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dc.contributor.authorPischke, Søren Erik
dc.contributor.authorGustavsen, Alice
dc.contributor.authorOrrem, HL
dc.contributor.authorEgge, Kjetil Hagene
dc.contributor.authorCourivaud, Fredric A A
dc.contributor.authorFontenelle, Hugues
dc.contributor.authorDespont, Alain
dc.contributor.authorBongoni, Anjan K.
dc.contributor.authorRieben, Robert
dc.contributor.authorTønnessen, Tor Inge
dc.contributor.authorNunn, Miles A.
dc.contributor.authorScott, Helge
dc.contributor.authorSkulstad, Helge
dc.contributor.authorBarratt-Due, Andreas
dc.contributor.authorMollnes, Tom Eirik
dc.date.accessioned2017-11-09T08:14:50Z
dc.date.available2017-11-09T08:14:50Z
dc.date.created2017-05-29T15:58:03Z
dc.date.issued2017
dc.identifier.citationBasic Research in Cardiology. 2017, 112:20 (3), 1-14.nb_NO
dc.identifier.issn0300-8428
dc.identifier.urihttp://hdl.handle.net/11250/2465089
dc.description.abstractInhibition of complement factor 5 (C5) reduced myocardial infarction in animal studies, while no benefit was found in clinical studies. Due to lack of cross-reactivity of clinically used C5 antibodies, different inhibitors were used in animal and clinical studies. Coversin (Ornithodoros moubata complement inhibitor, OmCI) blocks C5 cleavage and binds leukotriene B4 in humans and pigs. We hypothesized that inhibition of C5 before reperfusion will decrease infarct size and improve ventricular function in a porcine model of myocardial infarction. In pigs (Sus scrofa), the left anterior descending coronary artery was occluded (40 min) and reperfused (240 min). Coversin or placebo was infused 20 min after occlusion and throughout reperfusion in 16 blindly randomized pigs. Coversin significantly reduced myocardial infarction in the area at risk by 39% (p = 0.03, triphenyl tetrazolium chloride staining) and by 19% (p = 0.02) using magnetic resonance imaging. The methods correlated significantly (R = 0.92, p < 0.01). Tissue Doppler echocardiography showed increased systolic displacement (31%, p < 0.01) and increased systolic velocity (29%, p = 0.01) in coversin treated pigs. Interleukin-1β in myocardial microdialysis fluid was significantly reduced (31%, p < 0.05) and tissue E-selectin expression was significantly reduced (p = 0.01) in the non-infarcted area at risk by coversin treatment. Coversin ablated plasma C5 activation throughout the reperfusion period and decreased myocardial C5b-9 deposition, while neither plasma nor myocardial LTB4 were significantly reduced. Coversin substantially reduced the size of infarction, improved ventricular function, and attenuated interleukin-1β and E-selectin in this porcine model by inhibiting C5. We conclude that inhibition of C5 in myocardial infarction should be reconsidered.nb_NO
dc.language.isoengnb_NO
dc.publisherSpringer Verlagnb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleComplement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac functionnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.pagenumber1-14nb_NO
dc.source.volume112:20nb_NO
dc.source.journalBasic Research in Cardiologynb_NO
dc.source.issue3nb_NO
dc.identifier.doi10.1007/s00395-017-0610-9
dc.identifier.cristin1472576
dc.description.localcode© The Author(s) 2017. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)nb_NO
cristin.unitcode194,65,15,0
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal