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dc.contributor.authorPischke, Søren
dc.contributor.authorHestenes, Siv Merete
dc.contributor.authorJohansen, Harald Thidemann
dc.contributor.authorFure, Hilde
dc.contributor.authorBugge, Jan F
dc.contributor.authorEspinoza, Andreas Westenvik
dc.contributor.authorSkulstad, Helge
dc.contributor.authorEdvardsen, Thor
dc.contributor.authorFosse, Erik
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorHalvorsen, Per Steinar
dc.contributor.authorNielsen, Erik Waage
dc.date.accessioned2019-09-11T10:57:38Z
dc.date.available2019-09-11T10:57:38Z
dc.date.issued2019-06-27
dc.description.abstract<i>Introduction</i> - Right ventricular (RV) myocardial dysfunction is a common feature in septic shock. It can worsen outcome, but the etiology is poorly understood. Pulmonary artery hypertension (PAH) plays a part in the pathogenesis of the right heart dysfunction in sepsis but its importance is unknown. In pigs, PAH in sepsis is substantial and the translational value of porcine sepsis models therefore questioned. We hypothesized that porcine sepsis causes a myocardial inflammatory response which leads to myocardial dysfunction independent of PAH.<p> <p><i>Materials and methods</i> - Sepsis was induced by <i>Escherichia coli-infusion</i> in 10 pigs resulting in PAH and increased right ventricular pressure (RVP). The same degree of RVP was achieved by external pulmonary artery banding (PAB) in a consecutive series of 6 animals.<p> <p><i>Results</i> - Sepsis, but not PAB, led to increase in endothelial damage marker PAI-1 and cytokines TNF and IL-6 (all p<0.05) in plasma. In myocardium, TNF and IL-6 were significantly elevated in sepsis, TNF in both ventricles and IL-6 mostly in RV, while IL-1β, IL-18 and C5a were significantly higher in RV compared to LV after PAB (all p<0.05). Myocardial mRNA levels of IL-1β, IL-6, IL-18, IP-10, E-selectin and PAI-1 were significantly elevated in RV and LV during sepsis compared to PAB, while Caspase-1 was decreased in septic compared to PAB animals (all p<0.05). Cathepsin L activity was increased in RV by PAB, while sepsis inhibited this response. <i>Escherichia coli</i>-induced sepsis caused myocardial inflammation independent of PAH.<p> <p><i>Conclusion</i> - Prominent PAH should therefore not exclude porcine sepsis models to further our understanding of human sepsis.en_US
dc.description.sponsorshipNorwegian Research Council Norwegian Council for Cardiovascular Diseases The Odd Fellow Foundation The Simon Fougner Hartmann Family Fund European Community's Seventh Framework Programmeen_US
dc.descriptionSource at <a href=https://doi.org/10.1371/journal.pone.0218624>https://doi.org/10.1371/journal.pone.0218624. </a>en_US
dc.identifier.citationPischke, S.E., Hestenes, S., Johansen, H.T., Fure, H., Bugge, J.F., Espinoza, A. ... Nielsen, E.W. (2019). Sepsis causes right ventricular myocardial inflammation independent of pulmonary hypertension in a porcine sepsis model. PLOS ONE, 14</i>(6): e0218624. https://doi.org/10.1371/journal.pone.0218624en_US
dc.identifier.issn1932-6203
dc.identifier.otherFRIDAID 1722520
dc.identifier.other10.1371/journal.pone.0218624
dc.identifier.urihttps://hdl.handle.net/10037/16160
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.journalPLOS ONE
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleSepsis causes right ventricular myocardial inflammation independent of pulmonary hypertension in a porcine sepsis modelen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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