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Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines

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AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.104.073890

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  1. PHS HHS [R01-A6 023125] Funding Source: Medline

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We have recently demonstrated the benefits of glucagon-like peptide-1 (GLP-1) in enhancing regional and global myocardial function after reperfusion in the clinical setting of acute myocardial infarction. We hypothesized that GLP-1 facilitates recovery from myocardial stunning after an ischemic event. To investigate this, we administered GLP-1 (1.5 pmol/kg/min) to six dogs undergoing 10-min occlusion of the left circumflex coronary artery, followed by 24-h reperfusion. We compared the responses of coronary blood flow and regional thickening of the posterior wall with a group of eight vehicle-treated dogs undergoing the same occlusion-reperfusion protocol. Although recovery of coronary blood flow was identical, regional wall motion recovery occurred significantly (*p < 0.05) earlier ( 92 +/- 4 versus 57 +/- 5%* at 15 min) and was complete in the GLP-1-treated dogs, whereas residual contractile dysfunction persisted in the control group ( 99 +/- 4 versus 78 +/- 3%* at 24 h). This phenomenon was independent of changes in systemic hemodynamics or global systolic function. However, isovolumic left ventricular relaxation improved significantly in GLP-1-treated dogs. GLP-1 caused an insulinotropic effect, but no hypoglycemia. We conclude that GLP-1 enhances recovery from ischemic myocardial stunning after successful reperfusion.

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