The effects of remote ischaemic preconditioning on coronary artery function in patients with stable coronary artery disease

D Corcoran, R Young, P Cialdella, P McCartney, A Bajrangee, B Hennigan, D Collison, D Carrick, A Shaukat, R Good, S Watkins, M McEntegart, J Watt, P Welsh, N Sattar, A McConnachie, K G Oldroyd, C Berry, D Corcoran, R Young, P Cialdella, P McCartney, A Bajrangee, B Hennigan, D Collison, D Carrick, A Shaukat, R Good, S Watkins, M McEntegart, J Watt, P Welsh, N Sattar, A McConnachie, K G Oldroyd, C Berry

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.

Keywords: Cardioprotection; Coronary artery disease; Endothelial function; Myocardial infarction; Remote ischaemic preconditioning.

Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Illustration of the RIC-COR study protocol. RIPC = remote ischaemic preconditioning.
Fig. 2
Fig. 2
CONSORT (Consolidated Standards of Reporting Trials) flow diagram. RIPC = remote ischaemic preconditioning.

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