{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:45:44Z","timestamp":1791312344319,"version":"4.3.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T00:00:00Z","timestamp":1647302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007137","name":"Helse Nord RHF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007137","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Air embolism may complicate invasive medical procedures. Bubbles trigger complement C3-mediated cytokine release, coagulation, and platelet activation<jats:italic>in vitro<\/jats:italic>in human whole blood. Since these findings have not been verified<jats:italic>in vivo<\/jats:italic>, we aimed to examine the effects of air embolism in pigs on thromboinflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 24 pigs receiving air infusion, WBC increased from 17\u00d710<jats:sup>9<\/jats:sup>\/L (10-24) to 28 (16-42) (p&amp;lt;0.001). C3a increased from 21 ng\/mL (15-46) to 67 (39-84) (p&amp;lt;0.001), whereas TCC increased only modestly (p=0.02). TAT increased from 35 \u00b5g\/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 \u03b1-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&amp;lt;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-1\u03b2 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&amp;lt;0.001). Cytokine mRNA in lung tissue from pigs receiving air compared to sham animals increased 12-fold for IL-1\u03b2, 121-fold for IL-6, and 17-fold for IL-8 (all p&amp;lt;0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.839632","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T07:47:21Z","timestamp":1647330441000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Venous Air Embolism Activates Complement C3 Without Corresponding C5 Activation and Trigger Thromboinflammation in Pigs"],"prefix":"10.3389","volume":"13","author":[{"given":"Benjamin S.","family":"Storm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith 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