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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GLP-1 (7-36) amide and Glibenclamide | Experimental | Patients will receive 5mg Glibenclamide orally prior to PCI and infusion of GLP-1 (7-36) amide 1.2 pmol/Kg/min during PCI |
|
| Glibenclamide alone | Experimental | Glibenclamide 5 mg orally prior to PCI |
|
| GLP-1 (7-36) amide | Active Comparator | GLP-1 (7-36) amide |
|
| Saline control | No Intervention | 0.9% saline only (no treatment with GLP-1 (7-36) amide or glibenclamide) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GLP-1 (7-36) amide | Drug | Infusion of GLP-1 (7-36) amide 1.2 pmol/Kg/min |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Measured at the time of procedure |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Measured at the time of the procedure |
| Maximal rate of change with time of left ventricular pressure - dP/dt max (mmHg/s) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen P Hoole, MD | Papworth Hospital NHS Foundation Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Papworth Hospital | Cambridge | Cambridgeshire | CB23 3RE | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27431258 | Derived | 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. |
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| ID | Term |
|---|---|
| D000787 | Angina Pectoris |
| D015428 | Myocardial Reperfusion Injury |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C055453 | glucagon-like peptide 1 (7-36)amide |
| D005905 | Glyburide |
| ID | Term |
|---|---|
| D013453 | Sulfonylurea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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| Glibenclamide | Drug | Oral Glibenclamide 5mg |
|
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. |
| Measured at the time of the procedure |
| Minimum rate of change with time of left ventricular pressure - dP/dt min (mmHg/s) | 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. | Measured at the time of procedure |
| D002637 |
| Chest Pain |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009202 | Cardiomyopathies |
| D015427 | Reperfusion Injury |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013450 |
| Sulfones |
| D013457 | Sulfur Compounds |