{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T02:26:42Z","timestamp":1769912802749,"version":"3.49.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004362","name":"Swiss Heart Foundation","doi-asserted-by":"publisher","award":["FF20086"],"award-info":[{"award-number":["FF20086"]}],"id":[{"id":"10.13039\/501100004362","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>OBJECTIVES<\/jats:title>\n                  <jats:p>Donation after circulatory death provides excellent patient outcomes in heart transplantation; however, warm ischaemic graft damage remains a concern. We have reported that a brief period of hypothermic oxygenated perfusion prior to normothermic reperfusion improves graft recovery in a rat model. Here, we investigated the cardioprotective benefits and mechanisms of this approach compared to the current clinical standard in a large animal model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Circulatory death was induced in anaesthetized male Schweizer Edelschwein pigs (55\u2009kg). Hearts underwent 20\u2009min of warm, in-situ ischaemia, followed by a cold coronary flush and explantation. After 15\u2009min backtable preparation, hearts underwent either 15\u2009min cold static storage (control) or 30\u2009min hypothermic oxygenated perfusion. All hearts were perfused ex vivo under normothermic conditions; 3\u2009h in an unloaded mode, followed by 1\u2009h with left ventricular loading to assess cardiac recovery.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Compared to control conditions (n\u2009=\u20095), hypothermic oxygenated perfusion (n\u2009=\u20095) increased recovery of left ventricular function (cardiac output and maximum relaxation rate, P\u2009&amp;lt;\u20090.001 for both) and decreased cell death marker release (heart-type fatty acid binding protein, P\u2009=\u20090.009 and myoglobin, P\u2009&amp;lt;\u20090.001). In parallel, hypothermic oxygenated perfusion reduced the release of succinate and the oxidative stress marker 8-hydroxy-2'-deoxyguanosine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>A brief period of hypothermic oxygenated perfusion, applied as a reperfusion therapy between graft procurement and normothermic machine perfusion, provides cardioprotection in a porcine model of donation after circulatory death. Hypothermic oxygenated perfusion is a promising, easily applicable, cardioprotective reperfusion strategy; this study provides key evidence to support clinical translation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejcts\/ezaf061","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T19:22:47Z","timestamp":1741375367000},"source":"Crossref","is-referenced-by-count":1,"title":["Brief hypothermic oxygenated perfusion provides cardioprotection in a pig model of donation after circulatory death"],"prefix":"10.1093","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6368-7397","authenticated-orcid":false,"given":"Manuel","family":"Egle","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern,","place":["Switzerland"]},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Segiser","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexia","family":"Clavier","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern,","place":["Switzerland"]},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Beer","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern,","place":["Switzerland"]},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Helmer","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern,","place":["Switzerland"]},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahel","family":"Ottersberg","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern,","place":["Switzerland"]},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selianne","family":"Graf","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern,","place":["Switzerland"]},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4146-404X","authenticated-orcid":false,"given":"Maria","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Zulauf","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Lagger","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maris","family":"Bartkevics","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Kadner","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daja","family":"Krummenacher","sequence":"additional","affiliation":[{"name":"Magnetic Resonance Methodology Group, Institute of Diagnostic and Interventional Neuroradiology, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Vermathen","sequence":"additional","affiliation":[{"name":"Magnetic Resonance Methodology Group, Institute of Diagnostic and Interventional Neuroradiology, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3305-9343","authenticated-orcid":false,"given":"Matthias","family":"Siepe","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8489-917X","authenticated-orcid":false,"given":"Sarah","family":"Longnus","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Inselspital, Bern University Hospital and University of Bern , Bern,","place":["Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"2025031903572995000_ezaf061-B1","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"European Heart Journal"},{"key":"2025031903572995000_ezaf061-B2"},{"key":"2025031903572995000_ezaf061-B3","doi-asserted-by":"crossref","first-page":"S305","DOI":"10.1016\/j.ajt.2024.01.016","article-title":"OPTN\/SRTR 2022 Annual Data Report: heart","volume":"24","author":"Colvin","year":"2024","journal-title":"Am J Transplant"},{"key":"2025031903572995000_ezaf061-B4","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s12055-020-00998-x","article-title":"DCD donations and outcomes of heart transplantation: the Australian experience","volume":"36","author":"Dhital","year":"2020","journal-title":"Indian J Thorac Cardiovasc Surg"},{"key":"2025031903572995000_ezaf061-B5","first-page":"1114","article-title":"Early outcomes of heart transplantation using donation after circulatory death donors in the United States","volume":"11","author":"Kwon","year":"2022","journal-title":"Circ Heart Fail."