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New Therapy for Treatment of Endothelial Dysfunction – Simple & Noninvasive

Int J Cardiol. 2018 Feb 1;252:24-30. doi: 10.1016/j.ijcard.2017.10.082. The effects of remote ischaemic preconditioning on coronary artery function in patients with stable coronary artery disease. Corcoran D1, Young R2, Cialdella P3, McCartney P1, Bajrangee A3, Hennigan B1, Collison D4, Carrick D3, Shaukat A3, Good R3, Watkins S3, McEntegart M3, Watt J3, Welsh P4, Sattar N4, McConnachie A2, Oldroyd KG3, Berry C5. Author information 1British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Scotland, UK; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, Scotland, UK.2Robertson Centre for Biostatistics, University of Glasgow, Scotland, UK.3West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, Scotland, UK.4British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Scotland, UK.5British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Scotland, UK; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, Scotland, UK. Electronic address: colin.berry@glasgow.ac.uk. Abstract BACKGROUND: Remote ischaemic preconditioning (RIPC) is a cardioprotective intervention invoking intermittent periods of ischaemia in a tissue or organ remote from the heart. The mechanisms of this effect are incompletely understood. We hypothesised that RIPC might enhance coronary vasodilatation by an endothelium-dependent mechanism. METHODS: We performed a prospective, randomised, sham-controlled, blinded clinical trial. Patients with stable coronary artery disease (CAD) undergoing elective invasive management were prospectively enrolled, and randomised to RIPC or sham (1:1) prior to angiography. Endothelial-dependent vasodilator function was assessed in a non-target coronary artery with intracoronary infusion of incremental acetylcholine doses (10-6, 10-5, 10-4mol/l). Venous blood was sampled pre- and post-RIPC or sham, and analysed for circulating markers of endothelial function. Coronary luminal diameter was assessed by quantitative coronary angiography. The primary outcome was the between-group difference in the mean percentage change in coronary luminal diameter following the maximal acetylcholine dose (Clinicaltrials.gov identifier: NCT02666235). RESULTS: 75 patients were enrolled. Following angiography, 60 patients (mean±SD age 57.5±8.5years; 80% male) were eligible and completed the protocol (n=30 RIPC, n=30 sham). The mean percentage change in coronary luminal diameter was -13.3±22.3% and -2.0±17.2% in the sham and RIPC groups respectively (difference 11.32%, 95%CI: 1.2- 21.4, p=0.032). This remained significant when age and sex were included as covariates (difference 11.01%, 95%CI: 1.01- 21.0, p=0.035). There were no between-group differences in endothelial-independent vasodilation, ECG parameters or circulating markers of endothelial function. CONCLUSIONS: RIPC attenuates the extent of vasoconstriction induced by intracoronary acetylcholine infusion. This endothelium-dependent mechanism may contribute to the cardioprotective effects of RIPC. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved. KEYWORDS: Cardioprotection; Coronary artery disease; Endothelial function; Myocardial infarction; Remote ischaemic preconditioning Related Symposium Endothelial Function Scientific Update Sponsored by Endothelix Inc.

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