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dc.contributor.authorGiblett, Joel Pen
dc.contributor.authorAxell, Richard Gen
dc.contributor.authorWhite, Paul Aen
dc.contributor.authorClarke, Sophie Jen
dc.contributor.authorMcCormick, Liamen
dc.contributor.authorRead, Philip Aen
dc.contributor.authorReinhold, Johannesen
dc.contributor.authorBrown, Adamen
dc.contributor.authorO’Sullivan, Michaelen
dc.contributor.authorWest, Nick EJen
dc.contributor.authorDutka, David Pen
dc.contributor.authorHoole, Stephen Pen
dc.date.accessioned2016-09-29T15:08:30Z
dc.date.available2016-09-29T15:08:30Z
dc.date.issued2016-07-19en
dc.identifier.citationCardiovascular Diabetology. 2016 Jul 19;15(1):99
dc.identifier.issn1475-2840
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/260577
dc.description.abstractAbstract Background Glucagon-like peptide-1 (7–36) amide (GLP-1) protects against stunning and cumulative left ventricular dysfunction in humans. The mechanism remains uncertain but GLP-1 may act by opening mitochondrial K-ATP channels in a similar fashion to ischemic conditioning. We investigated whether blockade of K-ATP channels with glibenclamide abrogated the protective effect of GLP-1 in humans. Methods Thirty-two non-diabetic patients awaiting stenting of the left anterior descending artery (LAD) were allocated into 4 groups (control, glibenclamide, GLP-1, and GLP-1 + glibenclamide). Glibenclamide was given orally prior to the procedure. A left ventricular conductance catheter recorded pressure–volume loops during a 1-min low-pressure balloon occlusion (BO1) of the LAD. GLP-1 or saline was then infused for 30-min followed by a further 1-min balloon occlusion (BO2). In a non-invasive study, 10 non-diabetic patients were randomized to receive two dobutamine stress echocardiograms (DSE) during GLP-1 infusion with or without oral glibenclamide pretreatment. Results GLP-1 prevented stunning even with glibenclamide pretreatment; the Δ % dP/dtmax 30-min post-BO1 normalized to baseline after GLP-1: 0.3 ± 6.8 % (p = 0.02) and GLP-1 + glibenclamide: −0.8 ± 9.0 % (p = 0.04) compared to control: −11.5 ± 10.0 %. GLP-1 also reduced cumulative stunning after BO2: −12.8 ± 10.5 % (p = 0.02) as did GLP-1 + glibenclamide: −14.9 ± 9.2 % (p = 0.02) compared to control: −25.7 ± 9.6 %. Glibenclamide alone was no different to control. Glibenclamide pretreatment did not affect global or regional systolic function after GLP-1 at peak DSE stress (EF 74.6 ± 6.4 vs. 74.0 ± 8.0, p = 0.76) or recovery (EF 61.9 ± 5.7 vs. 61.4 ± 5.6, p = 0.74). Conclusions Glibenclamide pretreatment does not abrogate the protective effect of GLP-1 in human models of non-lethal myocardial ischemia. Trial registration Clinicaltrials.gov Unique Identifier: NCT02128022
dc.titleGlucagon-like peptide-1 derived cardioprotection does not utilize a KATP-channel dependent pathway: mechanistic insights from human supply and demand ischemia studiesen
dc.typeArticle
dc.date.updated2016-09-29T15:08:30Z
dc.language.rfc3066en
dc.rights.holderThe Author(s)
prism.publicationDate2016en
dc.identifier.doi10.17863/CAM.4811
dcterms.dateAccepted2016-06-30en
rioxxterms.versionofrecord10.1186/s12933-016-0416-3en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-07-19en
dc.identifier.eissn1475-2840
rioxxterms.typeJournal Article/Reviewen


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