Lung ischemia-reperfusion injury (LIRI) is one of the leading causes of primary graft dysfunction, which limits graft survival in lung transplant recipients. To date, there is no specific therapeutic intervention for LIRI. In other models, autoimmunity to the N2 epitope of the heavy chain of non-muscle myosin has been shown to be an important mechanism underlying the inflammatory response to reperfusion injury. The objective of our study is to see whether a novel mimeotopic peptide that blocks activation of the N2 pathway can mitigate LIRI in miniature swine, a pre-clinical large-animal model. Four miniature swine underwent 2 or 4 hours of left lung ischemia. Prior to reperfusion, animals were treated with either the N2 peptide or normal saline (NS). Serial open lung biopsies and blood sampling were performed throughout a 24-hour period of reperfusion. Serum was analyzed for biomarkers of acute lung injury (IFN-gamma, CXCL-10, MCP-1) and tissue biopsies analyzed by a pathologist blinded to the intervention. After 4 hours of ischemia, N2-treated swine demonstrated significantly decreased alveolar and interstitial edema compared to NS-treated swine at 6, 12, and 18 hours of reperfusion. N2 peptide also decreased levels of IFN-gamma and MCP-1 during the reperfusion period. Two hours of ischemia were not sufficient to demonstrate differences between the treatment and control animals. This preliminary study demonstrates that blocking the N2 pathway in a pre-clinical model of LIRI decreases the inflammatory response and tissue injury. Further investigation is needed to characterize the role of N2 pathway blockade in this and other models of ischemia-reperfusion injury.
Gottschall, J.: Grant/Research Support, Decimmune. Haas, M.: Employee, Decimmune.
To cite this abstract in AMA style:Madariaga M, Sihag S, Gottschall J, Farkash E, Haas M, Carroll M, Allan J. Mitigating Lung Ischemia-Reperfusion Injury in Miniature Swine [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/mitigating-lung-ischemia-reperfusion-injury-in-miniature-swine/. Accessed October 23, 2020.
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