Abstract 548: Synergistic Protective Effect of Glucagon-Like Peptide-1 and α-Melanocyte Stimulating Hormone Fused to Transferrin on Myocardial Reperfusion Injury
Background: Glucagon-like peptide 1 (GLP-1) and α-Melanocyte Stimulating Hormone (α-MSH) have been reported to have antiapoptotic properties which may make these drugs useful adjuncts to reperfusion therapy for myocardial infarction. However, the very short half-life (minutes) of both drugs limits their therapeutic applicability. Fusion of each drug to transferrin (GLP-1-Tf and MSH-Tf) extends its functional half-life to days.
Method: New Zealand rabbits (n= 52) underwent left thoracotomy, thirty minutes of myocardial ischemia and three hours of reperfusion. Area at risk (RA) and infarct size as a percentage of the RA (IA/RA) were determined using a double staining technique. Left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) were assessed by echocardiography. There were four experimental groups: Control (n=24) saline injection, GLP-1-Tf Group (n=10) single dose GLP-1-Tf (10mg/kg), MSH-Tf Group (n=10) single dose MSH-Tf (10mg/kg), Mixed-Tf Group (n=8) GLP-1-MSH-Tf (10mg/kg). Each treatment group was given the drug intravenously at the onset of reperfusion.
Results: RA in all four groups was similar. All three treatment groups experienced similar reductions in IA/RA compared to control animals; however, echocardiography demonstrated significantly reduced LVEDV and LVESV in Mixed-Tf group at three hours of reperfusion, whereas single drug did not.
Conclusion: Both GLP-1-Tf and MSH-Tf limit myocardial reperfusion injury. The combination of both drugs does not further reduce infarct size but does improve early post infarct remodeling.