The Long Acting GLP‐1 Receptor Agonist, Liraglutide, Augments Myocardial Contractile Responses and Cardiac Efficiency Under Sympathetic Stimulation in Obesity and Myocardial Infarction
Authors: Goodwill Adam Glenn , Sassoon Daniel J , Noblet Jillian N , Conteh Abass M , Mather Kieren J , Tune Johnathan D 
Published: November 2023

This study tested the hypothesis that GLP‐1 based therapies improve cardiac contractile function at rest and in response to beta‐adrenergic stimulation in an obese swine model of ischemic heart disease. Ossabaw swine were fed a high calorie, obesogenic diet for 6 months. Following this period, swine were subjected to a gradually developing coronary occlusion by placement of an ameroid occluder on the left anterior descending (LAD) coronary artery. Animals then received daily subcutaneous injections of saline or the stable GLP‐1 analogue liraglutide (0.005–0.015mg/kg/day) for 30 days. Following this treatment, animals were anesthetized and an open chest procedure was performed to assess cardiac performance in response to a sympathomimetic challenge (dobutamine 0.3–10 μg/kg/min) using a left ventricular pressure/volume admittance catheter.Liraglutide administration did not influence the magnitude of myocardial infarction in response to LAD occlusion (saline 16 ± 2% vs liraglutide 14 ± 4%; P = 0.8). Baseline cardiac output and ejection fraction were not different between treatment groups at rest or in response to dobutamine. Thirty days of treatment with liraglutide did not modify the effects of dobutamine to increase pulse pressure, heart rate, dP/dtmax, or contractility index. Indices of diastolic relaxation during dobutamine stimulation were augmented in liraglutide treated animals (dP/dt min P < 0.001, Tau ½ P <0.001, Tau 1/e P < 0.001). Dobutamine reduced left ventricular end diastolic volume, end systolic volume, and stroke volume similarly in saline and liraglutide treated animals. However, the slope of the end systolic pressure volume relationship (ESPVR; load‐independent contractility) was significantly increased by dobutamine following liraglutide (4.2 ± 1.1 vs 21.8 ± 8.4 mmHg/ml; P <0.001) but not saline (8.7 ± 5.9 vs 14.8 ± 3.5 mmHg/ml; P = 0.63). Dobutamine increased the volume axis intercept (Vo) of ESPVR in both groups, but this effect was ~50% smaller in animals treated with liraglutide at the lower dobutamine infusion rates (0.3 and 1 μg/kg/min; P < 0.05). While cardiac efficiency (stroke work/pressure volume area) was similar between treatment groups at baseline (70 ± 7% vs 69 ± 3; P = 0.92), liraglutide significantly enhanced cardiac efficiency under the highest dobutamine infusion rate (10 μg/kg/min; P = 0.017).Taken together, these data suggest that GLP‐1 agonism augments diastolic relaxation, contractility, and cardiac efficiency under sympathetic stimulation in the setting of obesity and regional myocardial infarction.Support or Funding InformationThis study was supported by R01HL11760 (J. Tune and K. Mather, PI). Dr. Goodwill was supported by American Heart Association 13POST1681001813 (A. Goodwill, PI). Ms. Noblet and Mr. Sassoon were supported by TL1 TR000162 (A. Shekhar, PI) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award.