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Matrix metalloproteinases correlate with alveolar-capillary permeability alteration in lung ischemia-reperfusion
P M Soccal1, Y Gasche, J C Pache
1Department of Internal Medicine, Geneva University Hospital, Switzerland.
Background:
Matrix metalloproteinases (MMPs) are able to degrade the endothelial basal lamina and increase vascular permeability.
Methods:
In a porcine model of isolated-reperfused lung, we studied the alveolar-capillary permeability and the zymographic expression of MMP-9 and MMP-2 in the bronchoalveolar lavage fluid of lungs submitted ex vivo to ischemia in three preservation solutions [modified Euro-Collins (EC), low-potassium-dextran, modified-blood]. Twenty-two pigs were randomly divided into three groups according to the preservation solution used. One lung of each pig was rapidly reperfused and analyzed (control lung) although the other lung was reperfused and analyzed after 8 hr of ischemia (ischemic lung).
Results:
Alveolar-capillary permeability, evaluated by the transferrin leak index, was increased after 8 hr of ischemia compared with controls in the three groups, but was significantly higher in the modified EC group. In the EC group, after 8 hr of ischemia, both proMMP-9 and MMP-9 increased significantly (8.8- and 22-fold, respectively) compared with controls and this increase correlated with the transferrin leak index. Neither proMMP-9 nor MMP-9 increased with the other two preservation solutions. The MMP-2 increase after ischemia was smaller and was also restricted to the EC group.
Conclusion:
MMP expression is enhanced during lung ischemia-reperfusion, especially in the presence of EC and this phenomenon correlates with the alteration of alveolar-capillary permeability.
Insights
Lung ischemia-reperfusion significantly increases matrix metalloproteinase (MMP) expression, particularly MMP-9, and alveolar-capillary permeability when using Euro-Collins preservation solution.
Area of Science:
- Cardiovascular and Respiratory System Research
- Biochemistry and Molecular Biology
Background:
- Matrix metalloproteinases (MMPs) are enzymes capable of degrading the endothelial basal lamina.
- MMPs play a role in increasing vascular permeability.
Purpose of the Study:
- To investigate the impact of different lung preservation solutions on alveolar-capillary permeability.
- To assess the expression of MMP-9 and MMP-2 in bronchoalveolar lavage fluid following lung ischemia-reperfusion.
Main Methods:
- A porcine model of isolated-reperfused lung was utilized.
- Lungs were preserved ex vivo using three solutions: modified Euro-Collins (EC), low-potassium-dextran, and modified-blood.
- Alveolar-capillary permeability and MMP expression were analyzed after 8 hours of ischemia.
Main Results:
- Alveolar-capillary permeability increased in all groups after ischemia but was significantly higher in the modified EC group.
- In the EC group, proMMP-9 and MMP-9 levels increased 8.8- and 22-fold, respectively, correlating with increased permeability.
- MMP-2 levels also showed a smaller, EC-specific increase after ischemia.
Conclusions:
- Lung ischemia-reperfusion enhances MMP expression, especially with EC preservation.
- The observed increase in MMPs, particularly MMP-9, correlates with altered alveolar-capillary permeability.