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dc.contributor.authordu Toit, Eugene Francoisen_US
dc.contributor.authorRossouw, Ellenen_US
dc.contributor.authorSalie, Ruduwaanen_US
dc.contributor.authorOpie, Lionel Henryen_US
dc.contributor.authorLochner, Amandaen_US
dc.date.accessioned2017-05-03T15:31:40Z
dc.date.available2017-05-03T15:31:40Z
dc.date.issued2005en_US
dc.date.modified2009-09-14T07:15:40Z
dc.identifier.issn00071188en_US
dc.identifier.doi10.1007/s10557-005-6894-2en_AU
dc.identifier.urihttp://hdl.handle.net/10072/25666
dc.description.abstractWe have previously shown that NO-donor induced elevation in myocardial cGMP levels is associated with improved reperfusion function of the isolated rat heart. The phosphodiesterase 5 (PDE 5) inhibitor, sildenafil could potentially increase myocardial cGMP levels and thus protect the heart against ischaemic/reperfusion injury. Methods: To test our hypothesis we treated the isolated working rat heart with vehicle, OR sildenafil (10, 20, 50, 100, 200 nM), OR sildenafil (50 nM) plus a sarcolemmal (HMR 1098) or a mitochondrial (5-Hydroxydecanoate (5-HD)) KATP channel blocker. Hearts were then subjected to 20 min global, or 35 min regional ischaemia at 37C before reperfusion function (aortic output, coronary flow and aortic pressure) and infarct size were documented. Pre-ischaemic, ischaemic and reperfusion myocardial cAMP and cGMP concentrations were determined. Results: Low concentrations of sildenafil (10, 20 and 50 nM) improved reperfusion aortic output (AO) recovery (61.4ᠴ.5%, 64.8 ᠵ.2% and 62.3 ᠵ.0% vs. 45.4 ᠳ.8% for controls (p < 0.05)) and infarct size, while high concentrations (200 nM) worsened AO recovery (24.9 ᠴ.9.0%, p < 0.05). Myocardial cGMP levels of ischaemic tissue were elevated (34.7 ᠲ.4 vs. 27.3 ᠲ.2 pmol/g ww) and cAMP levels were suppressed (0.59 ᠰ.03 vs. 0.87 ᠰ.06 nmol/g ww) in the sildenafil (50 nM) treated hearts. Co-perfusion with sildenafil plus HMR 1098 decreased AO recovery (21.7 ᠷ.6% vs. 62.3 ᠵ.0% for sildenafil alone, p < 0.05) and increased infarct size (29.7 ᠲ.04% vs. 8.6 ᠲ.39% for sildenafil alone, p < 0.05).Similarly, sildenafil plus 5-HD decreased reperfusion AO recovery (44.4 ᠶ.0% vs. 62.3 ᠵ.0% for sildenafil alone, p < 0.05) and increased infarct size (33.8 ᠱ.62% vs. 8.6 ᠲ.39% for sildenafil alone, p < 0.05). Conclusions: (1) Pretreatment with low concentrations of sildenafil (20-50 nM) improves, while higher concentrations (200 nM) worsen reperfusion function in this model. (2) Low concentrations of sildenafil (20-50 nM) decrease infarct size while the higher concentrations had no effect. (3) These protective properties of low concentrations of sildenafil may be related to its cGMP elevating and cAMP suppressing effects in the ischaemic heart. (4) Possible end-effectors for sildenafil in the ischaemic heart include the mitochondrial and sarcolemmal KATP channel.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherNature Publishing Groupen_US
dc.publisher.placeLondon Englanden_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom23en_US
dc.relation.ispartofpageto31en_US
dc.relation.ispartofjournalCardiovascular Drugs and Therapyen_US
dc.relation.ispartofvolume19en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchCardiology (incl. Cardiovascular Diseases)en_US
dc.subject.fieldofresearchcode110201en_US
dc.titleEffect of sildenafil on reperfusion function, infarct size, and cyclic nucleotide levels in the isolated rat heart modelen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.date.issued2005
gro.hasfulltextNo Full Text


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