Pathways of fibrin turnover in lavage of premature baboons with hyperoxic lung injury.
Lung injury induced by 100% O2 over 6 days is characterized by markedly less alveolar fibrin and rare hyaline membranes in premature versus adult baboons. To determine the mechanism(s) underlying alveolar fibrin deposition in the evolution of hyaline membrane disease (HMD) through diffuse alveolar damage (DAD) and bronchopulmonary dysplasia (BPD), we measured procoagulant and fibrinolytic activities in lung lavage of premature baboons with HMD, those treated with 100% O2 for 6 days (DAD) or for 7 days followed by 14 days 80% O2 (BPD). Lavage procoagulant activity, mainly due to tissue factor associated with Factor VII, was increased by hyperoxia. Plasminogen-dependent fibrinolytic activity, due to both tissue plasminogen activator and urokinase, was stable or increased after hyperoxia. Plasminogen activator inhibitor 1 (PAI-1) was detectable in lavage of animals with HMD but not those with evolving DAD or BPD. Antiplasmin activity was stable or decreased. Although plasminogen was undetectable in lavage, D-dimer was increased in lavage of the groups exposed to hyperoxia versus HMD. The defect in plasminogen activator activity in lavage fluids of adult baboons with DAD induced by O2 does not occur in premature baboons with HMD, evolving DAD, or BPD. Expression of fibrinolytic activity in the lower respiratory tract of premature baboons is dependent on local access to plasminogen, which is present in relatively low concentrations in plasma of these animals.
Idell
S
S
Department of Medicine, University of Texas Health Science Center, Tyler 75710.
Kumar
A
A
Koenig
K B
KB
Coalson
J J
JJ
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D005167:Factor VII / Q000032:analysis; D005337:Fibrin / Q000032:analysis* / Q000378:metabolism*; D005342:Fibrinolysis; D006801:Humans; D006819:Hyaline Membrane Disease / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D007231:Infant, Newborn; D008297:Male; D010100:Oxygen; D010215:Papio; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D012121:Respiration, Artificial / Q000009:adverse effects; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D017395:Plasminogen Activator Inhibitor 1; D005167:Factor VII; D005337:Fibrin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D010100:Oxygen