Cardioprotective effects of Glucagon-like Peptide 1 (GLP-1) and their mechanisms

Background Glucagon-like Peptide 1 (GLP-1) is a human incretin hormone that has been demonstrated to protect against non-lethal ischaemia reperfusion injury in the left ventricle in humans. It has been suggested from some animal research that this protection may be mediated through the pathway of ischaemic conditioning, of which the opening of the mKATP channel is a key step. Furthermore, it is uncertain whether the protection applies to the right ventricle. Finally, there is limited human evidence of a protective effect against lethal ischaemia reperfusion injury. Methods Two studies use non-lethal ischaemia to test whether GLP-1 protection is maintained despite blockade of the mKATP channel with the sulfonylurea, glibenclamide. A demand ischaemia study uses dobutamine stress echo to compare LV function. The other uses transient coronary balloon occlusion to generate supply ischaemia during GLP-1 infusion, assessed by conductance catheter. A further transient balloon occlusion is also used to assess the effect of supply ischaemia on RV function. Finally, the GOLD PCI study assesses whether GLP-1 protects against periprocedural myocardial infarction when administered during elective PCI in a randomised, placebo controlled double blind trial. Results Glibenclamide did not affect GLP-1 cardioprotection in either supply of demand ischaemia suggesting that GLP-1 protection is not mediated through the mKATP channel. The RV experienced stunning with RCA balloon occlusion but there was little evidence of cumulative ischaemic dysfunction with further occlusions. GOLD PCI is continuing to recruit patients. The nature of the study means results cannot be assessed until recruitment is complete. Conclusions GLP-1 is an agent with potential for clinical use as a cardioprotective therapy. It’s mechanism of action in the heart remains uncertain.

Name dc:type.qualificationname

Doctor of Medicine (MD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2017

Author dc:creator

• Giblett, Joel Peter

Advisors dc:contributor.advisor

• Bennett, Martin
• Dutka, David

• Cardioprotection
• glucagon-like peptide 1
• ischaemia-reperfusion injury
• interventional cardiology

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/8e5dfce2-d1da-4625-8673-5152cf07c68d/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

en

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.8511

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/263201