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Understanding the associated pathophysiological mechanisms of cardiac dysfunction arising from ischaemic heart disease and the identification of sites for new therapeutic interventions requires a preclinical model that reproduces the key clinical characteristics of myocardial ischaemia, reperfusion and infarction. Here, we describe and validate a refined and minimally invasive translationally relevant approach to induce ischaemia, reperfusion and infarction in the sheep. The novelty and refinement in the procedure stems from utilization of implantable cardiac defibrillators prior to coronary engagement, balloon angioplasty to induce infarction, and intra\u2010operative anti\u2010arrhythmic drug protocols to reduce adverse arrhythmic events. The protocol is readily adoptable by researchers with access to standard fluoroscopic instrumentation, and it requires minimally invasive surgery. These refinements lead to a substantial reduction of intra\u2010operative mortality to 6.7% from previously published values ranging between 13% and 43%. The model produces key characteristics associated with the fourth universal definition of myocardial infarction, including ECG changes, elevated cardiac biomarkers and cardiac wall motility defects. In conclusion, the model closely replicates the clinical paradigm of myocardial ischaemia, reperfusion and infarction in a translationally relevant large animal setting, and the applied refinements reduce the incidence of intra\u2010operative mortality typically associated with preclinical myocardial infarction models.<\/jats:p>","DOI":"10.1113\/ep091760","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T06:39:47Z","timestamp":1734676787000},"page":"215-229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A refined, minimally invasive, reproducible ovine ischaemia\u2013reperfusion\u2013infarction model using implantable defibrillators: Methodology and validation"],"prefix":"10.1113","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7331-1326","authenticated-orcid":false,"given":"Charlene","family":"Pius","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Science, School of Medical Science, Faculty of Biology Medicine and Health, University of Manchester Manchester Academic Health Science Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9328-6452","authenticated-orcid":false,"given":"Barbara","family":"Niort","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Science, School of Medical Science, Faculty of Biology Medicine and Health, University of Manchester Manchester Academic Health Science Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8560-4812","authenticated-orcid":false,"given":"Emma J.","family":"Radcliffe","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Science, School of Medical Science, Faculty of Biology Medicine and Health, University of Manchester Manchester Academic Health Science Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2770-445X","authenticated-orcid":false,"given":"Andrew W.","family":"Trafford","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Science, School of Medical Science, Faculty of Biology Medicine and Health, University of Manchester Manchester Academic Health Science Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.09.020"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.12703\/P7-08"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.15420\/aer.2017.24.1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(01)02642-X"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.203984"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v9.i5.407"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303448"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0980703"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac053"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa575"},{"key":"e_1_2_9_12_1","first-page":"290","article-title":"Benefits of standardizing the treatment of arrhythmias in the sheep (Ovis aries) model of chronic heart failure after myocardial infarction","volume":"52","author":"Dardenne A.","year":"2013","journal-title":"Journal of the American Association for Laboratory Animal Science"},{"key":"e_1_2_9_13_1","unstructured":"Dasgupta A. &Wahed A.(2013).Clinical chemistry immunology and laboratory quality control: a comprehensive review for board preparation certification and clinical practice."},{"key":"e_1_2_9_14_1","first-page":"691","article-title":"The utility of troponin measurement to detect myocardial infarction: Review of the current findings","volume":"6","author":"Daubert M. 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