{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:29:06Z","timestamp":1779366546459,"version":"3.53.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,5,16]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are debilitating diseases with a high mortality. Despite emerging treatments, pulmonary vascular resistance frequently remains elevated. However, the ketone body 3\u2010hydroxybutyrate (3\u2010OHB) may reduce pulmonary vascular resistance in these patients. Hence, the aim was to assess the hemodynamic effects of 3\u2010OHB in patients with PAH or CTEPH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We enrolled patients with PAH (n=10) or CTEPH (n=10) and residual pulmonary hypertension. They received 3\u2010OHB infusion and placebo (saline) for 2\u2009hours in a randomized crossover study. Invasive hemodynamic and echocardiography measurements were performed. Furthermore, we investigated the effects of 3\u2010OHB on the right ventricle of isolated hearts and isolated pulmonary arteries from Sprague\u2013Dawley rats. Ketone body infusion increased circulating 3\u2010OHB levels from 0.5\u00b10.5 to 3.4\u00b10.7\u2009mmol\/L (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Cardiac output improved by 1.2\u00b10.1 L\/min (27\u00b13%,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), and right ventricular annular systolic velocity increased by 1.4\u00b10.4\u2009cm\/s (13\u00b14%,\n              <jats:italic>P<\/jats:italic>\n              =0.002). Pulmonary vascular resistance decreased by 1.3\u00b10.3 Wood units (18%\u00b14%,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) with no significant difference in response between patients with PAH and CTEPH. In the rat studies, 3\u2010OHB administration was associated with decreased pulmonary arterial tension compared with saline administration (maximal relative tension difference: 12\u00b12%,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and had no effect on right ventricular systolic pressures (\n              <jats:italic>P<\/jats:italic>\n              =0.63), whereas pressures rose at a slower pace (dP\/dtmax,\n              <jats:italic>P<\/jats:italic>\n              =0.02).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">In patients with PAH or CTEPH, ketone body infusion improves cardiac output and decreases pulmonary vascular resistance. Experimental rat studies support that ketone bodies relax pulmonary arteries. Long\u2010term studies are warranted to assess the clinical role of hyperketonemia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT04615754.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.028232","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T10:13:52Z","timestamp":1684145632000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Hemodynamic Effects of Ketone Bodies in Patients With Pulmonary Hypertension"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9228-3869","authenticated-orcid":false,"given":"Roni","family":"Nielsen","sequence":"first","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian Hylleberg","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigopan","family":"Gopalasingam","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristoffer","family":"Berg\u2010Hansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-5878","authenticated-orcid":false,"given":"Jacob","family":"Seefeldt","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-8109","authenticated-orcid":false,"given":"Casper","family":"Homilius","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5078-9279","authenticated-orcid":false,"given":"Ebbe","family":"Boedtkjer","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads J\u00f8nsson","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9753-4142","authenticated-orcid":false,"given":"Henrik","family":"Wiggers","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5627-7322","authenticated-orcid":false,"given":"Niels","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Medical\/Steno Aarhus Research Laboratory Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Erik","family":"B\u00f8tker","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-2387","authenticated-orcid":false,"given":"S\u00f8ren","family":"Mellemkj\u00e6r","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus 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