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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,5,19]]},"abstract":"<jats:p>Cardioplegia is often used prior to acquisition of human cardiac tissue to minimize warm ischemia time, which can severely confound studies of cardiac metabolism. However, there are several choices of cardioplegia solutions, and whether these solutions differentially impact tissue metabolism or metabolomic studies is not known. Here, we perform untargeted metabolomics, using both liquid chromatography\u2013mass spectrometry and gas chromatography\u2013mass spectrometry, on a large cohort of hearts transplanted for cardiomyopathy or from gift-of-life donors, and who have received different cardioplegia solutions. We show that different cardioplegia solutions distinctly impact cardiac metabolism and tissue metabolomic studies. Notably, these differences are mild relative to those seen comparing failing to nonfailing hearts, and identification of cardioplegia components in mass spectra should enable rigorous interpretation of changes between conditions. These data demonstrate how cardioplegia solutions may influence cardiac metabolism in human heart samples and underscore the need to report specific details of cardioplegia solution use in studies of human cardiac metabolism.<\/jats:p>","DOI":"10.1073\/pnas.2602039123","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T16:06:55Z","timestamp":1778170015000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Choice of cardioplegia influences metabolomics of human cardiac tissue"],"prefix":"10.1073","volume":"123","author":[{"given":"Sho","family":"Tanosaki","sequence":"first","affiliation":[{"name":"Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia"]},{"name":"Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia"]},{"name":"Department of Physiology, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of California","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Bedi","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia"]},{"name":"Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8093-4465","authenticated-orcid":false,"given":"Kenneth","family":"Margulies","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia"]},{"name":"Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Utah","place":["Salt Lake City"]},{"name":"Metabolomics Core Research Facility, University of Utah","place":["Salt Lake City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Arany","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia"]},{"name":"Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia"]},{"name":"Department of Physiology, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5290-0738","authenticated-orcid":false,"given":"E. Dale","family":"Abel","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of California","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318241"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.06.003"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.10.008"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.113.000404"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.12.003"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.123.004369"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2016.06.009"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.044452"},{"key":"e_1_3_4_9_2","first-page":"817","article-title":"Integrated landscape of cardiac metabolism in end-stage human nonischemic dilated cardiomyopathy","volume":"1","author":"Flam E.","year":"2022","unstructured":"E. Flam , Integrated landscape of cardiac metabolism in end-stage human nonischemic dilated cardiomyopathy. Nat. Cardiovasc. Res. 1, 817\u2013829 (2022).","journal-title":"Nat. Cardiovasc. 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