},{"key":"2025031903572995000_ezaf061-B6","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.healun.2020.10.001","article-title":"A 5-year single-center early experience of heart transplantation from donation after circulatory-determined death donors","volume":"39","author":"Messer","year":"2020","journal-title":"J Heart Lung Transplant"},{"key":"2025031903572995000_ezaf061-B7","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1056\/NEJMoa2212438","article-title":"Transplantation outcomes with donor hearts after circulatory death","volume":"388","author":"Schroder","year":"2023","journal-title":"N Engl J Med"},{"key":"2025031903572995000_ezaf061-B8","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/nrcardio.2014.45","article-title":"Heart transplantation with donation after circulatory determination of death","volume":"11","author":"Longnus","year":"2014","journal-title":"Nat Rev Cardiol"},{"key":"2025031903572995000_ezaf061-B9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fcvm.2018.00008","article-title":"Transplantation of hearts donated after circulatory death","volume":"5","author":"White","year":"2018","journal-title":"Front Cardiovasc Med"},{"key":"2025031903572995000_ezaf061-B10","first-page":"1","article-title":"Heart transplantation with donation after circulatory death: what have we learned from preclinical studies?","volume":"12","author":"Niederberger","year":"2019","journal-title":"Circ: Heart Failure"},{"key":"2025031903572995000_ezaf061-B11","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.healun.2024.02.1456","article-title":"Post-transplant survival after normothermic regional perfusion versus direct procurement and perfusion in donation after circulatory determination of death in heart transplantation","volume":"43","author":"Ran","year":"2024","journal-title":"J Heart Lung Transplant"},{"key":"2025031903572995000_ezaf061-B12","first-page":"464","article-title":"Hypothermic oxygenated perfusion in liver transplantation: a meta-analysis of randomized controlled trials and matched studies","volume":"110","author":"Tang","year":"2024","journal-title":"Int J Surg"},{"key":"2025031903572995000_ezaf061-B13","doi-asserted-by":"crossref","first-page":"79","DOI":"10.57603\/EJT-011","article-title":"Hypothermic perfusion of the kidney: from research to clinical practice","volume":"1","author":"Radi","year":"2023","journal-title":"Eur J Transplant"},{"key":"2025031903572995000_ezaf061-B14","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.healun.2023.01.014","article-title":"Ex-situ oxygenated hypothermic machine perfusion in donation after circulatory death heart transplantation following either direct procurement or in-situ normothermic regional perfusion","volume":"42","author":"Moeslund","year":"2023","journal-title":"J Heart Lung Transplant"},{"key":"2025031903572995000_ezaf061-B15","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.healun.2024.07.018","article-title":"Successful clinical transplantation of hearts donated after circulatory death using direct procurement followed by hypothermic oxygenated perfusion: a report of the first 3 cases","volume":"43","author":"Brouckaert","year":"2024","journal-title":"J Heart Lung Transplant"},{"key":"2025031903572995000_ezaf061-B16","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1111\/ajt.16258","article-title":"Hypothermic, oxygenated perfusion (HOPE) provides cardioprotection via succinate oxidation prior to normothermic perfusion in a rat model of donation after circulatory death (DCD)","volume":"21","author":"Wyss","year":"2021","journal-title":"Am J Transplant"},{"key":"2025031903572995000_ezaf061-B17","doi-asserted-by":"crossref","first-page":"e033503","DOI":"10.1161\/JAHA.123.033503","article-title":"Hypothermic oxygenated perfusion improves vascular and contractile function by preserving endothelial nitric oxide production in cardiac grafts obtained with donation after circulatory death","volume":"13","author":"Egle","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"2025031903572995000_ezaf061-B18","doi-asserted-by":"crossref","first-page":"1325160","DOI":"10.3389\/fcvm.2024.1325160","article-title":"Open- vs. closed-chest pig models of donation after circulatory death","volume":"11","author":"Hubacher","year":"2024","journal-title":"Front Cardiovasc Med"},{"key":"2025031903572995000_ezaf061-B19","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.healun.2024.08.016","article-title":"Circulating factors, in both donor and ex vivo heart perfusion, correlate with heart recovery in a pig model of DCD","volume":"44","author":"Graf","year":"2025","journal-title":"J Heart Lung Transplant"},{"key":"2025031903572995000_ezaf061-B20","doi-asserted-by":"crossref","first-page":"417","DOI":"10.2307\/2531823","article-title":"An improved sequentially rejective Bonferroni test