Glucagon-like Peptide-1 Derived Cardioprotection Does Not Utilize a KATP-channel Dependent Pathway: Mechanistic Insights from Human Supply and Demand Ischemia Studies

Overview

Journal Cardiovasc Diabetol

Publisher Biomed Central

Specialties Cardiology & Vascular Diseases
Endocrinology

Date 2016 Jul 20

PMID 27431258

Citations 8

Authors

Joel P Giblett

Richard G Axell

Paul A White

Sophie J Clarke

Liam McCormick

Philip A Read

Johannes Reinhold

Adam J Brown

Michael OSullivan

Nick E J West

David P Dutka

Stephen P Hoole

Affiliations

Soon will be listed here.

Abstract

Background: Glucagon-like peptide-1 (7-36) amide (GLP-1) protects against stunning and cumulative left ventricular dysfunction in humans. The mechanism remains uncertain but GLP-1 may act by opening mitochondrial K-ATP channels in a similar fashion to ischemic conditioning. We investigated whether blockade of K-ATP channels with glibenclamide abrogated the protective effect of GLP-1 in humans.

Methods: Thirty-two non-diabetic patients awaiting stenting of the left anterior descending artery (LAD) were allocated into 4 groups (control, glibenclamide, GLP-1, and GLP-1 + glibenclamide). Glibenclamide was given orally prior to the procedure. A left ventricular conductance catheter recorded pressure-volume loops during a 1-min low-pressure balloon occlusion (BO1) of the LAD. GLP-1 or saline was then infused for 30-min followed by a further 1-min balloon occlusion (BO2). In a non-invasive study, 10 non-diabetic patients were randomized to receive two dobutamine stress echocardiograms (DSE) during GLP-1 infusion with or without oral glibenclamide pretreatment.

Results: GLP-1 prevented stunning even with glibenclamide pretreatment; the Δ % dP/dtmax 30-min post-BO1 normalized to baseline after GLP-1: 0.3 ± 6.8 % (p = 0.02) and GLP-1 + glibenclamide: -0.8 ± 9.0 % (p = 0.04) compared to control: -11.5 ± 10.0 %. GLP-1 also reduced cumulative stunning after BO2: -12.8 ± 10.5 % (p = 0.02) as did GLP-1 + glibenclamide: -14.9 ± 9.2 % (p = 0.02) compared to control: -25.7 ± 9.6 %. Glibenclamide alone was no different to control. Glibenclamide pretreatment did not affect global or regional systolic function after GLP-1 at peak DSE stress (EF 74.6 ± 6.4 vs. 74.0 ± 8.0, p = 0.76) or recovery (EF 61.9 ± 5.7 vs. 61.4 ± 5.6, p = 0.74).

Conclusions: Glibenclamide pretreatment does not abrogate the protective effect of GLP-1 in human models of non-lethal myocardial ischemia. Trial registration Clinicaltrials.gov Unique Identifier: NCT02128022.

Citing Articles

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Aetesam-Ur-Rahman M, Giblett J, Khialani B, Kyranis S, Clarke S, Zhao T BMC Cardiovasc Disord. 2021; 21(1):223.

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Cardioprotection for Acute MI in Light of the CONDI2/ERIC-PPCI Trial: New Targets Needed.

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Glucagon-Like Peptide-1-Mediated Cardioprotection Does Not Reduce Right Ventricular Stunning and Cumulative Ischemic Dysfunction After Coronary Balloon Occlusion.

Giblett J, Axell R, White P, Aetesam-Ur-Rahman M, Clarke S, Figg N JACC Basic Transl Sci. 2019; 4(2):222-233.

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Besch G, Perrotti A, Salomon du Mont L, Puyraveau M, Ben-Said X, Baltres M Cardiovasc Diabetol. 2018; 17(1):140.

PMID: 30384842 PMC: 6211400. DOI: 10.1186/s12933-018-0784-y.

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