Show simple item record

dc.contributor.authorHack, Benjaminen_US
dc.contributor.authorWitting, Paulen_US
dc.contributor.authorS. Rayner, Benjaminen_US
dc.contributor.authorStocker, Rolanden_US
dc.contributor.authorHeadrick, Johnen_US
dc.contributor.editorNaranjan S Dhallaen_US
dc.description.abstractDespite the general understanding that ischemia-reperfusion (I/R) promotes oxidant stress, specific contributions of oxidant stress or damage to myocardial I/R injury remain poorly defined. Moreover, whether endogenous 'cardioprotectants' such as adenosine act via limiting this oxidant injury is unclear. Herein we characterized effects of 20 min ischemia and 45 min reperfusion on cardiovascular function, oxidative stress and damage in isolated perfused mouse hearts (with glucose or pyruvate as substrate), and examined whether 10 占adenosine modified these processes. In glucose-perfused hearts post-ischemic contractile function was markedly impaired (< 50% of pre-ischemia), cell damage assessed by lactate dehydrogenase (LDH) release was increased (12 ᠲ IU/g vs. 0.2 ᠰ.1 IU/g in normoxic hearts), endothelial-dependent dilation in response to ADP was impaired while endothelial-independent dilation in response to nitroprusside was unaltered. Myocardial oxidative stress increased significantly, based on decreased glutathione redox status ([GSSG]/[GSG + GSSH] = 7.8 ᠰ.3% vs. 1.3 ᠰ.1% in normoxic hearts). Tissue cholesterol, native cholesteryl esters (CE) and the lipid-soluble antioxidant a-tocopherol (a-TOH, the most biologically active form of vitamin E) were unaffected by I/R, whereas markers of primary lipid peroxidation (CE-derived lipid hydroperoxides and hydroxides; CE-O(O)H) increased significantly (14 ᠲ vs. 2 ᠱ pmol/mg in normoxic hearts). Myocardial a -tocopherylquinone (a-TQ; an oxidation product of a -TOH) also increased (10.3 ᠱ.0 vs. 1.7 ᠰ.2 pmol/mg in normoxic hearts). Adenosine treatment improved functional recovery and vascular function, and limited LDH efflux. These effects were associated with an anti-oxidant effect of adenosine, as judged by inhibition of I/R-mediated changes in glutathione redox status (by 60%), a-TQ (80%) and CE-O(O)H (100%). Provision of 10 mM pyruvate as sole substrate (to by-pass glycolysis) modestly reduced I/R injury and changes in glutathione redox status and a-TQ, but not CE-O(O)H. Adenosine exerted further protection and anti-oxidant actions in these hearts. Functional recoveries and LDH efflux correlated inversely with oxidative stress and a -TQ (but not CE-O(O)H) levels. Collectively, our data reveal selective oxidative events in post-ischemic murine hearts, which are effectively limited by adenosine (independent of substrate). Correlation of post-ischemic cardiovascular outcomes with specific oxidative events (glutathione redox state, a-TQ) supports an important anti-oxidant component to adenosinergic protection.en_US
dc.publisherSpringer Science + Business Mediaen_US
dc.publisher.placeBerlin, Germanyen_US
dc.relation.ispartofjournalMolecular and Cellular Biochemistryen_US
dc.titleOxidant Stress and Damage in Post-Ischemic Mouse Hearts: Effects of Adenosineen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyGriffith Health, School of Medical Scienceen_US
gro.hasfulltextNo Full Text

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record