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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on September 8, 2004; DOI: 10.1124/jpet.104.073890

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*GLUCAGON


Received for publication July 22, 2004.
Revised September 7, 2004.
Accepted for publication September 7, 2004.

Glucagon-Like Peptide-1 (GLP-1) Limits Myocardial Stunning Following Brief Coronary Occlusion and Reperfusion in Conscious Canines

Lazaros A. Nikolaidis 1, Aaron Doverspike 1, Teresa Hentosz 1, Lee Zourelias 1, You-Tang Shen 1, Dariush Elahi 2, Richard P. Shannon 1*

1 Cardiovascular Research Institute, Department of Medicine, Allegheny General Hospital, Pittsburgh, P 2 University of Massachusetts School of Medicine, Worcester, MA

* Address correspondence to: E-mail: rshannon{at}wpahs.org

Abstract

We have recently demonstrated the benefits of Glucagon-like peptide-1 (GLP-1) in enhancing regional and global myocardial function following reperfusion in the clinical setting of acute myocardial infarction. We hypothesized that GLP-1 facilitates recovery from myocardial stunning following an ischemic event. To investigate this, we administered GLP-1 (1.5 pmol/kg/min) to 6 dogs undergoing 10 min occlusion of the left circumflex coronary artery, followed by 24-hour reperfusion. We compared the responses of coronary blood flow and regional thickening of the posterior wall with a group of 8 vehicle-treated dogs undergoing the same occlusion-reperfusion protocol. While recovery of coronary blood flow was identical, regional wall motion recovery occurred significantly (*p< 0.05) earlier (92±4% vs 57±5%* at 15 min) and was complete in the GLP-1 treated dogs, while residual contractile dysfunction persisted in the control group (99±4% vs 78±3%* at 24hrs). This phenomenon was independent of changes in systemic hemodynamics or global systolic function. However, isovolumic LV 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 following successful reperfusion


Key words: Coronary artery occlusion, Glucagon-like peptide, Myocardial Ischemia, Myocardial Reperfusion, Myocardial Stunning, Myocardial function


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