Cardioprotective Effects of GLP-1 and Their Mechanisms

Papworth Hospital NHS Foundation Trust32 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Angina Pectoris

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change in Isovlumetric Relaxation Constant - Tau (ms)

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.

Time frame: Measured at the time of procedure

Secondary Outcomes

Left Ventricular Ejection Fraction (%)

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.

Time frame: Measured at the time of the procedure

Maximal rate of change with time of left ventricular pressure - dP/dt max (mmHg/s)

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.