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

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Basic Research in Cardiology Aims and scope Submit manuscript

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.

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Availability of data and materials

The datasets generated during and/or analysed during the current study are not publicly available due to confidentiality reasons but are available from the corresponding author on reasonable request.

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Funding

This work has been supported by the EU-CARDIOPROTECTION COST (European Cooperation in Science and Technology-Action) (CA16225) and Hellenic Society of Cardiology.

Author information

Author notes

  1. Ignatios Ikonomidis and Dimitrios Vlastos have contributed equally to this work.

Authors and Affiliations

  1. 2nd Department of Cardiology, Medical School, Attikon Hospital, National and Kapodistrian University of Athens, Rimini 1, Haidari, 12462, Athens, Greece

    Ignatios Ikonomidis, Dimitrios Vlastos, Maria Varoudi, George Makavos, John Lekakis, John Parissis, Spiridon Katsanos, Damianos Tsilivarakis, Dimitrios Alexopoulos & Efstathios K. Iliodromitis

  2. Department of Cardiac Surgery, Royal Brompton Hospital, London, UK

    Dimitrios Vlastos

  3. Laboratory of Pharmacology, School of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece

    Ioanna Andreadou & Panagiotis Efentakis

  4. Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Maria Gazouli

  5. Biomedical Research Foundation, Academy of Athens, Athens, Greece

    Alkistis Kapelouzou & Dennis V. Cokkinos

  6. National Heart Centre, National Heart Research Institute Singapore, Singapore, Singapore

    Derek J. Hausenloy

  7. Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore

    Derek J. Hausenloy

  8. The Hatter Cardiovascular Institute, University College London, London, UK

    Derek J. Hausenloy

  9. The National Institute of Health Research University College London Hospitals Biomedical Research Centre, Research and Development, London, UK

    Derek J. Hausenloy

  10. Centro de Biotecnologia-FEMSA, Tecnologico de Monterrey, Monterrey, Mexico

    Derek J. Hausenloy

  11. Department of Cardiology, Aarhus University Hospital Skejby, Aarhus N, Denmark

    Hans-Eric Bøtker

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  1. Ignatios Ikonomidis
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Contributions

II: analysis and interpretation of data, critical content revision, and final version approval; DV: analysis and interpretation of data, drafting and critical content revision, and final version approval; IA: acquisition of biochemical data, critical content revision, final version approval; MG: acquisition of biochemical data; PE: acquisition of biochemical data; MV: acquisition of vascular function data; GM: acquisition of echocardiography data; AK: acquisition of biochemical data; JL: critical content revision; JP: critical content revision; SK: acquisition of echocardiography data; DT: acquisition of echocardiography data; DJH: critical content revision; DA: critical content revision; DVC: critical content revision; H-EB: critical content revision; EKI: study design, interpretation of data, critical content revision, and final version approval.

Corresponding authors

Correspondence to Ignatios Ikonomidis or Ioanna Andreadou.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The study was approved by the University General Hospital “Attikon” Institutional Review Board, conforms to the principles outlined in the Declaration of Helsinki, and is registered at the US National Institutes of Health (ClinicalTrials.gov: #NCT03984123). In addition, all participants gave their written informed consent.

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Ikonomidis, I., Vlastos, D., Andreadou, I. et al. Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study. Basic Res Cardiol 116, 9 (2021). https://doi.org/10.1007/s00395-021-00851-1

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  • DOI: https://doi.org/10.1007/s00395-021-00851-1

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