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dc.contributor.authorPischke, Søren Erik
dc.contributor.authorGustavsen, Alice
dc.contributor.authorOrrem, Hilde Lang
dc.contributor.authorEgge, Kjetil Hagene
dc.contributor.authorCourivaud, Frederic 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.accessioned2018-05-22T10:32:08Z
dc.date.available2018-05-22T10:32:08Z
dc.date.issued2017-03-03
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.en_US
dc.descriptionSource at: <a href=http://doi.org/10.1007/s00395-017-0610-9> http://doi.org/10.1007/s00395-017-0610-9</a>. Licensed <a href=http://creativecommons.org/licenses/by-nc-nd/4.0/> CC BY-NC-ND 4.0. </a>en_US
dc.identifier.citationPischke, S. E., Gustavsen, A., Orrem, H., Egge, K. H., Courivaud, F. A. A., Fontenelle, H., ... Mollnes, T. E. (2017). Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function. Basic Research in Cardiology, 112:20(3), 1-14. http://doi.org/10.1007/s00395-017-0610-9en_US
dc.identifier.cristinIDFRIDAID 1472576
dc.identifier.doi10.1007/s00395-017-0610-9
dc.identifier.issn0300-8428
dc.identifier.issn1435-1803
dc.identifier.urihttps://hdl.handle.net/10037/12746
dc.language.isoengen_US
dc.publisherSpringeren_US
dc.relation.journalBasic Research in Cardiology
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/SFF/223255/Norway/Centre of Molecular Inflammation Research/CEMIR/en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Kardiologi: 771en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Cardiology: 771en_US
dc.titleComplement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac functionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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