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. 1989 Aug;135(2):387–399.

Abnormalities of pathways of fibrin turnover in lung lavage of rats with oleic acid and bleomycin-induced lung injury support alveolar fibrin deposition.

S Idell 1, K K James 1, C Gillies 1, D S Fair 1, R S Thrall 1
PMCID: PMC1879916  PMID: 2476934

Abstract

Alveolar fibrin deposition commonly accompanies acute lung injury, but the nature of the local abnormalities of coagulation and fibrinolysis that support pathologic fibrin deposition are not well understood. The trended abnormalities of procoagulant and fibrinolytic activities occurring in lung lavage fluids of Fischer 344 rats after lung injury induced by intravenous oleic acid (OA) or intratracheal bleomycin were studied. After injury by either agent, bronchoalveolar lavage (BAL) contained increased procoagulant activity and decreased fibrinolytic activity. Lavage procoagulant activity was mainly due to an activator of Factor X attributable to the extrinsic coagulation pathway, and fibrinolytic activity was almost completely plasminogen dependent. Major mechanisms of inhibition of fibrinolytic activity involved both the inhibition of the plasminogen activator (PA) and plasmin. These abnormalities were temporally associated with prominent alveolar fibrin deposition in both models. In OA-treated animals, lavage fibrinolytic activity was absent or profoundly decreased, and antiplasmin and procoagulant activities were increased within 4 hours after the induction of acute lung injury. By 24 hours after OA, lavage PA inhibitor (PAI) activity was elevated with sustained antiplasmin activity. By 3 days after OA, these abnormalities had resolved in association with almost complete resolution of alveolar fibrin deposits. Within 3 days after bleomycin-induced lung injury, lavage procoagulant activity was increased and fibrinolytic activity was depressed due to increased antiplasmin and PAI activities. These conditions persisted for 2 weeks, during which time alveolar fibrin deposition was associated with the development of pulmonary fibrosis. These data indicate that a disruption of the normal balance between procoagulant and fibrinolytic activities occurs in alveolar lining fluids of rats with alveolitis induced by either OA or bleomycin, and that concurrent abnormalities of pathways of fibrin turnover that occur in alveolar lining fluids promote the alveolar fibrin deposition associated with these lung injuries.

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Selected References

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