Abstract 15794: Glucagon-Like Peptide-1 Receptor Activation Improves Systolic LV Function and LV Mechanics in a Porcine Model of Ischemia and Reperfusion
Introduction: Glucagon-like Peptide-1 (GLP-1) is an intestinal hormone secreted after nutrient ingestion that plays a key role in the control of glucose metabolism. Further, GLP-1 has anti-apoptotic and cytoprotective effects in the myocardium. Exenatide is a GLP-1 mimetic used to treat Type 2 diabetes. Our group has demonstrated that Exenatide-mediated GLP-1 receptor (GLP-1r) activation reduces acute myocardial injury and reduces infarct size during ischemia and reperfusion. We sought to determine if GLP-1r activation in the peri-infarct period also improves myocardial function and LV mechanics in the remodeling phase after myocardial infarction (MI).
Methods: Acute MI was induced in Yorkshire pigs by balloon occlusion of the proximal LAD for 60 minutes, followed by reperfusion. Animals randomly received either Exenatide (10 μ g i.v.; n=6) 10 minutes prior to reperfusion and then twice daily for the next 3 days, or saline for controls (n=6). LV systolic function and LV mechanics were assessed with 3D echocardiography one month post MI for measurement of LVEF and 3D echo strain analysis.
Results: One month after MI induction, GLP-1r activation with Exenatide during the peri-infarct period led to a significant improvement in LV systolic function compared with controls (3D LVEF 40.4 ± 1.8% vs. 32.5 ± 3.8%, p < 0.05). GLP-1r activation also resulted in improved 3D Global Longitudinal Strain (-16.4 ± 3.1% vs. -12.1 ± 1.3%, p < 0.05), 3D Circumferential Strain (-17.8 ± 3.4% vs. -11.4 ± 4.0%, p < 0.05), and 3D Radial Strain (58.1 ± 17.1% vs. 32.4 ± 9.7%, p < 0.05).
Conclusions: Our results indicate that GLP-1r activation by Exenatide in the peri-infarct period mitigates the damaging effects of myocardial ischemia, thereby resulting in improved LV systolic function and LV mechanics one month after ischemia reperfusion injury. These data support a cardioprotective role for GLP-1 signaling that extends beyond the acute phase of myocardial ischemia. Our findings suggest that activating the GLP-1 system in patients with MI has the therapeutic potential to reduce the development of ischemic cardiomyopathy.
- © 2012 by American Heart Association, Inc.