Lack of cardioprotection from subcutaneously and preischemic administered liraglutide in a closed chest porcine ischemia reperfusion model.
BACKGROUND
Glucagon-like peptide 1 (GLP1) analogues are promising new treatment options for patients with type 2 diabetes, but may have both potentially beneficial and harmful cardiovascular effects. This may also be the case for the analogues of GLP1 for clinical use. The present study examined the effect of treatment with liraglutide, a long-acting GLP1 analogue, on myocardial ischemia and reperfusion in a porcine model.


METHODS
Danish Landrace Pigs (70-80 kg) were randomly assigned to liraglutide (10 mug/kg) or control treatment given daily for three days before ischemia-reperfusion. Ischemia was induced by balloon occlusion of the left anterior descending artery for 40 minutes followed by 2.5 hours of reperfusion. The primary outcome parameter was infarct size in relation to the ischemic region at risk. Secondary endpoints were the hemodynamic parameters mean pulmonary pressure, cardiac output, pulmonary capillary wedge pressure as measured by a Swan-Ganz catheter as well as arterial pressure and heart rate.


RESULTS
The infarct size in relation to ischemic risk region in the control versus the liraglutide group did not differ significantly: 0.46 +/- 0.14 and 0.54 +/- 0.12) (mean and standard deviation (SD), p = 0.21). Heart rate was significantly higher in the liraglutide group during the experiment, while the other hemodynamic parameters did not differ significantly.


CONCLUSIONS
Liraglutide has a neutral effect on myocardial infarct size in a porcine ischemia-reperfusion model.
Kristensen
Jens
J
Department of Cardiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark. jenskristensen@dadlnet.dk
Mortensen
Ulrik M
UM
Schmidt
Morten
M
Nielsen
Peter Haubjerg
PH
Nielsen
Torsten Toftegaard
TT
Maeng
Michael
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002407:Catheterization, Swan-Ganz; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007279:Injections, Subcutaneous; D000069450:Liraglutide; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013552:Swine
D002317:Cardiovascular Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1