{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T12:48:40Z","timestamp":1768999720991,"version":"3.49.0"},"reference-count":51,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CSIRO SIEF STEM+","award":["Business Fellowship"],"award-info":[{"award-number":["Business Fellowship"]}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1125392"],"award-info":[{"award-number":["1125392"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Reperfusion therapy increases survival post-acute myocardial infarction (AMI) while also stimulating secondary oxidant production and immune cell infiltration. Neutrophils accumulate within infarcted myocardium within 24 h post-AMI and release myeloperoxidase (MPO) that catalyses hypochlorous acid (HOCl) production while increasing oxidative stress and inflammation, thereby enhancing ventricular remodelling. Nitroxides inhibit MPO-mediated HOCl production, potentially ameliorating neutrophil-mediated damage. Aim: Assess the cardioprotective ability of nitroxide 4-methoxyTEMPO (4MetT) within the setting of AMI. Methods: Male Wistar rats were separated into 3 groups: SHAM, AMI\/R, and AMI\/R + 4MetT (15 mg\/kg at surgery via oral gavage) and subjected to left descending coronary artery ligation for 30 min to generate an AMI, followed by reperfusion. One cohort of rats were sacrificed at 24 h post-reperfusion and another 28 days post-surgery (with 4MetT (15 mg\/kg) administration twice daily). Results: 3-chlorotyrosine, a HOCl-specific damage marker, decreased within the heart of animals in the AMI\/R + 4-MetT group 24 h post-AMI, indicating the drug inhibited MPO activity; however, there was no evident difference in either infarct size or myocardial scar size between the groups. Concurrently, MPO, Nf\u03baB, TNF\u03b1, and the oxidation marker malondialdehyde increased within the hearts, with 4-MetT only demonstrating a trend in decreasing MPO and TNF levels. Notably, 4MetT provided a significant improvement in cardiac function 28 days post-AMI, as assessed by echocardiography, indicating potential for 4-MetT as a treatment option, although the precise mechanism of action of the compound remains unclear.<\/jats:p>","DOI":"10.3390\/ijms21207650","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T08:56:48Z","timestamp":1602838608000},"page":"7650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nitroxides Mitigate Neutrophil-Mediated Damage to the Myocardium after Experimental Myocardial Infarction in Rats"],"prefix":"10.3390","volume":"21","author":[{"given":"Mary","family":"El Kazzi","sequence":"first","affiliation":[{"name":"Discipline of Pathology, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney 2006 NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Shi","sequence":"additional","affiliation":[{"name":"Discipline of Pathology, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney 2006 NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2295-7893","authenticated-orcid":false,"given":"Sally","family":"Vuong","sequence":"additional","affiliation":[{"name":"Heart Research Institute, Sydney Medical School, The University of Sydney, Sydney 2006 NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaosuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Discipline of Pathology, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney 2006 NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Belal","family":"Chami","sequence":"additional","affiliation":[{"name":"Discipline of Pathology, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney 2006 NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Discipline of Pathology, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney 2006 NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3446-2241","authenticated-orcid":false,"given":"Benjamin S.","family":"Rayner","sequence":"additional","affiliation":[{"name":"Heart Research Institute, Sydney Medical School, The University of Sydney, Sydney 2006 NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2237-7004","authenticated-orcid":false,"given":"Paul K.","family":"Witting","sequence":"additional","affiliation":[{"name":"Discipline of Pathology, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney 2006 NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1161\/CIRCULATIONAHA.112.128413","article-title":"Estimating deaths from cardiovascular disease: A review of global methodologies of mortality measurement","volume":"127","author":"Pagidipati","year":"2013","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1136\/hrt.53.4.363","article-title":"Plaque fissuring\u2014The cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina","volume":"53","author":"Davies","year":"1985","journal-title":"Br. 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