{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:38:15Z","timestamp":1790127495412,"version":"4.0.1"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2024,4,23]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Cardiolipin is a mitochondrial-specific phospholipid that maintains integrity of the electron transport chain (ETC) and plays a central role in myocardial ischemia\/reperfusion injury. Tafazzin is an enzyme that is required for cardiolipin maturation. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use to provide hemodynamic support for acute myocardial infarction has grown exponentially, is associated with poor outcomes, and is under active clinical investigation, yet the mechanistic effect of VA-ECMO on myocardial damage in acute myocardial infarction remains poorly understood. We hypothesized that VA-ECMO acutely depletes myocardial cardiolipin and exacerbates myocardial injury in acute myocardial infarction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>We examined cardiolipin and tafazzin levels in human subjects with heart failure and healthy swine exposed to VA-ECMO and used a swine model of closed-chest myocardial ischemia\/reperfusion injury to evaluate the effect of VA-ECMO on cardiolipin expression, myocardial injury, and mitochondrial function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Cardiolipin and tafazzin levels are significantly reduced in the left ventricles of individuals requiring VA-ECMO compared with individuals without VA-ECMO before heart transplantation. Six hours of exposure to VA-ECMO also decreased left ventricular levels of cardiolipin and tafazzin in healthy swine compared with sham controls. To explore whether cardiolipin depletion by VA-ECMO increases infarct size, we performed left anterior descending artery occlusion for a total of 120 minutes followed by 180 minutes of reperfusion in adult swine in the presence and absence of MTP-131, an amphipathic molecule that interacts with cardiolipin to stabilize the inner mitochondrial membrane. Compared with reperfusion alone, VA-ECMO activation beginning after 90 minutes of left anterior descending artery occlusion increased infarct size (36\u00b18% versus 48\u00b17%;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001). VA-ECMO also decreased cardiolipin and tafazzin levels, disrupted mitochondrial integrity, reduced electron transport chain function, and promoted oxidative stress. Compared with reperfusion alone or VA-ECMO before reperfusion, delivery of MTP-131 before VA-ECMO activation reduced infarct size (22\u00b18%;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.03 versus reperfusion alone and\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001 versus VA-ECMO alone). MTP-131 restored cardiolipin and tafazzin levels, stabilized mitochondrial function, and reduced oxidative stress in the left ventricle.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>We identified a novel mechanism by which VA-ECMO promotes myocardial injury and further identify cardiolipin as an important target of therapy to reduce infarct size and to preserve mitochondrial function in the setting of VA-ECMO for acute myocardial infarction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.123.065298","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T10:00:39Z","timestamp":1705572039000},"page":"1341-1353","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Novel Role for Cardiolipin as a Target of Therapy to Mitigate Myocardial Injury Caused by Venoarterial Extracorporeal Membrane Oxygenation"],"prefix":"10.1161","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7713-606X","authenticated-orcid":true,"given":"Lija","family":"Swain","sequence":"first","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0393-0978","authenticated-orcid":true,"given":"Shreyas","family":"Bhave","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Qiao","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6242-5926","authenticated-orcid":true,"given":"Lara","family":"Reyelt","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay D.","family":"Everett","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Awata","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8288-7992","authenticated-orcid":true,"given":"Rahul","family":"Raghav","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah N.","family":"Powers","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genya","family":"Sunagawa","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9200-2385","authenticated-orcid":true,"given":"Peter S.","family":"Natov","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Mahmoudi","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Warner","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Couper","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3580-5664","authenticated-orcid":true,"given":"Masashi","family":"Kawabori","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tejasvi","family":"Aryaputra","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon S.","family":"Huggins","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3065-8498","authenticated-orcid":true,"given":"Michael T.","family":"Chin","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8302-6796","authenticated-orcid":true,"given":"Navin K.","family":"Kapur","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Interventional Research Laboratories, and The Cardiovascular Center, Tufts Medical Center."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.005929"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.036691"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7245384"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.118.004905"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.06.062"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2307227"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2019.04.019"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.06.031"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.08.025"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00028.2018"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.07.005"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1341.022"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.07.005"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.11.007"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/jdb8020010"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12461"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000155"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv597"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.117.005805"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001052"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.01.069"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx414"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2017.02.028"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw145"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2015.06.010"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.05.034"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038269"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2022.08.011"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.10.017"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1177\/0267659112473172"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.122.010328"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2023.01.004"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.121.010537"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8090-8-163"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-02878-3"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2020.10.151"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.012094"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-01006-8"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2020.02.001"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.123.065298","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T22:48:52Z","timestamp":1748472532000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.123.065298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,23]]},"references-count":39,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2024,4,23]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.123.065298"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.123.065298","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,23]]},"assertion":[{"value":"2023-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}