Abstract
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.
Footnotes
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The study was supported in part by National Institutes of Health Grant R01-A6 023125 and American Heart Association Grant (PA-DE affiliate) 0020248U.
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doi:10.1124/jpet.104.073890.
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ABBREVIATIONS: NEFA, nonessential fatty acid(s); GIK, glucose-insulin-potassium; GLP-1, glucagon-like peptide-1; LV, left ventricular; LCX, left circumflex; CBF, coronary blood flow; WTh, wall thickening; LVEDD, left ventricular end-diastole; FS, fractional shortening; dL/dt, diastolic myocardial segment length change; CAO, coronary artery occlusion; CAR, coronary artery reperfusion; C, control.
- Received July 22, 2004.
- Accepted September 7, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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