HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Christine L. Lau Irving L. Kron Victor E. Laubach Gorav Ailawadi David J. Pinsky Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lau, C. L. Articles by Pinsky, D. J. Search for Related Content PubMed Articles by Lau, C. L. Articles by Pinsky, D. J. Related Collections Lung - transplantation Lung - basic science

J Thorac Cardiovasc Surg 2009;137:1241-1248
© 2009 The American Association for Thoracic Surgery

Cardiothoracic Transplantation

Enhanced fibrinolysis protects against lung ischemia–reperfusion injury

^a Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Va
^b Department of Pathology, Boston University, Boston, Mass
^c Department of Internal Medicine, University of Virginia, Charlottesville, Va
^d Department of Internal Medicine, Ann Arbor, Mich

Received for publication September 18, 2008; revisions received November 18, 2008; accepted for publication December 25, 2008.

^_* Address for reprints: Gorav Ailawadi, MD, PO Box 800679, Charlottesville, VA 22908-0679. (Email: GA3F{at}virginia.edu).

Objective: Ischemia–reperfusion injury continues to plague the field of lung transplantation, resulting in suboptimal outcomes. In acute lung injury, processes such as ventilator-induced injury, sepsis, or acute respiratory distress syndrome, extravascular fibrin has been shown to promote lung dysfunction and the acute inflammatory response. This study investigates the role of the fibrinolytic cascade in lung ischemia–reperfusion injury and investigates the interplay between the fibrinolytic system and the inflammatory response.

Methods: Mice lacking the plasminogen activator inhibitor-1 gene (PAI-1 knock out, PAI-1 KO; and thus increased lysis of endogenous fibrin) and wild-type mice underwent in situ left lung ischemia and reperfusion. Fibrin content in the lung was evaluated by immunoblotting. Reperfusion injury was assessed by histologic and physiologic parameters. Proinflammatory mediators were measured in bronchoalveolar lavage fluid and plasma using enzyme-linked immunosorbent assays.

Results: Ischemia–reperfusion causes fibrin deposition in murine lungs. Less fibrin was seen in PAI-1 KO mice than in wild-type mice subjected to the same ischemia–reperfusion conditions. By histologic criteria, more evidence of ischemia–reperfusion injury was noted (thickening of the interstium, cellular infiltration in the alveoli) in the wild-type than in PAI-1 KO mice. Physiologic parameters also revealed more ischemia–reperfusion injury in the wild-type than in PAI-1 KO mice. Cytokine and chemokines were elevated more in the wild-type group than the PAI-1 KO group.

Conclusions: Lung ischemia–reperfusion injury triggers fibrin deposition in the murine lungs and fibrin creates a proinflammatory environment. Preventing fibrin deposition may reduce ischemia–reperfusion injury and inflammation. This finding may lead to novel treatment strategies for ischemia–reperfusion.