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Many interventions have been investigated to offer additional protection. One such intervention is remote ischaemic conditioning (RIC) involving short-episodes of ischaemia of the arm with a blood pressure cuff, followed by reperfusion to protect the heart organs from subsequent severe ischaemia. However, the recent CONDI2-ERIC-PPCI multicentre study of RIC in STEMI showed no benefit in clinical outcome in low risk patients. It could also be argued that these patients were already in a partially protected state, highlighting the disconnect between animal- and clinical-based outcome studies. To improve potential translatability, we developed an animal model using pharmacological agents similar to those given to patients presenting with an AMI, prior to PPCI. Rats underwent MI on a combined background of an opioid agonist, heparin and a platelet-inhibitor thereby allowing us to assess whether additional cardioprotective strategies had any effect over and above this \u201ccocktail\u201d. We demonstrated that the \u201cbackground drugs\u201d were protective in their own right, reducing MI from 57.5\u2009\u00b1\u20093.7% to 37.3\u2009\u00b1\u20092.9% (<jats:italic>n<\/jats:italic>\u2009=\u200911, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). On this background of drugs, RIC did not add any further protection (38.0\u2009\u00b1\u20093.4%). However, using a caspase inhibitor, which acts via a different mechanistic pathway to RIC, we were able to demonstrate additional protection (20.6\u2009\u00b1\u20093.3%). This concept provides initial evidence to develop models which can be used to evaluate future animal-to-clinical translation in cardioprotective studies.<\/jats:p>","DOI":"10.1007\/s00395-020-00830-y","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T19:02:48Z","timestamp":1605294168000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The importance of clinically relevant background therapy in cardioprotective studies"],"prefix":"10.1007","volume":"115","author":[{"given":"Zhenhe","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-4980","authenticated-orcid":false,"given":"Sean M.","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7791-9320","authenticated-orcid":false,"given":"Derek M.","family":"Yellon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,13]]},"reference":[{"key":"830_CR1","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1007\/s00395-018-0692-z","volume":"113","author":"JP Audia","year":"2018","unstructured":"Audia JP, Yang XM, Crockett ES, Housley N, Haq EU, O\u2019Donnell K, Cohen MV, Downey JM, Alvarez DF (2018) Caspase-1 inhibition by VX-765 administered at reperfusion in P2Y12 receptor antagonist-treated rats provides long-term reduction in myocardial infarct size and preservation of ventricular function. 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