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

IF 7.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Basic Research in Cardiology Pub Date : 2024-10-18 DOI:10.1007/s00395-024-01083-9
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
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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.

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改善心脏保护疗法的临床前评估(IMPACT):关于缺血预处理效果的多中心猪研究
据报道,在临床前研究中,许多心脏保护干预措施都能缩小心肌梗死面积(IS)。然而,将这些干预措施转化为急性心肌梗死(AMI)患者的治疗效果却令人大失所望。缺乏转化的原因之一是临床前研究缺乏严谨性和可重复性。为了解决这个问题,我们建立了欧洲IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) pig AMI网络,该网络采用集中随机化和盲法核心实验室IS分析,并以缺血预处理(IPC)作为阳性对照对该网络进行了验证。COST创新者基金(IG16225)网络中的10个研究机构参与了IMPACT网络。通过对梗死图像的质量控制和使用预先定义的排除标准,最终分析排除了三家研究机构。通过集中生成的随机化列表,猪被分配到心肌缺血/再灌注(I/R,N = 5/站点)或IPC + I/R(N = 5/站点)。主要终点是IS[风险面积(AAR)百分比],由集中、盲法核心实验室(5个研究点)的三苯基氯化四氮唑(TTC)染色量化;或IS[左心室质量(LV)百分比],由集中、盲法心脏磁共振(CMR)核心实验室(2个研究点)量化。在汇总分析中,与 I/R 相比,IPC 显著降低了 IS(57 ± 14 对 32 ± 19 [%AAR] N = 25 头猪/组;p < 0.001;25 ± 13 对 14 ± 8 [%LV]; N = 10 头猪/组;p = 0.021)。在特定部位的分析中,与 I/R 相比,在 5 个部位中的 4 个部位,通过 TTC 定量,IPC 能显著降低 IS;通过 CMR 定量,在 2 个部位中的 1 个部位,IPC 能显著降低 IS。建立并验证了一个猪 AMI 多中心欧洲网络,该网络采用集中随机化和核心盲法 IS 分析,旨在提高临床前研究中心脏保护干预措施的可重复性,并将心脏保护措施转化为对患者有益的措施。
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来源期刊
Basic Research in Cardiology
Basic Research in Cardiology 医学-心血管系统
CiteScore
16.30
自引率
5.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Basic Research in Cardiology is an international journal for cardiovascular research. It provides a forum for original and review articles related to experimental cardiology that meet its stringent scientific standards. Basic Research in Cardiology regularly receives articles from the fields of - Molecular and Cellular Biology - Biochemistry - Biophysics - Pharmacology - Physiology and Pathology - Clinical Cardiology
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