1. Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study.
- Author
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Ikonomidis I, Vlastos D, Andreadou I, Gazouli M, Efentakis P, Varoudi M, Makavos G, Kapelouzou A, Lekakis J, Parissis J, Katsanos S, Tsilivarakis D, Hausenloy DJ, Alexopoulos D, Cokkinos DV, Bøtker HE, and Iliodromitis EK
- Subjects
- Adult, Aged, Arteries metabolism, Circulating MicroRNA blood, Endothelial Cells metabolism, Female, Glycocalyx metabolism, Greece, Humans, Inflammation Mediators metabolism, Male, MicroRNAs blood, Middle Aged, Myocardial Reperfusion Injury diagnostic imaging, Myocardial Reperfusion Injury metabolism, Myocardial Reperfusion Injury physiopathology, Oxidative Stress, Prospective Studies, Regional Blood Flow, ST Elevation Myocardial Infarction diagnostic imaging, ST Elevation Myocardial Infarction physiopathology, Time Factors, Treatment Outcome, Vascular Stiffness, Arteries physiopathology, Ischemic Postconditioning adverse effects, Myocardial Reperfusion Injury prevention & control, Percutaneous Coronary Intervention adverse effects, ST Elevation Myocardial Infarction therapy, Upper Extremity blood supply, Ventricular Function, Left, Ventricular Remodeling
- 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 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.
- Published
- 2021
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