IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): a small animal acute myocardial infarction randomized-controlled multicenter study on the effect of ischemic preconditioning

Although many cardioprotective interventions have been shown to limit infarct size (IS), in preclinical animal studies of acute myocardial ischemia/reperfusion injury (IRI), their clinical translation to patient benefit has been largely disappointing. A major factor is the lack of rigor and reproducibility in the preclinical studies. To address this, we have established the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) small animal multisite acute myocardial infarction (AMI) network, with centralized randomization and blinded core laboratory IS analysis, and have validated the network using ischemic preconditioning (IPC). Eight sites from the COST Innovators Grant (IG16225) network participated in the IMPACT AMI study. Mice and rats were randomly allocated into Sham, Control, or IPC groups. The IRI group underwent 45 min (mice) or 30 min (rats) of left coronary artery occlusion followed by 24 h reperfusion. IPC comprised three cycles of 5 min occlusion/reperfusion before IRI. IS was determined by a blinded core lab. The majority of site showed significant cardioprotection with IPC. In pooled mouse data, IPC (N = 42) reduced IS/AAR by 35% compared to control (N = 48) (30 ± 16% versus 46 ± 13%; p < 0.005), and in rat data, IPC (N = 36) reduced IS/AAR by 29% when compared to control (N = 39) (32 ± 19% versus 45 ± 14%; p < 0.01). The IMPACT multisite mouse and rat AMI networks, with centralized randomization and blinded core IS analysis, were established to improve the reproducibility of cardioprotective interventions in preclinical studies and to facilitate the translation of these therapies for patient benefit.

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Publication Details

Journal
Basic Research in Cardiology
Published
2025-03-12
DOI
https://doi.org/10.1007/s00395-025-01102-3
Citations
8
Primary Topic
Cardiac Ischemia and Reperfusion
Type
article
Field-Weighted Citation Impact
11.77

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article

IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): a small animal acute myocardial infarction randomized-controlled multicenter study on the effect of ischemic preconditioning

Ioanna Andreadou, Javier Inserte, Michał Ma̧czewski, Derek J. Hausenloy et al.
8 citations
Basic Research in Cardiology
Cardiac Ischemia and Reperfusion
11.77
article

IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): a small animal acute myocardial infarction randomized-controlled multicenter study on the effect of ischemic preconditioning

Ioanna Andreadou, Javier Inserte, Michał Ma̧czewski, Derek J. Hausenloy, Panagiotis Efentakis, Attila Kiss, Thomas Krieg, Coert J. Zuurbier, Pasquale Pagliaro, Róisín Kelly‐Laubscher, Marisol Ruiz‐Meana, Michał Waszkiewicz, Sauri Hernández‐Reséndiz, Brenda R. Kwak, Bruno Karl Podesser, Reinis Vilšķe̅rsts, Gary D. Lopaschuk, David Aluja, Marta Oknińska, Zoltán Giricz, Hiran A. Prag, Maija Dambrova, Tamara Szabados, Sandrine Lecour, Péter Ferdinandy, Péter Bencsik, Fei Gao
article en
8 citations

Abstract

Although many cardioprotective interventions have been shown to limit infarct size (IS), in preclinical animal studies of acute myocardial ischemia/reperfusion injury (IRI), their clinical translation to patient benefit has been largely disappointing. A major factor is the lack of rigor and reproducibility in the preclinical studies. To address this, we have established the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) small animal multisite acute myocardial infarction (AMI) network, with centralized randomization and blinded core laboratory IS analysis, and have validated the network using ischemic preconditioning (IPC). Eight sites from the COST Innovators Grant (IG16225) network participated in the IMPACT AMI study. Mice and rats were randomly allocated into Sham, Control, or IPC groups. The IRI group underwent 45 min (mice) or 30 min (rats) of left coronary artery occlusion followed by 24 h reperfusion. IPC comprised three cycles of 5 min occlusion/reperfusion before IRI. IS was determined by a blinded core lab. The majority of site showed significant cardioprotection with IPC. In pooled mouse data, IPC (N = 42) reduced IS/AAR by 35% compared to control (N = 48) (30 ± 16% versus 46 ± 13%; p < 0.005), and in rat data, IPC (N = 36) reduced IS/AAR by 29% when compared to control (N = 39) (32 ± 19% versus 45 ± 14%; p < 0.01). The IMPACT multisite mouse and rat AMI networks, with centralized randomization and blinded core IS analysis, were established to improve the reproducibility of cardioprotective interventions in preclinical studies and to facilitate the translation of these therapies for patient benefit.

Basic Research in CardiologyVol. 120(2)
Semmelweis University (HU), University of Geneva (CH), University of Alberta (CA), University of Cape Town (ZA), National University of Singapore (SG), National and Kapodistrian University of Athens (GR), University of Szeged (HU), University of Cambridge (GB), University College Cork (IE), Instituto de Salud Carlos III (ES), Centro de Investigación en Red en Enfermedades Cardiovasculares (ES), Latvijas Organiskās Sintēzes Institūts (LV), Vall d'Hebron Institut de Recerca (ES), Centro de Investigación Biomédica en Red (ES), Riga Stradiņš University (LV), Duke-NUS Medical School (SG), Postgraduate School of Molecular Medicine (PL), National Heart Centre Singapore (SG), Amsterdam University Medical Centers (NL), University College London (GB), University of Turin (IT), Medical University of Vienna (AT)
Duke-NUS Medical School, Aromatic Plant Research Center, Medical Research Council, National Medical Research Council, Instituto de Salud Carlos III
Good health and well-being
Openalex Percentile: Top 1%
Cardiac Ischemia and Reperfusion
11.77
DOIOpen Access PDFOpenAlex
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