procedure","volume":"43","author":"Holland","year":"1987","journal-title":"Biometrics"},{"key":"2025031903572995000_ezaf061-B21","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s40472-014-0046-1","article-title":"Hypothermic oxygenated liver perfusion: basic mechanisms and clinical application","volume":"2","author":"Schlegel","year":"2015","journal-title":"Curr Transplant Rep"},{"key":"2025031903572995000_ezaf061-B22","doi-asserted-by":"crossref","first-page":"5403","DOI":"10.3390\/ijms24065403","article-title":"Hypothermic oxygenated machine perfusion promotes mitophagy flux against hypoxia-ischemic injury in Rat DCD liver","volume":"24","author":"Luo","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2025031903572995000_ezaf061-B23","doi-asserted-by":"crossref","first-page":"e026135","DOI":"10.1161\/JAHA.122.026135","article-title":"Inhibiting succinate release worsens cardiac reperfusion injury by enhancing mitochondrial reactive oxygen species generation","volume":"11","author":"Milliken","year":"2022","journal-title":"J Am Heart Assoc"},{"key":"2025031903572995000_ezaf061-B24","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.immuni.2013.11.010","article-title":"The interleukin-1 family: back to the future","volume":"39","author":"Garlanda","year":"2013","journal-title":"Immunity"},{"key":"2025031903572995000_ezaf061-B25","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2119\/molmed.2014.00034","article-title":"Interleukin-18 as a therapeutic target in acute myocardial infarction and heart failure","volume":"20","author":"O\u2019Brien","year":"2014","journal-title":"Mol Med"},{"key":"2025031903572995000_ezaf061-B26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0091-6749(99)70518-X","article-title":"IL-18: a TH1 -inducing, proinflammatory cytokine and new member of the IL-1 family","volume":"103","author":"Dinarello","year":"1999","journal-title":"J Allergy Clin Immunol"},{"key":"2025031903572995000_ezaf061-B27","doi-asserted-by":"crossref","first-page":"20221","DOI":"10.1074\/jbc.M313980200","article-title":"Activation of intrinsic and extrinsic proapoptotic signaling pathways in interleukin-18-mediated human cardiac endothelial cell death","volume":"279","author":"Chandrasekar","year":"2004","journal-title":"J Biol Chem"},{"key":"2025031903572995000_ezaf061-B28","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1128\/iai.57.2.590-595.1989","article-title":"Endotoxin-induced serum factor that stimulates gamma interferon production","volume":"57","author":"Nakamura","year":"1989","journal-title":"Infect Immun"},{"key":"2025031903572995000_ezaf061-B29","doi-asserted-by":"crossref","first-page":"1126391","DOI":"10.3389\/fcvm.2023.1126391","article-title":"Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation","volume":"10","author":"Xu","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"2025031903572995000_ezaf061-B30","doi-asserted-by":"crossref","first-page":"e14044","DOI":"10.1111\/ctr.14044","article-title":"Targeting the NLRP3 inflammasome to reduce warm ischemic injury in donation after circulatory death heart","volume":"34","author":"Quader","year":"2020","journal-title":"Clin Transplant"},{"key":"2025031903572995000_ezaf061-B31","doi-asserted-by":"crossref","first-page":"5249","DOI":"10.1128\/IAI.69.9.5249-5263.2001","article-title":"Cellular mechanisms that cause suppressed gamma interferon secretion in endotoxin-tolerant mice","volume":"69","author":"Varma","year":"2001","journal-title":"Infect Immun"},{"key":"2025031903572995000_ezaf061-B32","doi-asserted-by":"crossref","first-page":"107475","DOI":"10.1016\/j.intimp.2021.107475","article-title":"The role of interleukin-10 family members in cardiovascular diseases","volume":"94","author":"Xu","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"2025031903572995000_ezaf061-B33","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1161\/CIRCRESAHA.108.188243","article-title":"IL-10 inhibits inflammation and attenuates left ventricular remodeling after myocardial infarction via activation of STAT3 and suppression of HuR","volume":"104","author":"Krishnamurthy","year":"2009","journal-title":"Circ Res"},{"key":"2025031903572995000_ezaf061-B34","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1161\/01.CIR.101.9.1019","article-title":"Crucial role of endogenous interleukin-10 production in myocardial ischemia\/reperfusion injury","volume":"101","author":"Yang","year":"2000","journal-title":"Circulation"},{"key":"2025031903572995000_ezaf061-B35","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1172\/JCI62874","article-title":"Myocardial ischemia-reperfusion injury: a neglected therapeutic target","volume":"123","author":"Hausenloy","year":"2013","journal-title":"J Clin Invest"}],"container-title":["European Journal of Cardio-Thoracic Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejcts\/advance-article-pdf\/doi\/10.1093\/ejcts\/ezaf061\/62340429\/ezaf061.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejcts\/article-pdf\/67\/3\/ezaf061\/62340429\/ezaf061.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejcts\/article-pdf\/67\/3\/ezaf061\/62340429\/ezaf061.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T03:57:50Z","timestamp":1742356670000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejcts\/article\/doi\/10.1093\/ejcts\/ezaf061\/8063619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,4]]}},"URL":"https:\/\/doi.org\/10.1093\/ejcts\/ezaf061","relation":{},"ISSN":["1873-734X"],"issn-type":[{"value":"1873-734X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2025,3]]},"article-number":"ezaf061"}}