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


Journal

International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291

Informations de publication

Date de publication:
01 Jan 2019
Historique:
received: 08 05 2018
revised: 03 09 2018
accepted: 17 09 2018
pubmed: 1 10 2018
medline: 23 7 2019
entrez: 1 10 2018
Statut: ppublish

Résumé

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.

Sections du résumé

BACKGROUND BACKGROUND
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.
METHODS METHODS
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.
RESULTS RESULTS
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.
CONCLUSION CONCLUSIONS
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.

Identifiants

pubmed: 30268384
pii: S0167-5273(18)32752-9
doi: 10.1016/j.ijcard.2018.09.061
pii:
doi:

Substances chimiques

Glucagon-Like Peptide-1 Receptor 0
Peptide Fragments 0
exendin (9-39) 5313W10MYT

Types de publication

Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

40-44

Informations de copyright

Copyright © 2018 Elsevier B.V. All rights reserved.

Auteurs

Dinos Verouhis (D)

Department of Medicine, Unit of Cardiology, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: dinos.verouhis@sll.se.

Nawzad Saleh (N)

Department of Medicine, Unit of Cardiology, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

Magnus Settergren (M)

Department of Medicine, Unit of Cardiology, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

Peder Sörensson (P)

Department of Medicine, Unit of Cardiology, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

Andrey Gourine (A)

Department of Medicine, Unit of Cardiology, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

John Pernow (J)

Department of Medicine, Unit of Cardiology, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

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Classifications MeSH