Myocardial infarction (MI) causes loss of myocytes and may lead to loss of ventricular function, morbidity and mortality. The most effective therapy is early reperfusion of the ischemic myocardium by percutaneous coronary intervention (PCI). Reperfusion limits myocardial ischaemic necrosis, but also induces inflammation, oxidative stress and calcium overload: a process referred to as reperfusion injury leading to necrosis and apotosis. Glucagon Like Peptide-1 (GLP-1) is an incretin hormone that has shown to activate anti-apoptotic enzymes, reducing reperfusion injury. GLP-1 agonists have been demonstrated to be cardioprotective in several animal studies and in a single small non-randomized clinical study. In this pilot study we will assess the safety and efficacy of GLP-1 receptor agonist Exenatide infusion compared to placebo in patients with an acute myocardial infarction undergoing primary PCI.

A total of 40 patients will be included in this single centre prospective randomised placebo controlled two-arm pilot study. Patients who are to undergo a primary PCI for a first acute ST elevation myocardial infarction are randomly assigned to placebo or Exenatide 5ug bolus in 30 minutes, followed by a continuous Exenatide infusion of 20ug/ 24 hours for 72 hours. Blood samples are obtained for assessment of enzymatic infarct size and Exenatide levels. Side effects of Exenatide are stringently monitored. Cardiac function will be measured using Cardiac Magnetic Resonance Imaging (CMRI) and 3D echocardiography at 1 week and 4 months post MI. Infarct size will be assessed by means of the final infarct size at 4 months post MI as a percentage of the area at risk at 1 week post MI. Furthermore we will compare the RNA profile of both groups.

Inclusion Criteria:

• >18 and < 80 years of age
• First myocardial infarction
• ST elevation of more than one mm in at least 2 separate leads on the electrocardiogram (ECG)
• Delay between onset of sustained chestpain and PCI < 6 hours.

Exclusion Criteria:

• Cardiac rhythm is other than normal sinus rhythm.
• Patient in Killip class 3 or 4 of heart failure
• Cardiogenic shock defined as sustained systolic blood pressure ≤ 80mmHg despite fluid hydration.
• Post cardiac resuscitation
• Need for intra aortic balloon counterpulsation therapy
• The patient is unable to hold his/her breath for up to 20 seconds due to age or concomitant illness
• No former PCI performed
• No recanalisation achieved of the occluded coronary artery
• Culprit not in segment 1,2,3,6,7,11,12,13 of the coronary artery
• No definite culprit
• More than one occluded vessel, or a more than 70% stenosis by visual assessment in a non-culprit vessel.
• TIMI 3 flow in culprit lesion at presentation
• Decreased renal function eGFR < 30ml/min
• Any contraindication for MRI ie: implanted electronic devices such as pacemakers, internal defibrillators, neurostimulators, implanted drug infusion devices, cochlear implants, cerebrovascular clips, claustrophobia. previous vascular surgery: aneurysm clip, carotid artery vascular clamp, aortic clips, venous umbrella spinal/intra-ventricular shunts
• Metal fragments in eye, head, ear, skin or shoulder.
• Swann-Ganz catheter.
• Known pre-existing left ventricular dysfunction measured by any technique (ejection fraction < 45% prior to current admission for myocardial infarction)
• Prior myocardial infarction
• Prior coronary artery bypass grafting
• Moderate to severe cardiac valve disease
• Stroke or transient ischemic attack within the previous 24 hours
• Serious known concomitant disease with a life expectancy of less than one year
• Follow up impossible
• Previous participation in a trial within the previous 30 days
• Known type I Diabetes Mellitus
• Known type II Diabetes Mellitus
• Pregnancy and/or lactation