Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines.
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.
Nikolaidis
Lazaros A
LA
Cardiovascular Research Institute, Department of Medicine, Allegheny General Hospital, 320 East North Ave., Pittsburgh, PA 15212, USA.
Doverspike
Aaron
A
Hentosz
Teresa
T
Zourelias
Lee
L
Shen
You-Tang
YT
Elahi
Dariush
D
Shannon
Richard P
RP
D000818:Animals; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004285:Dogs; D005934:Glucagon / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1; D017202:Myocardial Ischemia / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D017682:Myocardial Stunning / Q000517:prevention & control*; D010446:Peptide Fragments / Q000627:therapeutic use*; D011498:Protein Precursors / Q000627:therapeutic use*
D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon