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Am J Physiol Lung Cell Mol Physiol. 2009 Mar;296(3):L277-85. doi: 10.1152/ajplung.90475.2008. Epub 2008 Dec 5.

Neither fibrin nor plasminogen activator inhibitor-1 deficiency protects lung function in a mouse model of acute lung injury.

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1
School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan.

Abstract

Fibrin impairs surfactant function in vitro, and inhibition of fibrinolysis by plasminogen activator inhibitor (PAI-1) is thought to promote fibrin accumulation in acute lung injury (ALI). This has led to speculation that impaired PAI-1 and fibrin accumulation should protect lung function in ALI. We tested this hypothesis by investigating ALI severity in fibrinogen-deficient (Fgn-/-) and PAI-1-deficient (PAI-1-/-) mice. PAI-1-/-, C57BL/6, Fgn-/-, and Fgn+/- females were anesthetized and allowed to aspirate 4 microl/g of hydrochloric acid (pH 1.0) and then reanesthetized and connected to a ventilator 48 h later. Naive C57BL/6 and Fgn+/- females served as controls. Following deep inflation (DI), forced oscillations were delivered periodically over 8 min to measure changes in elastance (H) as a surrogate of lung derecruitment, at positive end-expiratory pressures (PEEP) of 6, 3, and 1 cmH(2)O. Increases in H following DI in acid-injured mice were greater than naive strain-matched controls. Increases in H were no different between injured PAI-1-/- and C57BL/6, or between injured Fgn-/- and +/- mice, at any PEEP. Pressure-volume curves were no different between injured groups. Total lung fibrin was lower in injured PAI-1-/- and Fgn-/- mice relative to injured C57BL/6 and Fgn+/- mice, respectively, but indices of permeability were no different between strains. Unexpectedly, neither fibrin nor PAI-1 deficiency protects lung mechanical function in mice with acid-induced ALI. We speculate that in vivo lung function may be more closely tied to permeability and alveolar protein in general, rather than being linked specifically to fibrin.

Comment in

PMID:
19060228
PMCID:
PMC2660214
DOI:
10.1152/ajplung.90475.2008
[Indexed for MEDLINE]
Free PMC Article

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