The mitochondria-targeted anti-oxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model.

TitleThe mitochondria-targeted anti-oxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model.
Publication TypeJournal Article
Year of Publication2015
AuthorsDare, AJ, Logan, A, Prime, TA, Rogatti, S, Goddard, M, Bolton, EM, J Bradley, A, Pettigrew, GJ, Murphy, MP, Saeb-Parsy, K
JournalJ Heart Lung Transplant
Volume34
Issue11
Pagination1471-80
Date Published2015 Nov
ISSN1557-3117
KeywordsAnimals, Antioxidants, Disease Models, Animal, Female, Free Radical Scavengers, Heart Transplantation, Male, Mice, Mice, Inbred C57BL, Micronutrients, Mitochondria, Heart, Organ Preservation, Organophosphorus Compounds, Oxidative Stress, Primary Graft Dysfunction, Rats, Rats, Wistar, Reactive Oxygen Species, Reperfusion Injury, Ubiquinone
Abstract

BACKGROUND: Free radical production and mitochondrial dysfunction during cardiac graft reperfusion is a major factor in post-transplant ischemia-reperfusion (IR) injury, an important underlying cause of primary graft dysfunction. We therefore assessed the efficacy of the mitochondria-targeted anti-oxidant MitoQ in reducing IR injury in a murine heterotopic cardiac transplant model.METHODS: Hearts from C57BL/6 donor mice were flushed with storage solution alone, solution containing the anti-oxidant MitoQ, or solution containing the non-anti-oxidant decyltriphenylphosphonium control and exposed to short (30 minutes) or prolonged (4 hour) cold preservation before transplantation. Grafts were transplanted into C57BL/6 recipients and analyzed for mitochondrial reactive oxygen species production, oxidative damage, serum troponin, beating score, and inflammatory markers 120 minutes or 24 hours post-transplant.RESULTS: MitoQ was taken up by the heart during cold storage. Prolonged cold preservation of donor hearts before IR increased IR injury (troponin I, beating score) and mitochondrial reactive oxygen species, mitochondrial DNA damage, protein carbonyls, and pro-inflammatory cytokine release 24 hours after transplant. Administration of MitoQ to the donor heart in the storage solution protected against this IR injury by blocking graft oxidative damage and dampening the early pro-inflammatory response in the recipient.CONCLUSIONS: IR after heart transplantation results in mitochondrial oxidative damage that is potentiated by cold ischemia. Supplementing donor graft perfusion with the anti-oxidant MitoQ before transplantation should be studied further to reduce IR-related free radical production, the innate immune response to IR injury, and subsequent donor cardiac injury.

DOI10.1016/j.healun.2015.05.007
Alternate JournalJ. Heart Lung Transplant.
Citation Key10.1016/j.healun.2015.05.007
PubMed ID26140808
PubMed Central IDPMC4626443
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom