Effects of Liraglutide on Cardiac Function and Myocardial Infarct Size in the Setting of Obesity

Abstract

Glucagon like peptide‐1 (GLP‐1) based therapies have been shown to improve cardiac function and protect against myocardial ischemic injury in non‐obese animals. However, whether these therapies confer protection against ischemic damage in the setting of obesity has not been established. Obese Ossabaw swine were subjected to a gradually developing coronary occlusion by placement of an ameroid occluder on the left anterior descending coronary artery. Animals then received daily subcutaneous injections of saline or the stable GLP‐1 analogue, liraglutide (0.005‐0.015 mg/kg/day) for 30 days. Following this treatment period, animals were anesthetized and an open chest procedure was performed to assess cardiac and systemic responses to administration of the sympathomimetic compound, dobutamine (0.3‐30 μg/kg/min). Liraglutide treatment had no effect on baseline hemodynamic variables, including mean pressure (P = 0.32), stroke volume (P = 0.80), heart rate (P = 0.26), or ejection fraction (P = 0.80). Dobutamine administration dose‐dependently increased heart rate, systolic ejection pressure, dP/dtmax, stroke work, and decreased contraction time, left ventricular end diastolic volume, and stroke volume. Dobutamine‐induced changes were unaffected by liraglutide administration. Excised hearts were sliced into 1cm thick sections and stained with tetrazolium to quantify the area of myocardial infarction. Overall, total myocardial infarct size was not significantly different in between groups (P = 0.41). These findings indicate that liraglutide does not significantly affect cardiac function or myocardial infarct size in the setting of obesity.