{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:11:04Z","timestamp":1790655064024,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["JP22K08965"],"award-info":[{"award-number":["JP22K08965"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p\/>\n               <jats:sec>\n                  <jats:title>OBJECTIVES<\/jats:title>\n                  <jats:p>In myocardial infarction, the addition of mineralocorticoid receptor blockers to standard therapies, such as angiotensin-converting enzyme inhibitors or beta-blockers, reportedly reduces mortality and cardiac events. We investigated whether the non-steroidal mineralocorticoid receptor blocker esaxerenone has cardioprotective effects and its protective mechanisms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Isolated rat hearts were Langendorff-perfused (constant pressure, 80\u2009mmHg) with oxygenated Krebs\u2013Henseleit bicarbonate buffer and reperfused for 60\u2009min; afterwards, recovery of function (left ventricular pressure, measured with an intraventricular balloon) and myocardial injury were measured. In a preliminary study, we determined the optimal concentration of esaxerenone required for myocardial protection. Next, esaxerenone was administered in the pre- and post-ischaemic phases to determine the optimal timing of administration. In addition, we assessed coronary flow response to acetylcholine with and without esaxerenone. We examined whether esaxerenone-induced cardioprotection was prevented by targeting putative components in the preconditioning manner (the mitochondrial ATP-sensitive potassium [KATP] channel).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Myocardial protection by esaxerenone was observed when esaxerenone was administered before ischaemia but not after ischaemia. The coronary flow response to acetylcholine was significantly better in the esaxerenone group than in the control group. The cardioprotective effect of esaxerenone was eliminated by the mitochondrial KATP channel blocker, 5-hydroxy decanoate.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>This study confirmed the myocardial protective effect of the pre-ischaemic administration of esaxerenone. Esaxerenone may contribute to coronary endothelial protection and exert pharmacological preconditioning via the mitochondrial KATP channel.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejcts\/ezad405","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T22:34:52Z","timestamp":1701988492000},"source":"Crossref","is-referenced-by-count":5,"title":["Effect of esaxerenone on ischaemia and reperfusion injury in rat hearts"],"prefix":"10.1093","volume":"64","author":[{"given":"Hiromasa","family":"Yamashita","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4678-8502","authenticated-orcid":false,"given":"Masahiro","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuzo","family":"Bessho","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-0394","authenticated-orcid":false,"given":"Yosuke","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Nippon Medical School , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,7]]},"reference":[{"key":"2023121612033810700_ezad405-B1","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"},{"key":"2023121612033810700_ezad405-B2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/MED.0b013e3283391989","article-title":"Aldosterone and inflammation","volume":"17","author":"Gilbert","year":"2010","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"2023121612033810700_ezad405-B3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10741-005-2348-y","article-title":"The mineralocorticoid receptor and oxidative stress","volume":"10","author":"Fiebeler","year":"2005","journal-title":"Heart Fail Rev"},{"key":"2023121612033810700_ezad405-B4","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1097\/MNH.0b013e3282f56854","article-title":"Mechanisms of mineralocorticoid receptor-mediated cardiac fibrosis and vascular inflammation","volume":"17","author":"Young","year":"2008","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"2023121612033810700_ezad405-B5","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1161\/01.CIR.88.5.2277","article-title":"Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dilatation in patients with asymptomatic systolic dysfunction. 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