Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study

Abstract

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\xa0h 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\xa0min 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 \u2009<\u20090.05) at T3 following single- than double-cycle inflation (PBR:ΔT0–T3\u2009=\u20090.249\u2009±\u20090.033 vs 0.126\u2009±\u20090.034\xa0μm, p \u2009=\u20090.03 and PWV:0.4\u2009±\u20090.21 vs −1.02\u2009±\u20090.24\xa0m/s, p \u2009=\u20090.03). Increased miR-150,-21,-208 ( p \u2009<\u20090.05) and reduced MDA was observed after both protocols. Increased miR-144 was related to PWV reduction ( r \u2009=\u20090.763, p \u2009<\u20090.001) after the first-cycle inflation in both protocols. After one year, single-cycle RIC was associated with LV end-systolic volume reduction (LVESV)\u2009>\u200915% (odds-ratio of 3.75, p \u2009=\u20090.029). MiR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up ( r \u2009=\u20090.40 and 0.37, p \u2009<\u20090.05), 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.