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Hertz og Hustru Inger Hertz Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006088","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012526","name":"Sundhedsvidenskabelige Fakultet, Aarhus Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012526","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007605","name":"Aarhus Universitet","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007605","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Basic Res Cardiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Cardiogenic shock (CS) is characterized by reduced cardiac output (CO), reduced end-organ perfusion, and high mortality. Medical therapies have failed to improve survival. The ketone body 3-hydroxybutyrate (3-OHB) enhances cardiac function in heart failure and CS. We aimed to elucidate the cardiovascular and cardiometabolic effects of 3-OHB treatment during CS. In a randomized, assessor-blinded crossover design, we studied 16 female pigs (60\u00a0kg, 5\u00a0months of age). CS was induced by left main coronary artery microsphere injections. Predefined criteria for CS were a 30% reduction in CO or mixed venous saturation (SvO<jats:sub>2<\/jats:sub>). Intravenous 3-OHB infusion and a matching control solution were administered for 120\u00a0min in random order. Hemodynamic measurements were obtained by pulmonary artery catheterization and a left ventricular (LV) pressure\u2013volume catheter. Myocardial mitochondrial function was assessed using high resolution respirometry. During CS, infusion with 3-OHB increased CO by 0.9\u00a0L\/min (95%CI 0.4\u20131.3\u00a0L\/min) compared with control infusion. SvO<jats:sub>2<\/jats:sub> (<jats:italic>P<\/jats:italic>\u2009=\u20090.026) and heart rate (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) increased. Stroke volume (<jats:italic>P<\/jats:italic>\u2009=\u20090.6) was not altered. LV\u00a0contractile function as determined by LV\u00a0end-systolic elastance improved during 3-OHB infusion compared with control infusion (<jats:italic>P<\/jats:italic>\u2009=\u20090.004). Systemic and pulmonary vascular resistance decreased, and diuresis increased. LV mitochondrial function was higher after 3-OHB infusion compared with control. We conclude that 3-OHB infusion enhances cardiac function by increasing contractility and reducing vascular resistance, while also preserving myocardial mitochondrial respiratory function in a large animal model of ischemic CS. These novel findings support the therapeutic potential of exogenous ketone supplementation in CS management.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s00395-025-01103-2","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T09:52:32Z","timestamp":1744451552000},"page":"579-596","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The ketone body 3-hydroxybutyrate increases cardiac output and cardiac contractility in a porcine model of cardiogenic shock: a randomized, blinded, crossover trial"],"prefix":"10.1007","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1009-3768","authenticated-orcid":false,"given":"Oskar Kj\u00e6rgaard","family":"H\u00f8rsdal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4459-4291","authenticated-orcid":false,"given":"Alexander M\u00f8ller","family":"Larsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3014-083X","authenticated-orcid":false,"given":"Kasper Lykke","family":"Wethelund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7287-9793","authenticated-orcid":false,"given":"Frederik Flyvholm","family":"Dalsgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-5878","authenticated-orcid":false,"given":"Jacob Marthinsen","family":"Seefeldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3847-8758","authenticated-orcid":false,"given":"Ole Kristian Lerche","family":"Helgestad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0827-5263","authenticated-orcid":false,"given":"Niels","family":"Moeslund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-5845","authenticated-orcid":false,"given":"Jacob Eifer","family":"M\u00f8ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4702-5195","authenticated-orcid":false,"given":"Hanne Berg","family":"Ravn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9228-3869","authenticated-orcid":false,"given":"Roni Rangh\u00f8j","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9753-4142","authenticated-orcid":false,"given":"Henrik","family":"Wiggers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5110-0656","authenticated-orcid":false,"given":"Kristoffer","family":"Berg-Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6363-7406","authenticated-orcid":false,"given":"Nigopan","family":"Gopalasingam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,12]]},"reference":[{"key":"1103_CR1","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/S0735-1097(87)80223-1","volume":"9","author":"JL Anderson","year":"1987","unstructured":"Anderson JL, Baim DS, Fein SA, Goldstein RA, LeJemtel TH, Likoff MJ (1987) Efficacy and safety of sustained (48 hour) intravenous infusions of milrinone in patients with severe congestive heart failure: a multicenter study. 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