehara, Y et al. (1994) Lipopolysaccharide-induced cytokine production in human monocytes: role of tyrosine phosphorylation in transmembrane signal transduction. Eur J Immunol 24:1278-84
Gibson, R L; Berger, J I; Redding, G J et al. (1994) Effect of nitric oxide synthase inhibition during group B streptococcal sepsis in neonatal piglets. Pediatr Res 36:776-83
Jackson, J C; Standaert, T A; Truog, W E et al. (1994) Full-tidal liquid ventilation with perfluorocarbon for prevention of lung injury in newborn non-human primates. Artif Cells Blood Substit Immobil Biotechnol 22:1121-32
Juul, S E; Kinsella, M G; Jackson, J C et al. (1994) Changes in hyaluronan deposition during early respiratory distress syndrome in premature monkeys. Pediatr Res 35:238-43
Jackson, J C; Truog, W E; Standaert, T A et al. (1994) Reduction in lung injury after combined surfactant and high-frequency ventilation. Am J Respir Crit Care Med 150:534-9
Juul, S E; Kinsella, M G; Wight, T N et al. (1993) Alterations in nonhuman primate (M. nemestrina) lung proteoglycans during normal development and acute hyaline membrane disease. Am J Respir Cell Mol Biol 8:299-310
Gibson, R L; Davis, C B; Standaert, T A et al. (1993) Lung vascular responses and VA/Q matching after chronic hypoxia in neonatal piglets. J Dev Physiol 19:157-63

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