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oai:repisalud.isciii.es:20.500.12105/258252025-12-18T13:00:38Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Kleinbongard, Petra author Arriola, Carlos Galán author Badimon, Lina author Crisostomo, Veronica author Giricz, Zoltán author Gyöngyösi, Mariann author Heusch, Gerd author Ibanez, Borja author Kiss, Attila author de Kleijn, Dominique P V author Podesser, Bruno K author Carracedo, Rafael Ramírez author Rodríguez-Sinovas, Antonio author Ruiz-Meana, Marisol author Sanchez Margallo, Francisco M author Vilahur, Gemma author Zamorano, José Luis author Zaragoza, Carlos author Ferdinandy, Peter author Hausenloy, Derek J author 2024-10-18 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 = 5/site) or IPC + I/R (N = 5/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 ± 14 versus 32 ± 19 [%AAR] N = 25 pigs/group; p < 0.001; 25 ± 13 versus 14 ± 8 [%LV]; N = 10 pigs/group; p = 0.021). 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. Basic Res Cardiol. 2024 Oct 18. Basic Research in Cardiology 39422732 https://hdl.handle.net/20.500.12105/25825 Acute myocardial infarction Ischemia/reperfusion injury Ischemic preconditioning Multicenter network Pig Randomized-controlled trial The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): multicenter pig study on the effect of ischemic preconditioning.