Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease.
Nitric oxide (NO) serves multiple functions in the developing lung, and pulmonary NO production is decreased in a baboon model of chronic lung disease (CLD) after premature birth at 125 days (d) gestation (term = 185d). To determine whether postnatal NO administration alters the genesis of CLD, the effects of inhaled NO (iNO, 5 ppm) were assessed in the baboon model over 14d. iNO caused a decrease in pulmonary artery pressure in the first 2d and a greater rate of spontaneous closure of the ductus arteriosus, and lung compliance was greater and expiratory resistance was improved during the first week. With iNO, postmortem pressure-volume curves were shifted upward, lung DNA content and cell proliferation were increased, and lung growth was preserved to equal that which occurs during the same period in utero. In addition, the excessive elastin deposition characteristic of CLD was normalized by iNO, and there was evidence of stimulation of secondary crest development. Thus, in the baboon model of CLD, iNO improves early pulmonary function and alters lung growth and extracellular matrix deposition. As such, NO biosynthetic pathway dysfunction may contribute to the pathogenesis of CLD.
McCurnin
Donald C
DC
Department of Pediatrics, University of Texas Health Science Center, San Antonio, Texas, USA.
Pierce
Richard A
RA
Chang
Ling Yi
LY
Gibson
Linda L
LL
Osborne-Lawrence
Sherri
S
Yoder
Bradley A
BA
Kerecman
Jay D
JD
Albertine
Kurt H
KH
Winter
Vicki T
VT
Coalson
Jacqueline J
JJ
Crapo
James D
JD
Grubb
Peter H
PH
Shaul
Philip W
PW
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002908:Chronic Disease; D004549:Elastin / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000254:growth & development / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008171:Lung Diseases / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010215:Papio; D011650:Pulmonary Alveoli / Q000473:pathology; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects
D001993:Bronchodilator Agents; D009569:Nitric Oxide; D004549:Elastin