Enhanced fibrinolysis protects against lung ischemia-reperfusion injury

Christine L. Lau, Yunge Zhao, Jiyoun Kim, Irving L. Kron, Ashish Sharma, Zequan Yang, Victor E. Laubach, Joel Linden, Gorav Ailawadi, David J. Pinsky

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1241-1248
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume137
Issue number5
DOIs
StatePublished - May 2009

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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    Lau, C. L., Zhao, Y., Kim, J., Kron, I. L., Sharma, A., Yang, Z., Laubach, V. E., Linden, J., Ailawadi, G., & Pinsky, D. J. (2009). Enhanced fibrinolysis protects against lung ischemia-reperfusion injury. Journal of Thoracic and Cardiovascular Surgery, 137(5), 1241-1248. https://doi.org/10.1016/j.jtcvs.2008.12.029