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We aimed to characterize the effects of M0 and M1 macrophage\u2010derived EV administration on post\u2010ischaemic functional recovery and glucose metabolism using an isolated rat heart model of DCD. Isolated rat hearts were subjected to 20\u2009min aerobic perfusion, followed by 27\u2009min global, warm ischaemia or continued aerobic perfusion and 60\u2009min reperfusion with or without intravascular administration of EV. Four experimental groups were compared: (1) no ischaemia, no EV; (2) ischaemia, no EV; (3) ischaemia with M0\u2010macrophage\u2010dervied EV; (4) ischaemia with M1\u2010macrophage\u2010derived EV. Post\u2010ischaemic ventricular and metabolic recovery were evaluated. During reperfusion, ventricular function was decreased in untreated ischaemic and M1\u2010EV hearts, but not in M0\u2010EV hearts, compared to non\u2010ischaemic hearts (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In parallel with the reduced functional recovery in M1\u2010EV versus M0\u2010EV ischaemic hearts, rates of glycolysis from exogenous glucose and oxidative metabolism tended to be lower, while rates of glycogenolysis and lactate release tended to be higher. EV from M0\u2010 and M1\u2010macrophages differentially affect post\u2010ischaemic cardiac recovery, potentially by altering glucose metabolism in a rat model of DCD. Targeted EV therapy may be a useful approach for modulating cardiac energy metabolism and optimizing graft quality in the setting of DCD.<\/jats:p>","DOI":"10.1111\/jcmm.18281","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T14:48:53Z","timestamp":1713883733000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Macrophage\u2010derived extracellular vesicles alter cardiac recovery and metabolism in a rat heart model of donation after circulatory death"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8708-4996","authenticated-orcid":false,"given":"Selianne","family":"Graf","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery Inselspital Bern University Hospital, University of Bern  Bern Switzerland"},{"name":"Department for BioMedical Research University of Bern  Bern Switzerland"},{"name":"Graduate School of Cellular and Biomedical Sciences University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1309-534X","authenticated-orcid":false,"given":"Vanessa","family":"Biemmi","sequence":"additional","affiliation":[{"name":"Laboratory for Cardiovascular Theranostics Cardiocentro Ticino Institute\u2010EOC  Lugano 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, University of Bern  Bern Switzerland"},{"name":"Department for BioMedical Research University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Segiser","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Inselspital Bern University Hospital, University of Bern  Bern Switzerland"},{"name":"Department for BioMedical Research University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Inselspital Bern University Hospital, University of Bern  Bern Switzerland"},{"name":"Department for BioMedical Research University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"M\u00e9ndez\u2010Carmona","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Inselspital Bern University Hospital, University of Bern  Bern Switzerland"},{"name":"Department for BioMedical Research University of Bern  Bern 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