Petrusca Lorena, Croisille Pierre, Augeul Lionel, Ovize Michel, Mewton Nathan, Viallon Magalie
Univ Lyon, UJM-Saint-Etienne, INSA, CNRS UMR 5520, INSERM U1206, Saint-Etienne, France.
Department of Radiology, Centre Hospitalier Universitaire de Saint- Etienne, Université Jean-Monnet, Saint-Etienne, France.
Front Cardiovasc Med. 2023 Apr 27;10:1134389. doi: 10.3389/fcvm.2023.1134389. eCollection 2023.
Cardioprotection strategies remain a new frontier in treating acute myocardial infarction (AMI), aiming at further protect the myocardium from the ischemia-reperfusion damage. Therefore, we aimed at investigating the mechano-transduction effects induced by shock waves (SW) therapy at time of the ischemia reperfusion as a non-invasive cardioprotective innovative approach to trigger healing molecular mechanisms.
We evaluated the SW therapy effects in an open-chest pig ischemia-reperfusion (IR) model, with quantitative cardiac Magnetic Resonance (MR) imaging performed along the experiments at multiple time points (baseline (B), during ischemia (I), at early reperfusion (ER) (∼15 min), and late reperfusion (LR) (3 h)). AMI was obtained by a left anterior artery temporary occlusion (50 min) in 18 pigs (32 ± 1.9 kg) randomized into SW therapy and control groups. In the SW therapy group, treatment was started at the end of the ischemia period and extended during early reperfusion (600 + 1,200 shots @0.09 J/mm2, f = 5 Hz). The MR protocol included at all time points LV global function assessment, regional strain quantification, native T1 and T2 parametric mapping. Then, after contrast injection (gadolinium), we obtained late gadolinium imaging and extra-cellular volume (ECV) mapping. Before animal sacrifice, Evans blue dye was administrated after re-occlusion for area-at-risk sizing.
During ischemia, LVEF decreased in both groups (25 ± 4.8% in controls ( = 0.031), 31.6 ± 3.2% in SW ( = 0.02). After reperfusion, left ventricular ejection fraction (LVEF) remained significantly decreased in controls (39.9 ± 4% at LR vs. 60 ± 5% at baseline ( = 0.02). In the SW group, LVEF increased quickly ER (43.7 ± 11.4% vs. 52.4 ± 8.2%), and further improved at LR (49.4 ± 10.1) (ER vs. LR = 0.05), close to baseline reference (LR vs. B = 0.92). Furthermore, there was no significant difference in myocardial relaxation time (i.e. edema) after reperfusion in the intervention group compared to the control group: T1 (MI vs. remote) was increased by 23.2±% for SW vs. +25.2% for the controls, while T2 (MI vs. remote) increased by +24.9% for SW vs. +21.7% for the control group.
In conclusion, we showed in an ischemia-reperfusion open-chest swine model that SW therapy, when applied near the relief of 50' LAD occlusion, led to a nearly immediate cardioprotective effect translating to a reduction in the acute ischemia-reperfusion lesion size and to a significant LV function improvement. These new and promising results related to the multi-targeted effects of SW therapy in IR injury need to be confirmed by further in-vivo studies in close chest models with longitudinal follow-up.
心脏保护策略仍是治疗急性心肌梗死（AMI）的新领域，旨在进一步保护心肌免受缺血再灌注损伤。因此，我们旨在研究冲击波（SW）疗法在缺血再灌注时诱导的机械转导效应，作为一种触发愈合分子机制的非侵入性心脏保护创新方法。
我们在开胸猪缺血再灌注（IR）模型中评估了SW疗法的效果，在多个时间点（基线（B）、缺血期间（I）、早期再灌注（ER）（约15分钟）和晚期再灌注（LR）（3小时））进行定量心脏磁共振（MR）成像。通过左前动脉临时闭塞（50分钟）在18头猪（32±1.9千克）中诱导AMI，将其随机分为SW治疗组和对照组。在SW治疗组中，治疗在缺血期结束时开始，并在早期再灌注期间进行（600 + 1200次冲击，能量密度为0.09 J/mm2，频率f = 5 Hz）。MR方案在所有时间点包括左心室整体功能评估、区域应变量化、固有T1和T2参数映射。然后，在注射造影剂（钆）后，我们获得延迟钆增强成像和细胞外容积（ECV）映射。在动物处死前，再次闭塞后给予伊文思蓝染料以确定梗死面积。
在缺血期间，两组左心室射血分数（LVEF）均下降（对照组为25±4.8%（P = 0.031），SW组为31.6±3.2%（P = 0.02））。再灌注后，对照组左心室射血分数（LVEF）仍显著下降（LR时为39.9±4%，而基线时为60±5%（P = 0.02））。在SW组中，LVEF在ER时迅速增加（43.7±11.4%对52.4±8.2%），并在LR时进一步改善（49.4±10.1）（ER对LR，P = 0.05），接近基线参考值（LR对B，P = 0.92）。此外，与对照组相比，干预组再灌注后心肌弛豫时间（即水肿）无显著差异：SW组T1（梗死心肌与远隔心肌）增加23.2±%，对照组增加25.2%，而SW组T2（梗死心肌与远隔心肌）增加24.9%，对照组增加21.7%。
总之，我们在缺血再灌注开胸猪模型中表明，当在左前降支闭塞50分钟解除时应用SW疗法，可导致近乎即时的心脏保护作用，转化为急性缺血再灌注损伤面积减小和左心室功能显著改善。这些与SW疗法在IR损伤中的多靶点效应相关的新的有前景的结果需要通过在闭合胸腔模型中进行进一步的体内研究并进行纵向随访来证实。
