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dc.contributor.authordu Toit, Een_US
dc.contributor.authorGenis, Aen_US
dc.contributor.authorOpie, Len_US
dc.contributor.authorPollesello, Pen_US
dc.contributor.authorLochner, Aen_US
dc.date.accessioned2017-05-03T16:58:55Z
dc.date.available2017-05-03T16:58:55Z
dc.date.issued2008en_US
dc.date.modified2011-11-03T06:15:51Z
dc.identifier.issn0007-1188en_US
dc.identifier.doi10.1038/bjp.2008.52en_AU
dc.identifier.urihttp://hdl.handle.net/10072/25669
dc.description.abstractBackground and purpose: Myocardial reperfusion injury prevents optimal salvage of the ischaemic myocardium, and adjunct therapy that would significantly reduce reperfusion injury is still lacking. We investigated whether (1) the heart could be pre- and/or post-conditioned using levosimendan (levosimendan pre-conditioning (LPC) and levosimendan post-conditioning (LPostC)) and (2) the prosurvival kinases and/or the sarcolemmal or mitochondrial KATP channels are involved. Experimental approach: Isolated guinea pig hearts were treated with two 5 min cycles of levosimendan (0.1 卩 interspersed with vehicle perfusion, or two 5 min cycles of ischaemia/reperfusion, before coronary artery ligation (CAL) for 40 min at 36.5 î Hearts were treated with mitochondrial or sarcolemmal KATP channel blockers before LPC or LPostC. For post-conditioning, hearts received three 30 s cycles of ischaemia/reperfusion or levosimendan/vehicle. Hearts were pretreated with levosimendan immediately before CAL (without washout). Cardiac function, infarct size and reperfusion injury salvage kinase activity was assessed. Key results: LPC and LPostC halved the infarct size compared with controls (P<0.05). Treatment with KATP channel blockers before LPC or LPostC reversed this decrease. Pretreating hearts with levosimendan increased activity of extracellular signal-regulated kinase (ERK) 42/44 on reperfusion and had the most marked infarct-lowering effect (P<0.05). Conclusions and implications: (1) Hearts could be pharmacologically pre- and post-conditioned with levosimendan; (2) levosimendan pretreatment is the most effective way to reduce infarct size, possibly by increasing ERK 42/44 activity; (3) benefits of LPC and LPostC were abolished by both KATP channel blockers and (4) LPC may be useful before elective cardiac surgery, whereas LPostC may be used after acute coronary artery events.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.format.extent194750 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherJohn Wiley & Sonsen_US
dc.publisher.placeUnited Kingdomen_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom41en_US
dc.relation.ispartofpageto50en_US
dc.relation.ispartofissue1en_US
dc.relation.ispartofjournalBritish Journal of Pharmacologyen_US
dc.relation.ispartofvolume154en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchCardiology (incl. Cardiovascular Diseases)en_US
dc.subject.fieldofresearchcode110201en_US
dc.titleA role for the RISK pathway and KATP channels in pre- and post-conditioning induced by levosimendan in the isolated guinea pig hearten_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightCopyright 2008 The British Pharmacological Society. Published by Blackwell Publishing Ltd. This is the author-manuscript version of the paper. Reproduced in accordance with the copyright policy of the publisher. The definitive version is available at www.blackwell-synergy.comen_AU
gro.date.issued2008
gro.hasfulltextFull Text


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