Exenatide Reduces Infarct Size and Improves Cardiac Function in a Porcine Model of Ischemia and Reperfusion Injury

Objectives This study sought to examine whether exenatide is capable of reducing myocardial infarct size. Background Exenatide is a glucagon-like peptide (GLP)-1 analogue with insulinotropic and insulinomimetic properties. Because insulin and GLP-1 have been described as reducing apoptosis, exenatide might confer cardioprotection after acute myocardial infarction (MI). Methods Pigs were randomized to exenatide or phosphate-buffered saline (PBS) treatment after 75 min of coronary artery ligation and subsequent reperfusion. Infarct size was assessed with Evans Blue (Sigma-Aldrich, St. Louis, Missouri) and triphenyltetrazolium chloride. Cardiac function was measured with epicardial ultrasound and conductance catheter-based pressure-volume loops. Western blotting, histology, and activity assays were performed to determine markers of apoptosis/survival and oxidative stress. Results Exenatide reduced myocardial infarct size (32.7 ± 6.4% vs. 53.6 ± 3.9%; p = 0.031) and prevented deterioration of systolic and diastolic cardiac function (systolic wall thickening: 47.3 ± 6.3% vs. 8.1 ± 1.9%, p Conclusions These data identify exenatide as a potentially effective compound to reduce infarct size in adjunction to reperfusion therapy in patients with acute MI.