• J. Thorac. Cardiovasc. Surg. · Jan 2020

    Impact of triptolide during ex vivo lung perfusion on grafts after transplantation in a rat model.

    • Sarah Burki, Kentaro Noda, Brian J Philips, Murugesan Velayutham, Sruti Shiva, Pablo G Sanchez, Ajay Kumar, and Jonathan D'Cunha.
    • Division of Lung Transplant and Lung Failure, Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa.
    • J. Thorac. Cardiovasc. Surg. 2020 Jan 23.

    ObjectiveEx vivo lung perfusion creates a proinflammatory environment leading to deterioration in graft quality that may contribute to post-transplant graft dysfunction. Triptolide has been shown to have a therapeutic potential in various disease states because of its anti-inflammatory properties. On this basis, we investigated the impact of triptolide on graft preservation during ex vivo lung perfusion and associated post-transplant outcomes in a rat transplant model.MethodsWe performed rat normothermic ex vivo lung perfusion with acellular Steen solution containing 100 nM triptolide for 4 hours and compared the data with untreated lungs. Orthotopic single lung transplantation after ex vivo lung perfusion was performed.ResultsPhysiologic and functional parameters of lung grafts on ex vivo lung perfusion with triptolide were better than those without treatment. Graft glucose consumption was significantly attenuated on ex vivo lung perfusion with triptolide via inhibition of hypoxia signaling resulting in improved mitochondrial function and reduced oxidative stress. Also, intragraft inflammation was markedly lower in triptolide-treated lungs because of inhibition of nuclear factor-κB signaling. Furthermore, post-transplant graft function and inflammatory events were significantly improved in the triptolide group compared with the untreated group.ConclusionsTreatment of lung grafts with triptolide during ex vivo lung perfusion may serve to enhance graft preservation and improve graft protection resulting in better post-transplant outcomes.Copyright © 2020. Published by Elsevier Inc.

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