The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) : multicenter pig study on the effect of ischemic preconditioning
Kleinbongard, Petra (University of Duisburg-Essen)
Arriola, C.G. (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Badimon, Lina (Institut de Recerca Sant Pau)
Crisóstomo, Verónica (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Giricz, Z. (Pharmahungary Group)
Gyöngyösi, M. (Medical University of Vienna)
Heusch, Gerd (University of Duisburg-Essen)
Ibañez, Borja (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Kiss, A. (Medical University of Vienna)
de Kleijn, D.P.V. (University Medical Center Utrecht)
Podesser, B.K. (Medical University of Vienna)
Ramírez Carracedo, Rafael (Universidad Francisco de Vitoria)
Rodríguez-Sinovas, A. (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Ruiz-Meana, M. (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Sanchez Margallo, F.M. (Centro de Cirugía de Mínima Invasión Jesús Usón)
Vilahur, Gemma (Institut de Recerca Sant Pau)
Zamorano, José Luis (Hospital Universitario Ramón y Cajal (Madrid))
Zaragoza, C. (Universidad Francisco de Vitoria)
Ferdinandy, Péter (Semmelweis University)
Hausenloy, D. J. (University College London)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Basic Research in Cardiology, Vol. 119 Núm. 6 (december 2024) , p. 893-909, ISSN 1435-1803

DOI: 10.1007/s00395-024-01083-9
PMID: 39422732

17 p, 1.6 MB

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