Abstract
Ischemia-reperfusion injury is a major factor in the early phase of lung transplantation. We hypothesized that aprotinin, a nonspecific serine protease inhibitor, attenuates ischemia-reperfusion lung injury by inhibiting the inflammatory response and suppressing NADPH oxidase. We used an isolated rat lung model to test the above. A Control group was immediately perfused with fresh heparinized allogeneic blood after lung harvest without an ischemic period. Study lungs were flushed with low-potassium dextran (LPD) solution and stored for 18h at 4 degrees C then divided into two groups: the LPD group was flushed with LPD solution only, and the LPD+A group was flushed with LPD solution +200KIU/ml aprotinin. Lungs in all three groups were then reperfused with fresh heparinized allogeneic blood for 120min at 37 degrees C. Throughout reperfusion, PO(2) levels in the LPD+A group were similar to those in the Control group; although in the LPD group, PO(2) levels were significantly lower (P<0.05). Tissue MDA levels were significantly higher in the LPD group than the Control and LPD+A groups (P<0.05). IL-8 levels were significantly higher in the LPD group than the Control group (P<0.05), while in the LPD+A group they were similar to those in the Control group. Histological evaluation showed interstitial edema accompanied by neutrophil extravasation in the LPD group, whereas this effect was modest in the LPD+A group. An additional study of ischemia-reperfusion in an alveolar macrophage culture showed that the activitvation of NADPH oxidase, and translocation of p47(phox) from the cytosol to the membrane were suppressed in aprotinin group. Aprotinin attenuates ischemia-reperfusion lung injury by inhibiting the early inflammatory response, neutrophil extravasation and the production of oxygen free radicals through inhibition of the activation of the NADPH oxidase. The inhibition of p47(phox) translocation in alveolar macrophage seemed involved in this mechanism of aprotinin.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.