Abstract 12379: Glucagon-Like Peptide-1 Receptor Activation During Myocardial Ischemia Causes Short- and Long-Term Improvements in Myocardial Infarction Size and Left Ventricular Function
Introduction: Glucagon-like Peptide-1 (GLP-1) is essential for normal glucose tolerance and evidence suggests that it has anti-apoptotic and cytoprotective actions. Exenatide is a GLP-1 receptor (GLP-1r) agonist used for the treatment of Type 2 diabetes, and may also confer clinical benefits through cardiac GLP-1r activation. The objective of our study was to investigate the cardioprotective effects of GLP-1r activation in the setting of acute myocardial ischemia (MI) and reperfusion.
Methods: Acute MI was induced in Yorkshire pigs by balloon occlusion of the proximal LAD for 60 minutes, followed by reperfusion. Animals were randomly assigned to receive either Exenatide (10 μ g i.v.; n=5) 10 minutes prior to reperfusion and then twice daily for the next 3 days, or saline for controls (n=4). The extent of the MI and myocardial function were assessed by contrast-enhanced cardiac MRI, one week and one month post-MI induction.
Results: One week after MI induction, Exenatide lead to a 10% reduction in infarct size compared to controls (34.5 ± 1.1% vs. 37.8 ± 1.0% of LV, p < 0.05), measured by delayed gadolinium enhancement. Further, Exenatide improved LV stroke volume (35.4±0.9ml vs. 28.2 ± 1.0 ml, p < 0.01) without differences in the LV end-diastolic volume between groups. The ejection fraction was higher in Exenatide-treated animals (39.5 ± 0.9% vs. 33.5 ± 0.5%, p < 0.01). The echocardiographic findings were concordant with the MRI measurements, demonstrating an improved 3D-LVEF (39.5 ± 2.4% vs. 33.5 ± 1.1%, p < 0.01) at one week in the Exenatide group. Importantly, these cardioprotective effects of Exenatide were preserved at one month post-MI. In addition, Exenatide decreased LV remodeling at one month (LV mass 59.3 ± 5.4 g vs. 66.2 ± 3.7 g, p < 0.05, LV mass/LVEDV 0.53 ± 0.07 vs. 0.68 ± 0.1, p = 0.06).
Conclusions: Our results indicate that GLP-1r activation by Exenatide initiated prior to reperfusion significantly reduces infarct size. In addition, Exenatide significantly improved systolic left ventricular function at one week and one month. These results strongly suggest a cardioprotective role for GLP-1 signaling. In conclusion, our observations underscore the therapeutic potential of the GLP-1 system in patients with MI, and further studies in humans are warranted.
- © 2011 by American Heart Association, Inc.