PATHWAYS OF FIBRIN TURNOVER IN LAVAGE OF PREMATURE BABOONS WITH HYPEROXIC LUNG INJURY

Lung injury induced by 100% O-2 over 6 days is characterized by marked ly less alveolar fibrin and rare hyaline membranes in premature versus adult baboons. To determine the mechanism(s) underlying alveolar fibr in deposition in the evolution of hyaline membrane disease (HMD) throu gh diffuse alveolar damage (DAD) and bronchopulmonary dysplasia (BPD), we measured procoagulant and fibrinolytic activities in lung lavage o f premature baboons with HMD, those treated with 100% O-2 for 6 days ( DAD) or for 7 days followed by 14 days 80% O-2 (BPD). Lavage procoagul ant activity, mainly due to tissue factor associated with Factor VII, was increased by hyperoxia. Plasminogen-dependent fibrinolytic activit y, 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 evol ving DAD or BPD. Antiplasmin activity was stable or decreased. Althoug h plasminogen was undetectable in lavage, D-dimer was increased in lav age of the groups exposed to hyperoxia versus HMD. The defect in plasm inogen activator activity in lavage fluids of adult baboons with DAD i nduced by O-2 does not occur in premature baboons with HMD, evolving D AD, or BPD Expression of fibrinolytic activity in the lower respirator y tract of premature baboons is dependent on local access to plasminog en, which is present in relatively low concentrations in plasma of the se animals.