Matrix Metalloproteinase Inhibition Decreases Ischemia-Reperfusion Injury after Lung Transplantation

Paola M. Soccala, Yvan Gasche, Douglas N. Miniati, Grant Hoyt, Gerald J. Berry, Ramona L. Doyle, James Theodore, Robert C. Robbins

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Increased microvascular permeability and extravasation of inflammatory cells are key events of lung ischemia-reperfusion (IR) injury. The purpose of this study was to investigate the role of matrix metalloproteinases (MMP) in IR-induced alveolar capillary membrane disruption after experimental lung transplantation. We used a rat model of lung orthotopic transplantation (n = 86) with a prolonged cold ischemic phase. MMP2 and MMP9 were elevated 4 h after the onset of ischemia and further increased during reperfusion. Compared to sham values, the alveolar-capillary membrane permeability increased by 105% and 82.6% after 4 h of ischemia and 2 h or 24 h of reperfusion, respectively. A 4- and 5-fold increase of the infiltration of ischemic tissue by neutrophils was also observed after 2 h and 24 h of reperfusion. The PO2/FIO 2 ratio dropped significantly from 244 to 76.6 after 2 h of reperfusion and from 296.4 to 127.6 after 24 h of reperfusion. A nonselective inhibitor of MMP, administered to the rats and added to the preservation solution, reduced significantly the alveolar-capillary leakage, the transmigration of neutrophils and improved gas exchanges in animals submitted to 4 h of ischemia combined with 2 h or 24 h of reperfusion. We conclude that inhibition of MMP attenuates IR injury after experimental lung transplantation.

Original languageEnglish (US)
Pages (from-to)41-50
Number of pages10
JournalAmerican Journal of Transplantation
Issue number1
StatePublished - Jan 2004
Externally publishedYes


  • Ischemia-reperfusion
  • Lung transplantation
  • MMP
  • Rat

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)


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