Abstract
BackgroundRemote 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. MethodsWe 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). Results75 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. ConclusionsRIPC attenuates the extent of vasoconstriction induced by intracoronary acetylcholine infusion. This endothelium-dependent mechanism may contribute to the cardioprotective effects of RIPC.
Highlights
Ischaemic conditioning describes the beneficial effects of repeated cycles of ischaemia and reperfusion resulting in cardioprotection against ischaemia-reperfusion injury [1,2,3,4,5,6]
Remote ischaemic preconditioning (RIPC) is associated with a reduction in infarct size in patients following an acute myocardial infarction (MI) and after elective percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) [8,16,17]
We have shown that RIPC performed immediately prior to invasive management results in a lower reduction in mean percentage coronary artery luminal diameter, consistent with enhanced coronary endothelial function
Summary
Ischaemic conditioning describes the beneficial effects of repeated cycles of ischaemia and reperfusion resulting in cardioprotection against ischaemia-reperfusion injury [1,2,3,4,5,6]. 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. 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. 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). This endothelium-dependent mechanism may contribute to the cardioprotective effects of RIPC
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