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 & Results: We block-randomised 270 patients within 48h 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 minutes 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). and reduced MDA was observed after both protocols. Increased miR-144 was related with 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.

Remote Ischemic Perconditioning Ameliorates Myocardial Ischemia and Reperfusion-Induced Coronary Endothelial Dysfunction and Aortic Stiffness in Rats

“…38 The potential benefit of vascular conditioning on aortic stiffness in STEMI patients has been demonstrated previously, however it was measured at baseline (within 48 h after PCI) and 40 min after onset of RIC. 27 In our study, we also could demonstrate the favorable effect of RIPerc on aortic stiffness which was associated with the attenuation of post-infarct LV remodeling (4 weeks after reperfusion). Nevertheless, we cannot exclude that other cardioprotective mechanisms triggered by RIC also alleviates adverse remodeling.…”

“…14 Notably, either one or two cycles of bilateral brachial cuff inflation (vascular conditioning) within 48 h post-PCI in STEMI-patients resulted in a facilitating reverse LV remodeling in association with a decline in carotid-femoral pulse wave velocity as a surrogate marker of vascular stiffness. 27 In our study, we also assessed the impact of MIR on peripheral vascular endothelial function and stiffness as well as long-term vascular protective effects. Accordingly, our study clearly demonstrates that AMI (4 weeks) initiates endothelial dysfunction in aorta as described previously.…”

Current Knowledge of MicroRNAs (miRNAs) in Acute Coronary Syndrome (ACS): ST-Elevation Myocardial Infarction (STEMI)

“…This current clinical trial (NCT03984123), which evaluates patients within the 48 h of STEMI post-PCI, noted that compared with baseline there were increased levels of miR-150,-21,-208 (p < 0.05) and reduced malondialdehyde after one or two cycles of bilateral brachial cuff inflation. Additionally, increased concentrations of miR-144 were related to the carotid-femoral pulse-wave velocity reduction (r = 0.763, p < 0.001) after the first cycle inflation [117].…”

Therapeutic Potential of Remote Ischemic Conditioning in Vascular Cognitive Impairment

“…Thus, nitrite is considered as a “storage” pool of NO and a potential endocrine mediator in the plasma. Several clinical and preclinical studies have consistently reported that the concentration of plasma nitrite is upregulated after RIC treatment ( Farah et al, 2018 ; Ikonomidis et al, 2021 ). The augmentation of nitrite was dependent on reactive hyperemia during the reperfusion phase of RIC, which leads to an upregulation of eNOS synthesis and NO release in the ECs ( Dezfulian et al, 2017 ).…”