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Gesellschaft","doi-asserted-by":"publisher","award":["CARREM"],"award-info":[{"award-number":["CARREM"]}],"id":[{"id":"10.13039\/501100016168","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017590","name":"Universit\u00e4tsklinikum Essen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017590","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Basic Res Cardiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Numerous cardioprotective interventions have been reported to reduce myocardial infarct size (IS) in pre-clinical studies. However, their translation for the benefit of patients with acute myocardial infarction (AMI) has been largely disappointing. One reason for the lack of translation is the lack of rigor and reproducibility in pre-clinical studies. To address this, we have established the European IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) pig AMI network with centralized randomization and blinded core laboratory IS analysis and validated the network with ischemic preconditioning (IPC) as a positive control. Ten sites in the COST Innovators Grant (IG16225) network participated in the IMPACT network. Three sites were excluded from the final analysis through quality control of infarct images and use of pre-defined exclusion criteria. Using a centrally generated randomization list, pigs were allocated to myocardial ischemia\/reperfusion (I\/R,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20095\/site) or IPC\u2009+\u2009I\/R (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20095\/site). The primary endpoint was IS [% area-at-risk (AAR)], as quantified by triphenyl-tetrazolium-chloride (TTC) staining in a centralized, blinded core laboratory (5 sites), or IS [% left-ventricular mass (LV)], as quantified by a centralized, blinded cardiac magnetic resonance (CMR) core laboratory (2 sites). In pooled analyses, IPC significantly reduced IS when compared to I\/R (57\u2009\u00b1\u200914 versus 32\u2009\u00b1\u200919 [%AAR]\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200925 pigs\/group;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001; 25\u2009\u00b1\u200913 versus 14\u2009\u00b1\u20098 [%LV];\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200910 pigs\/group;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.021). In site-specific analyses, in 4 of the 5 sites, IS was significantly reduced by IPC when compared to I\/R when quantified by TTC and in 1 of 2 sites when quantified by CMR. A pig AMI multicenter European network with centralized randomization and core blinded IS analysis was established and validated with the aim to improve the reproducibility of cardioprotective interventions in pre-clinical studies and the translation of cardioprotection for patient benefit.\n                  <\/jats:p>","DOI":"10.1007\/s00395-024-01083-9","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T09:02:33Z","timestamp":1729242153000},"page":"893-909","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): multicenter pig study on the effect of ischemic preconditioning"],"prefix":"10.1007","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3576-3772","authenticated-orcid":false,"given":"Petra","family":"Kleinbongard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-8974","authenticated-orcid":false,"given":"Carlos Gal\u00e1n","family":"Arriola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-2459","authenticated-orcid":false,"given":"Lina","family":"Badimon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1740-7029","authenticated-orcid":false,"given":"Veronica","family":"Crisostomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2036-8665","authenticated-orcid":false,"given":"Zolt\u00e1n","family":"Giricz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7083-2107","authenticated-orcid":false,"given":"Mariann","family":"Gy\u00f6ngy\u00f6si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7078-4160","authenticated-orcid":false,"given":"Gerd","family":"Heusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5036-254X","authenticated-orcid":false,"given":"Borja","family":"Ibanez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4652-1998","authenticated-orcid":false,"given":"Attila","family":"Kiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2714-2140","authenticated-orcid":false,"given":"Dominique P. 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Pharmahungary Group has a conflict of interest as it may be organizing multicenter studies on cardioprotection on external request and potentially including the here validated sites of the current COST action (IG16225). D.J.H. 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. J. L. Z. received speaker honoraria from Pfizer, Bayer, Novartis, and Amgem. All other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The experimental protocols conformed to the EU directive 2010\/63EU on the protection of animals used for scientific purposes and the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines [\n                      \n                      ]. The experimental protocols were formally approved by the appropriate national or institutional ethics committees (see Suppl. Data sheet experimental design).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statements"}}]}}