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A major factor is the lack of rigor and reproducibility in the preclinical studies. To address this, we have established the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) small animal multisite acute myocardial infarction (AMI) network, with centralized randomization and blinded core laboratory IS analysis, and have validated the network using ischemic preconditioning (IPC). Eight sites from the COST Innovators Grant (IG16225) network participated in the IMPACT AMI study. Mice and rats were randomly allocated into Sham, Control, or IPC groups. The IRI group underwent 45\u00a0min (mice) or 30\u00a0min (rats) of left coronary artery occlusion followed by 24\u00a0h reperfusion. IPC comprised three cycles of 5\u00a0min occlusion\/reperfusion before IRI. IS was determined by a blinded core lab. The majority of site showed significant cardioprotection with IPC. In pooled mouse data, IPC (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200942) reduced IS\/AAR by 35% compared to control (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200948) (30\u2009\u00b1\u200916% versus 46\u2009\u00b1\u200913%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.005), and in rat data, IPC (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200936) reduced IS\/AAR by 29% when compared to control (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200939) (32\u2009\u00b1\u200919% versus 45\u2009\u00b1\u200914%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). The IMPACT multisite mouse and rat AMI networks, with centralized randomization and blinded core IS analysis, were established to improve the reproducibility of cardioprotective interventions in preclinical studies and to facilitate the translation of these therapies for patient benefit.\n                  <\/jats:p>","DOI":"10.1007\/s00395-025-01102-3","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:25:57Z","timestamp":1741764357000},"page":"335-346","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): a small animal acute myocardial infarction randomized-controlled multicenter study on the effect of ischemic 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Brenner, Andr\u00e1s Makkos, Tam\u00e1s G. Gergely and Nabil V. Sayour were missing from the author group due to an administrative error on the authors\u2019 part.","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2025","order":9,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":10,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":11,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s00395-025-01142-9","URL":"https:\/\/doi.org\/10.1007\/s00395-025-01142-9","order":12,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"TK is Chief Medical Officer and Founder of Camoxis Ltd. TK and HAP are in part funded by the British Heart Foundation. P.F. is the founder and CEO, and ZG is involved in the management of Pharmahungary Group, a group of R&D companies. DJH has received: consultant fees from Faraday Pharmaceuticals Inc. and Boehringer Ingelheim International GmbH; honoraria from Servier; and research funding from Astra Zeneca, Merck Sharp & Dohme Corp and Novonordisk. All other authors declare no competing interests. In case of industrial interest, Pharmahungary Group will organize multicenter studies involving the selected and validated sites of the current COST action (IG16225) according to the COST action final report.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}