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Matrix metalloproteinase inhibition decreases ischemia-reperfusion injury after lung transplantation.

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  • 1. Division of Pulmonary & Critical Care Medicine, Department of Medicine, Stanford University Medical Center, Stanford, CA, USA.
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    • Soccal PM 1
    (1 author)

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American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 01 Jan 2004, 4(1):41-50
https://doi.org/10.1046/j.1600-6135.2003.00277.x PMID: 14678033 

Abstract 

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/FIO2 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.

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