Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study,Basic Research in Cardiology

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Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study
Basic Research in Cardiology ( IF 9.5 ) Pub Date : 2021-02-06 , DOI: 10.1007/s00395-021-00851-1
Ignatios Ikonomidis ₁ , Dimitrios Vlastos _{1,

2} , Ioanna Andreadou ₃ , Maria Gazouli ₄ , Panagiotis Efentakis ₃ , Maria Varoudi ₁ , George Makavos ₁ , Alkistis Kapelouzou ₅ , John Lekakis ₁ , John Parissis ₁ , Spiridon Katsanos ₁ , Damianos Tsilivarakis ₁ , Derek J Hausenloy _{6,

7,

8,

9,

10} , Dimitrios Alexopoulos ₁ , Dennis V Cokkinos ₅ , Hans-Eric Bøtker ₁₁ , Efstathios K Iliodromitis ₁

Affiliation

2nd Department of Cardiology, Medical School, Attikon Hospital, National and Kapodistrian University of Athens, Rimini 1, Haidari, 12462, Athens, Greece.
Department of Cardiac Surgery, Royal Brompton Hospital, London, UK.
Laboratory of Pharmacology, School of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.
Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Biomedical Research Foundation, Academy of Athens, Athens, Greece.
National Heart Centre, National Heart Research Institute Singapore, Singapore, Singapore.
Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.
The Hatter Cardiovascular Institute, University College London, London, UK.
The National Institute of Health Research University College London Hospitals Biomedical Research Centre, Research and Development, London, UK.
Centro de Biotecnologia-FEMSA, Tecnologico de Monterrey, Monterrey, Mexico.
Department of Cardiology, Aarhus University Hospital Skejby, Aarhus N, Denmark.

Aims

Remote ischemic conditioning (RIC) alleviates ischemia–reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection.

Methods and results

We block-randomised 270 patients within 48 h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: (a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity; (b) the carotid-femoral pulse wave velocity (PWV); (c) miR-144,-150,-21,-208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40 min after RIC onset (T3); and (d) LV volumes at baseline and after one year. Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p < 0.05) at T3 following single- than double-cycle inflation (PBR:ΔT0–T3 = 0.249 ± 0.033 vs 0.126 ± 0.034 μm, p = 0.03 and PWV:0.4 ± 0.21 vs −1.02 ± 0.24 m/s, p = 0.03). Increased miR-150,-21,-208 (p < 0.05) and reduced MDA was observed after both protocols. Increased miR-144 was related to PWV reduction (r = 0.763, p < 0.001) after the first-cycle inflation in both protocols. After one year, single-cycle RIC was associated with LV end-systolic volume reduction (LVESV) > 15% (odds-ratio of 3.75, p = 0.029). MiR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r = 0.40 and 0.37, p < 0.05), in the single-cycle RIC.

Conclusion

RIC evokes “vascular conditioning” likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling.

Clinical Trial Registration

http://www.clinicaltrials.gov. Unique identifier: NCT03984123.

中文翻译：

血管调理可预防急性心肌梗死后左心室不良重构：一项随机远程调理研究

目标

远程缺血调理 (RIC) 通过多种途径减轻缺血再灌注损伤，包括微 RNA (miR) 表达和氧化应激调节。我们研究了 RIC 对内皮糖萼、动脉僵硬度、LV 重塑以及作为保护目标的脉管系统内的潜在介质的影响。

方法和结果

我们在 PCI 后 STEMI 后 48 小时内对 270 名患者进行了随机分组，使其接受一个或两个周期的双侧臂袖充气，以及一个没有 RIC 的对照组。我们测量了：（a）舌下动脉微血管的灌注边界区域（PBR），以评估糖萼的完整性；(b) 颈股动脉脉搏波速度 (PWV)；(c) 基线 (T0) 和 RIC 发作后 40 分钟 (T3) 的 miR-144、-150、-21、-208、硝酸盐-亚硝酸盐 (NOx) 和丙二醛 (MDA) 血浆水平；(d) 基线时和一年后的 LV 体积。与基线相比，单周期充气比双周期充气后 T3的 PBR 和 PWV 下降幅度更大，miR-144 和 NOx 水平增加（ p < 0.05）（PBR：ΔT0–T3 = 0.249 ± 0.033 vs 0.126 ± 0.034 μm , p = 0.03 和 PWV:0.4 ± 0.21 vs -1.02 ± 0.24 m/s,p = 0.03)。两种方案后均观察到miR-150,-21,-208 ( p < 0.05) 增加和 MDA 减少。增加的 miR-144 与两种方案的第一周期膨胀后PWV 降低有关 ( r = 0.763, p < 0.001)。一年后，单周期 RIC 与 LV 收缩末期容积减少 (LVESV) > 15% 相关（优势比为 3.75，p = 0.029）。在单周期 RIC 中，RIC 后 MiR-144 和 PWV 变化相互关联，并与随访时 LVESV 降低相关（r = 0.40 和 0.37，p < 0.05）。