Cardioprotective Effects of GLP-1 and Their Mechanisms

Investigation Into Cardioprotective Effect of Glucagon-like Peptide-1 and it's Mechanism of Action During Myocardial Ischaemia

Ischaemic heart disease is the most common cause of death in the UK. Glucagon-like peptide-1 (GLP-1) has been demonstrated to protect the heart when it is deprived of blood supply (ischaemia). The mechanism for this protection is not clear. Similar protection occurs with ischaemic conditioning of the heart, which is dependent on potassium channel opening. The investigators intend to establish whether GLP-1 mediated protection shares a similar mechanistic pathway. In order to do this the investigators will measures pressure--volume loops generated in the main pumping chamber of the heart at the time of a percutaneous coronary intervention (stenting). Patients will be allocated to GLP-1 alone, GLP-1 with glibenclamide (a potassium channel blocking medication approved for human use), saline control or glibenclamide alone. The investigators hypothesis is that the effect of GLP-1 will be abrogated by use of glibenclamide.

Glucagon-Like Peptide 1, Angina Pectoris, Percutaneous Coronary Intervention, Ischemic Preconditioning, Myocardial Reperfusion Injury

Patients will receive 5mg Glibenclamide orally prior to PCI and infusion of GLP-1 (7-36) amide 1.2 pmol/Kg/min during PCI

The isovolumetric relaxation constant, Tau, a measure of left ventricular diastolic function, will be measured during the second balloon occlusion of the coronary artery. This will be measured on pressure-volume loop using a conductance catheter.

Ejection fraction, a measure of left ventricular systolic function, will be measured during the second balloon occlusion of the coronary artery. This will be measured on pressure-volume loop using a conductance catheter.

dP/dt max, a measure of left ventricular systolic function, will be measured during the second balloon occlusion of the coronary artery. This will be measured on pressure-volume loop using a conductance catheter.

dP/dt min, a measure of left ventricular diastolic function, will be measured during the second balloon occlusion of the coronary artery. This will be measured on pressure-volume loop using a conductance catheter.

Inclusion Criteria: Age over 18 Able to give informed consent Elective percutaneous intervention for a single vessel coronary stenosis Normal left ventricular function Exclusion Criteria: Severe Co-morbidity Type 2 Diabetes Mellitus Nicorandil, Sulphonylureas, DPP4 inhibitors, GLP-1 agonists or Insulin use Women of child bearing age Myocardial infarction in previous three months Previous coronary artery bypass grafts

Giblett JP, Axell RG, White PA, Clarke SJ, McCormick L, Read PA, Reinhold J, Brown AJ, O'Sullivan M, West NE, Dutka DP, Hoole SP. Glucagon-like peptide-1 derived cardioprotection does not utilize a KATP-channel dependent pathway: mechanistic insights from human supply and demand ischemia studies. Cardiovasc Diabetol. 2016 Jul 19;15:99. doi: 10.1186/s12933-016-0416-3.