Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

• Published in: International journal of cardiology Vol. 274; pp. 40 - 44
• Main Authors: Verouhis, Dinos, Saleh, Nawzad, Settergren, Magnus, Sörensson, Peder, Gourine, Andrey, Pernow, John
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2019
• Subjects: Adult; Brachial Artery - physiopathology; Cardioprotection; Endothelial function; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Flow-mediated dilatation; Glucagon-like peptide-1; Glucagon-Like Peptide-1 Receptor - antagonists & inhibitors; Glucagon-Like Peptide-1 Receptor - metabolism; Healthy Volunteers; Humans; Injections, Intravenous; Ischemia-reperfusion; Ischemic Preconditioning, Myocardial - methods; Male; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Peptide Fragments - administration & dosage; Remote ischemic conditioning; Vasodilation - physiology; Ischemia-reperfusion; Remote ischemic conditioning; Glucagon-like peptide-1; Cardioprotection; Endothelial function; Flow-mediated dilatation
• ISSN: 0167-5273; 1874-1754; 1874-1754
• DOI: 10.1016/j.ijcard.2018.09.061

Remote ischemic conditioning (RIC), i.e. short cycles of ischemia and reperfusion in remote tissue, is a novel approach to protect against myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction. The nature of the factors transmitting the protective effect of RIC remains unknown, and both neuronal and hormonal mechanisms appear to be involved. A recent study indicated involvement of glucagon-like peptide-1 (GLP-1) regulated by the vagal nerve in RIC in rats. In the present study we aimed to investigate whether the protective effect of RIC is mediated by a GLP-1 receptor-dependent mechanism in humans. Endothelial function was determined from flow-mediated dilatation (FMD) of the brachial artery before and after 20 min of forearm ischemia and 20 min of reperfusion in twelve healthy subjects on three occasions: (A) ischemia-reperfusion without intervention, (B) ischemia-reperfusion + RIC and (C) iv administration of the GLP-1 receptor antagonist exendin(9-39) + ischemia-reperfusion + RIC. Ischemia-reperfusion reduced FMD from 4.7 ± 0.8% at baseline to 1.5 ± 0.4% (p < 0.01). RIC protected from the impairment in FMD induced by ischemia-reperfusion (4.6 ± 1.1% at baseline vs. 5.0 ± 1.1% following ischemia-reperfusion). Exendin(9-39) abolished the protection induced by RIC (FMD 4.9 ± 0.9% at baseline vs. 1.4 ± 1.3% following ischemia-reperfusion; p < 0.01) but did not affect basal FMD. Plasma GLP-1 levels did not change significantly between examinations. The present study is the first to suggest that RIC protects against endothelial ischemia-reperfusion injury via a GLP-1 receptor-mediated mechanism in humans. •Remote ischemic conditioning attenuates endothelial ischemia reperfusion injury.•The protection is abolished by the GLP-1 receptor antagonist exendin(9-39).•Remote ischemic conditioning acts via a GLP-1 receptor dependent mechanism.