Single Dose GLP-1-Tf Ameliorates Myocardial Ischemia/Reperfusion Injury

Background. Glucagon-like peptide-1 (GLP-1) has insulinomimetic, insulinotropic, and antiapoptotic properties that may make it a useful adjunct to reperfusion therapy for myocardial infarction (MI); however, GLP-1 has a short plasma half-life. Fusion of GLP-1 to human transferrin (GLP-1-Tf) significantly prolongs drug half-life. Materials and Methods. We tested the ability of single dose GLP-1-Tf to limit myocardial ischemia (30min)/ reperfusion (180 min) injury in rabbits. Nineteen animals were untreated controls. The pre-ischemic group (n = 10) was given 10mg/kg of GLP-1-Tf 12 h before ischemia. Immediately after reperfusion, the post-ischemic group (n = 10) received GLP-1-Tf (10 mg/kg) and the Tf group (n = 4) received transferrin alone. Results. Infarct size as a percentage of the area at risk was 59.1% +/- 1.3%, 45.7% +/- 1.9%, 44.1% +/- 3.3%, 59.7% +/- 2.0% in the control group, pre-ischemic group, post-ischemic group, and Tf group, respectively (P < 0.05 for both GLP-1-Tf treatments group versus control). GLP-1-Tf reduced the apoptotic index from 4.67% +/- 0.40% in the control group to 3.15% +/- 0.46% in the pre-ischemic group and to 2.66% +/- 0.40% in the post-ischemic group (P < 0.05 for both GLP-1-Tf treatments versus control). The size of the wall motion abnormality and ejection fraction was significantly improved in the post-ischemic group relative to the control group. Serum GLP-1 levels were 239.8 +/- 25.7 mu g/mL in the post-ischemic group, 27.9 +/- 5.8 mu g/mL in the pre-ischemic group, and undetectable in the control group. Conclusion. GLP-1-Tf limits myocardial reperfusion injury whether given prior to the onset of ischemia or given at reperfusion. GLP-1-Tf may also limit myocardial stunning at high serum levels of the drug. (C) 2011 Elsevier Inc. All rights reserved.