The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): multicenter pig study on the effect of ischemic preconditioning
Por:
Kleinbongard, P, Arriola, CG, Badimon, L, Crisostomo, V, Giricz, Z, Gyöngyösi, M, Heusch, G, Ibanez, B, Kiss, A, de Kleijn, DPV, Podesser, BK, Carracedo, RR, Rodríguez-Sinovas, A, Ruíz-Meana, M, Margallo, FMS, Vilahur, G, Zamorano, JL, Zaragoza, C, Ferdinandy, P, Hausenloy, DJ
Publicada:
18 oct 2024
Ahead of Print:
1 oct 2024
Resumen:
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.
Filiaciones:
Kleinbongard, P:
Univ Duisburg Essen, Univ Essen Med Sch, Inst Pathophysiol, West German Heart & Vasc Ctr, Hufelandstr 55, D-45122 Essen, Germany
Arriola, CG:
Ctr Nacl Invest Cardiovasc Carlos III, CIBER Enfermedades Cardiovasc CIBERCV, Melchor Fernandez Almagro 9, Madrid 28029, Spain
Badimon, L:
Res Inst Hosp Santa Creu & St Pau IIB St Pau, Barcelona, Spain
CIBER Enfermedades Cardiovasc, Barcelona, Spain
Crisostomo, V:
Jesus Uson Minimally Invas Surg Ctr CCMIJU, Cardiovasc Area, Caceres, Spain
ISCIII, RICORS TERAV Network, CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Giricz, Z:
Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, Cardiovasc & Metab Res Grp, Budapest, Hungary
Pharmahungary Grp, Szeged, Hungary
Gyöngyösi, M:
Med Univ Vienna, Dept Internal Med 2, Div Cardiol, A-1090 Vienna, Austria
Heusch, G:
Univ Duisburg Essen, Univ Essen Med Sch, Inst Pathophysiol, West German Heart & Vasc Ctr, Hufelandstr 55, D-45122 Essen, Germany
Ibanez, B:
Ctr Nacl Invest Cardiovasc CNIC, Madrid, Spain
Kiss, A:
Med Univ Vienna, Ludwig Boltzmann Inst Cardiovasc Res, Ctr Biomed Res & Translat Surg, Vienna, Austria
de Kleijn, DPV:
Univ Med Ctr Utrecht, Dept Vasc Surg, Utrecht, Netherlands
Podesser, BK:
Med Univ Vienna, Ludwig Boltzmann Inst Cardiovasc Res, Ctr Biomed Res & Translat Surg, Vienna, Austria
Carracedo, RR:
Univ Francisco Vitoria, Hosp Ramon & Cajal IRYCIS, Dept Cardiol, Unidad Invest Cardiovasc, Madrid, Spain
Rodríguez-Sinovas, A:
Hosp Univ Vall dHebron, Cardiovasc Dis Res Grp, Vall dHebron Inst Recerca VHIR, Passeig Vall dHebron 119-129, Barcelona 08035, Spain
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red Cardiovasc CIBERCV, ISCIII, Madrid, Spain
Ruíz-Meana, M:
Hosp Univ Vall dHebron, Cardiovasc Dis Res Grp, Vall dHebron Inst Recerca VHIR, Passeig Vall dHebron 119-129, Barcelona 08035, Spain
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red Cardiovasc CIBERCV, ISCIII, Madrid, Spain
Margallo, FMS:
Jesus Uson Minimally Invas Surg Ctr CCMIJU, Caceres, Spain
Vilahur, G:
Res Inst Hosp Santa Creu & St Pau IIB St Pau, Barcelona, Spain
Zamorano, JL:
Univ Hosp Ramon & Cajal, Madrid, Spain
Zaragoza, C:
Univ Francisco Vitoria, Hosp Ramon & Cajal IRYCIS, Dept Cardiol, Unidad Invest Cardiovasc, Madrid, Spain
Ferdinandy, P:
Pharmahungary Grp, Szeged, Hungary
Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, Nagyvarad Ter 4, H-1089 Budapest, Hungary
Semmelweis Univ, Ctr Pharmacol & Drug Res & Dev, Budapest, Hungary
Hausenloy, DJ:
Duke NUS Med Sch, Cardiovasc & Metab Disorders Program, 8 Coll Rd, Singapore 169857, Singapore
Natl Heart Res Inst Singapore, Natl Heart Ctr, Singapore, Singapore
Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore, Singapore
UCL, Hatter Cardiovasc Inst, London, England
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