Abstract 14545: Glucagon-Like Peptide-1 Receptor Activation With Liraglutide During Acute Myocardial Infarction Improves Myocardial Salvage and Systolic Left Ventricular Function
Introduction: Glucagon-like Peptide-1 (GLP-1) is an intestinal hormone that plays an important role for normal glucose tolerance. Recent studies suggest that GLP-1 has anti-apoptotic and cytoprotective actions. Liraglutide is a GLP-1 receptor (GLP-1r) agonist used for the treatment of Type 2 diabetes that may also confer cardioprotective effects. The objective of our study was to investigate the cardioprotective effects of Liraglutide 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 received either Liraglutide (1.2 mg i.v.; n=7) 10 minutes prior to reperfusion and then twice daily for the next 3 days, or saline for controls (n=7). MI size and LV function were assessed by contrast-enhanced cardiac MRI, one week and one month post-MI induction.
Results: One week after MI induction, Liraglutide significantly reduced infarct size compared to controls (34.4 ± 1.3% vs. 39.6 ± 1.6% of LV, p < 0.05), measured by delayed gadolinium enhancement. Importantly, there was no difference in the area at risk between groups. Further, Liraglutide treatment significantly improved LVEF one week post MI (41.1 ± 1.6% vs. 33.1 ± 0.7%, p < 0.05). Importantly, these cardioprotective effects of Liraglutide were preserved one month post-MI (LVEF 44.7 ± 2.1% vs. 32.9 ± 1.3%, p < 0.05). Also, at one month, the contractile reserve during Dobutamine MRI was significantly greater in Liraglutide pigs compared with controls. In addition, Liraglutide treated pigs demonstrated decreased LV remodeling one month post MI (LV mass 53.8 ± 2.1 g vs. 70.2 ± 2.0 g, p < 0.05, LVESV 53.9 ± 5.0 ml vs. 77.5 ± 6.5 ml, p < 0.05).
Conclusions: Our results demonstrate that GLP-1r activation with Liraglutide prior to reperfusion significantly reduced infarct size. In addition, Liraglutide significantly improved systolic left ventricular function at one week and one month, and Liraglutide mitigated adverse LV remodeling. These results strongly suggest a cardioprotective role for GLP-1 signaling. In conclusion, our observations indicate the therapeutic potential of the GLP-1 system in the setting of acute MI. Further studies in humans are warranted.
- © 2013 by American Heart Association, Inc.