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dc.contributor.authorPell, Victoria R
dc.contributor.authorSpiroski, Ana-Mishel
dc.contributor.authorMulvey, John
dc.contributor.authorBurger, Nils
dc.contributor.authorCosta, Ana SH
dc.contributor.authorLogan, Angela
dc.contributor.authorGruszczyk, Anja V
dc.contributor.authorRosa, Tiziana
dc.contributor.authorJames, Andrew
dc.contributor.authorFrezza, Christian
dc.contributor.authorMurphy, Mike
dc.contributor.authorKrieg, Thomas
dc.date.accessioned2018-09-10T22:18:02Z
dc.date.available2018-09-10T22:18:02Z
dc.date.issued2018-10
dc.identifier.issn0022-2828
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280095
dc.description.abstractIschemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted and then restored, and underlies many disorders, notably myocardial infarction and stroke. While reperfusion of ischemic tissue is essential for survival, it also initiates cell death through generation of mitochondrial reactive oxygen species (ROS). Recent work has revealed a novel pathway underlying ROS production at reperfusion in vivo in which the accumulation of succinate during ischemia and its subsequent rapid oxidation at reperfusion drives ROS production at complex I by reverse electron transport (RET). Pharmacologically inhibiting ischemic succinate accumulation, or slowing succinate metabolism at reperfusion, have been shown to be cardioprotective against IR injury. Here, we determined whether ischemic preconditioning (IPC) contributes to cardioprotection by altering kinetics of succinate accumulation and oxidation during IR. Mice were subjected to a 30-minute occlusion of the left anterior descending coronary artery followed by reperfusion, with or without a protective IPC protocol prior to sustained ischemia. We found that IPC had no effect on ischemic succinate accumulation with both control and IPC mice having profound increases in succinate compared to normoxia. Furthermore, after only 1-minute reperfusion succinate was rapidly metabolised returning to near pre-ischemic levels in both groups. We conclude that IPC does not affect ischemic succinate accumulation, or its oxidation at reperfusion.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.subjectMyocardium
dc.subjectMitochondria
dc.subjectAnimals
dc.subjectMice
dc.subjectMyocardial Reperfusion Injury
dc.subjectDisease Models, Animal
dc.subjectReactive Oxygen Species
dc.subjectSuccinic Acid
dc.subjectIschemic Preconditioning, Myocardial
dc.subjectAnalysis of Variance
dc.subjectEnergy Metabolism
dc.subjectOxidation-Reduction
dc.subjectMale
dc.subjectMetabolomics
dc.subjectMetabolome
dc.titleIschemic preconditioning protects against cardiac ischemia reperfusion injury without affecting succinate accumulation or oxidation.
dc.typeArticle
prism.endingPage91
prism.publicationDate2018
prism.publicationNameJ Mol Cell Cardiol
prism.startingPage88
prism.volume123
dc.identifier.doi10.17863/CAM.27459
dcterms.dateAccepted2018-08-13
rioxxterms.versionofrecord10.1016/j.yjmcc.2018.08.010
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-10
dc.contributor.orcidSpiroski, Ana-Mishel [0000-0002-8584-8048]
dc.contributor.orcidFrezza, Christian [0000-0002-3293-7397]
dc.contributor.orcidMurphy, Mike [0000-0003-1115-9618]
dc.contributor.orcidKrieg, Thomas [0000-0002-5192-580X]
dc.identifier.eissn1095-8584
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMRC (unknown)
pubs.funder-project-idMedical Research Council (MC_UP_1002/1)
pubs.funder-project-idWellcome Trust (110159/Z/15/Z)
pubs.funder-project-idMedical Research Council (MC_U105663142)
pubs.funder-project-idMedical Research Council (MC_UU_12022/6)
pubs.funder-project-idBritish Heart Foundation (PG/15/84/31670)
rioxxterms.freetoread.startdate2019-08-14


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