The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): multicenter pig study on the effect of ischemic preconditioning
Year: 2024
Type: article
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.
Source: Basic Research in Cardiology
Authors: Petra Kleinbongard, Carlos Galán Arriola, Lina Badimon, Veronica Crisostomo, Zoltán Giricz, Mariann Gyöngyösi, Gerd Heusch, Borja Ibanez, Attila Kiss, Dominique P. V. de Kleijn, Bruno K. Podesser, Rafael Ramírez Carracedo, Antonio Rodríguez-Sinovas, Marisol Ruiz-Meana, Francisco M. Sanchez Margallo, Gemma Vilahur, José Luis Zamorano, Carlos Zaragoza, Peter Ferdinandy, Derek J. Hausenloy
Institutions: West German Heart and Vascular Center Essen, University of Duisburg-Essen, Spanish National Centre for Cardiovascular Research, Centro de Investigación en Red en Enfermedades Cardiovasculares, Centro de Investigación Biomédica en Red, Hospital de Sant Pau, Instituto de Salud Carlos III, Centro de Cirugía de Mínima Invasión Jesús Usón, Semmelweis University, Pharmahungary Group (Hungary), Medical University of Vienna, Ludwig Boltzmann Institute for Cardiovascular Research, University Medical Center Utrecht, Universidad Francisco de Vitoria, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, National University of Singapore, Duke-NUS Medical School, National Heart Centre Singapore, University College London
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
Funders: 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
Awards: G1493173353, G1602493886, G1728342668, G1855990336, G2028378607, G2152959462, G2262748287, G2309174360, G245083819, G2490703178, G2536561372, G2672435700, G2845063680, G288011245, G300979063, G3480869486, G425668148, G430777504, G4611434993, G4766918145, G5080475149, G5421974903, G542540857, G5764717880, G5953545561, G7940339510, G8416764847
OpenAlex ID: W4403542177