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Role of Fibrin in Determining Airway Closure^*

^* From the Vermont Lung Center, University of Vermont, Burlington, VT.

Correspondence to: Scott Wagers, MD, Rm 226, 149 Beaumont Ave, Burlington, VT 05405-0075; e-mail: scott.wagers{at}uvm.edu

Airway fibrin deposition occurs in inflammatory disorders of the lung, and it is known that fibrin inhibits surfactant function. The pressure-volume (PV) curves of asthmatic patients are widened, and this is thought to be due to an enhancement of airway closure. Tissue plasminogen activator (tPA) is a fibrinolytic agent that works through the activation of plasminogen in the presence of fibrin. We sought to determine whether lysis of airway fibrin would diminish the PV curve widening that is seen in airway inflammation.

The PV curves of Balb/c mice with inflamed airways induced by sensitization with intraperitoneal ovalbumin that were challenged with aerosolized ovalbumin (ova/ova) were compared to mice that received no treatment (controls). Mice underwent nebulization with saline solution, tPA, or fibrinogen followed by thrombin (fibrin), and static PV curves were measured by using a computer-controlled ventilator (flexiVent; SCIREQ; Montreal, QC, Canada) every 10 min for a total of 40 min. The PV curve area was determined, and the percentage change from baseline was calculated at each time point.

Forty minutes after undergoing nebulization, the values for the percentage change from baseline were as follows: control mice with nebulization (three mice), 52%; ova/ova mice that had received saline solution nebulization (five mice), 183%; ova/ova mice that had received tPA nebulization (seven mice), 82%; and control mice that had received fibrin nebulization (four mice), 135%. The change in the PV curve area was largely accounted for by changes in the inspiratory limb of the PV curve.

We have demonstrated that mice with inflamed airways have more PV curve widening, which can be diminished by the administration of tPA and is emulated by the administration of nebulized fibrin. On the basis of these functional results, we concluded that fibrin deposition is a significant determinant of the enhanced airway closure observed in inflamed lungs.

	Footnotes

 
Abbreviations: PV = pressure-volume; tPA = tissue plasminogen activator

This Article Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wagers, S. Articles by Irvin, C. G. Search for Related Content PubMed PubMed Citation Articles by Wagers, S. Articles by Irvin, C. G.