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 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.

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

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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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Keywords

  • Ischemia–reperfusion injury
  • Remote conditioning
  • Arterial stiffness
  • Oxidative stress
  • Endothelial glycocalyx
  • Remodelling