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dc.contributor.authorStorm, Benjamin
dc.contributor.authorLudviksen, Judith K
dc.contributor.authorChristiansen, Dorte
dc.contributor.authorFure, Hilde
dc.contributor.authorPettersen, Kristin
dc.contributor.authorLandsem, Anne
dc.contributor.authorNilsen, Bent Aksel
dc.contributor.authorDybwik, Knut Gustav
dc.contributor.authorBraaten, Tonje
dc.contributor.authorNielsen, Erik Waage
dc.contributor.authorMollnes, Tom Eirik
dc.date.accessioned2022-08-04T09:12:38Z
dc.date.available2022-08-04T09:12:38Z
dc.date.issued2022-03-15
dc.description.abstractIntroduction: Air embolism may complicate invasive medical procedures. Bubbles trigger complement C3-mediated cytokine release, coagulation, and platelet activation in vitro in human whole blood. Since these findings have not been verified in vivo, we aimed to examine the effects of air embolism in pigs on thromboinflammation.<p> <p>Methods: Forty-five landrace pigs, average 17 kg (range 8.5-30), underwent intravenous air infusion for 300 or 360 minutes (n=29) or served as sham (n=14). Fourteen pigs were excluded due to e.g. infections or persistent foramen ovale. Blood was analyzed for white blood cells (WBC), complement activation (C3a and terminal C5b-9 complement complex [TCC]), cytokines, and hemostatic parameters including thrombin-antithrombin (TAT) using immunoassays and rotational thromboelastometry (ROTEM). Lung tissue was analyzed for complement and cytokines using qPCR and immunoassays. Results are presented as medians with interquartile range.<p> <p>Results: In 24 pigs receiving air infusion, WBC increased from 17×109/L (10-24) to 28 (16-42) (p<0.001). C3a increased from 21 ng/mL (15-46) to 67 (39-84) (p<0.001), whereas TCC increased only modestly (p=0.02). TAT increased from 35 µg/mL (28-42) to 51 (38-89) (p=0.002). ROTEM changed during first 120 minutes: Clotting time decreased from 613 seconds (531-677) to 538 (399-620) (p=0.006), clot formation time decreased from 161 seconds (122-195) to 124 (83-162) (p=0.02) and α-angle increased from 62 degrees (57-68) to 68 (62-74) (p=0.02). In lungs from pigs receiving air compared to sham animals, C3a was 34 ng/mL (14-50) versus 4.1 (2.4-5.7) (p<0.001), whereas TCC was 0.3 CAU/mL (0.2-0.3) versus 0.2 (0.1-0.2) (p=0.02). Lung cytokines in pigs receiving air compared to sham animals were: IL-1β 302 pg/mL (190-437) versus 107 (66-120), IL-6 644 pg/mL (358-1094) versus 25 (23-30), IL-8 203 pg/mL (81-377) versus 21 (20-35), and TNF 113 pg/mL (96-147) versus 16 (13-22) (all p<0.001). Cytokine mRNA in lung tissue from pigs receiving air compared to sham animals increased 12-fold for IL-1β, 121-fold for IL-6, and 17-fold for IL-8 (all p<0.001).<p> <p>Conclusion: Venous air embolism in pigs activated C3 without a corresponding C5 activation and triggered thromboinflammation, consistent with a C3-dependent mechanism. C3-inhibition might represent a therapeutic approach to attenuate this response.en_US
dc.identifier.citationStorm, Ludviksen, Christiansen, Fure, Pettersen, Landsem, Nilsen, Dybwik, Braaten, Nielsen, Mollnes. Venous Air Embolism Activates Complement C3 Without Corresponding C5 Activation and Trigger Thromboinflammation in Pigs. Frontiers in Immunology. 2022;13en_US
dc.identifier.cristinIDFRIDAID 2021483
dc.identifier.doi10.3389/fimmu.2022.839632
dc.identifier.issn1664-3224
dc.identifier.urihttps://hdl.handle.net/10037/25942
dc.language.isoengen_US
dc.publisherFrontiers Mediaen_US
dc.relation.ispartofStorm, B. (2022). Venous Air Embolism and Complement-driven Thromboinflammation. In vitro human whole blood studies and in vivo porcine studies on the effect of air emboli on the complement system, cytokine network, and the hemostasis. (Doctoral thesis). <a href=https://hdl.handle.net/10037/25922>https://hdl.handle.net/10037/25922</a>.
dc.relation.journalFrontiers in Immunology
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.titleVenous Air Embolism Activates Complement C3 Without Corresponding C5 Activation and Trigger Thromboinflammation in Pigsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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