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.

在临床前研究中，据报道，许多心脏保护干预措施可减少心肌梗死面积 （IS）。然而，他们为急性心肌梗死 （AMI） 患者的利益而进行的翻译在很大程度上令人失望。缺乏翻译的一个原因是临床前研究缺乏严谨性和可重复性。为了解决这个问题，我们建立了欧洲心脏保护疗法临床前评估 （IMPACT） 猪 AMI 网络，具有集中随机化和盲法核心实验室 IS 分析，并以缺血预处理 （IPC） 作为阳性对照验证了该网络。COST Innovators Grant （IG16225） 网络中的 10 个站点参与了 IMPACT 网络。通过对梗死图像进行质量控制和使用预定义的排除标准，将 3 个部位排除在最终分析之外。使用集中生成的随机化列表，将猪分配到心肌缺血/再灌注 （I/R，N = 5/部位） 或 IPC + I/R （N = 5/部位）。主要终点是 IS [% risk-area-at-risk （AAR）]，在集中盲法核心实验室（5 个地点）通过三苯基-四唑氯化物 （TTC） 染色量化，或 IS [% 左心室质量 （LV）]，由集中盲法心脏磁共振 （CMR） 核心实验室（2 个地点）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;13 ± 25 vs 8 ± 14 [%LV];N = 10 头猪/组;p = 0.021）。在位点特异性分析中，与 I/R 相比，IPC 在 TTC 定量的 4 个位点中，在 2 个位点中的 1 个位点通过 CMR 定量时显著降低了 IS。 建立并验证了具有集中随机化和核心盲法 IS 分析的猪 AMI 多中心欧洲网络，旨在提高临床前研究中心脏保护干预的可重复性以及心脏保护为患者利益的转化。