The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): multicenter pig study on the effect of ischemic preconditioning

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.

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Publication Details

Journal
Basic Research in Cardiology
Published
2024-10-18
DOI
https://doi.org/10.1007/s00395-024-01083-9
Citations
18
Primary Topic
Cardiac Ischemia and Reperfusion
Type
article
Field-Weighted Citation Impact
7.65

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article

The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): multicenter pig study on the effect of ischemic preconditioning

Carlos Galán‐Arriola, Lina Badimón, Derek J. Hausenloy, Attila Kiss et al.
18 citations
Basic Research in Cardiology
Cardiac Ischemia and Reperfusion
7.65
article

The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): multicenter pig study on the effect of ischemic preconditioning

Carlos Galán‐Arriola, Lina Badimón, Derek J. Hausenloy, Attila Kiss, Borja Ibáñez, Péter Ferdinandy, Carlos Zaragoza, Marisol Ruiz‐Meana, Rafael Ramírez-Carracedo, Bruno Karl Podesser, Verónica Crisóstomo, Petra Kleinbongard, Dominique P.V. de Kleijn, Zoltán Giricz, Gerd Heusch, Francisco M. Sánchez‐Margallo, Mariann Gyöngyösi, Gemma Vilahur, Antonio Rodríguez‐Sinovas, José Luís Zamorano
article en
18 citations

Abstract

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 Research in CardiologyVol. 119(6)
Semmelweis University (HU), National University of Singapore (SG), University of Szeged (HU), Universidad Francisco de Vitoria (ES), Instituto de Salud Carlos III (ES), Spanish National Centre for Cardiovascular Research (ES), University Medical Center Utrecht (NL), Centro de Investigación en Red en Enfermedades Cardiovasculares (ES), Centro de Cirugía de Mínima Invasión Jesús Usón (ES), Vall d'Hebron Institut de Recerca (ES), Centro de Investigación Biomédica en Red (ES), Duke-NUS Medical School (SG), Instituto Ramón y Cajal de Investigación Sanitaria (ES), Spanish National Centre for Cardiovascular Research (ES), National Heart Centre Singapore (SG), Hospital Universitario Ramón y Cajal (ES), West German Heart and Vascular Center Essen (DE), University College London (GB), University of Duisburg-Essen (DE), Medical University of Vienna (AT)
Duke-NUS Medical School, Universitätsklinikum Essen, Aromatic Plant Research Center, Deutsche Forschungsgemeinschaft, Hungarian Scientific Research Fund, Ministerio de Ciencia e Innovación, Centro Nacional de Investigaciones Cardiovasculares, Innovációs és Technológiai Minisztérium, Ludwig Boltzmann Gesellschaft, EU-CARDIOPROTECTION, Medical Research Council, National Medical Research Council, Instituto de Salud Carlos III, Agencia Estatal de Investigación
Reduced inequalities
Openalex Percentile: Top 2%
Cardiac Ischemia and Reperfusion
7.65
DOIOpen Access PDFOpenAlex
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