Myocardial reperfusion injury management: erythropoietin compared with postconditioning.

Abstract

Ischemic postconditioning (IPost) and erythropoietin (EPO) have been shown to attenuate myocardial reperfusion injury using similar signaling pathways. The aim of this study was to examine whether EPO is as effective as IPost in decreasing postischemic myocardial injury in both Langendorff-isolated-heart and in vivo ischemia-reperfusion rat models. Rat hearts were subjected to 25 min ischemia, followed by 30 min or 2 h of reperfusion in the isolated-heart study. Rats underwent 45 min ischemia, followed by 24 h of reperfusion in the in vivo study. In both studies, the control group (n=12; ischemia-reperfusion only) was compared with IPost (n=16; 3 cycles of 10 s reperfusion/10 s ischemia) and EPO (n=12; 1,000 IU/kg) at the onset of reperfusion. The following resulted. First, in the isolated hearts, IPost or EPO significantly improved postischemic recovery of left ventricular developed pressure. EPO induced better left ventricular developed pressure than IPost at 30 min of reperfusion (73.18+/-10.23 vs. 48.11+/-7.92 mmHg, P<0.05). After 2 h of reperfusion, the infarct size was significantly lower in EPO-treated hearts compared with IPost and control hearts (14.36+/-0.60%, 19.11+/-0.84%, and 36.21+/-4.20% of the left ventricle, respectively; P<0.05). GSK-3beta phosphorylation, at 30 min of reperfusion, was significantly higher with EPO compared with IPost hearts. Phosphatidylinositol 3-kinase and ERK1/2 inhibitors abolished both EPO- and IPost-mediated cardioprotection. Second, in vivo, IPost and EPO induced an infarct size reduction compared with control (40.5+/-3.6% and 28.9+/-3.1%, respectively, vs. 53.7+/-4.3% of the area at risk; P<0.05). Again, EPO decreased significantly more infarct size and transmurality than IPost (P<0.05). In conclusion, with the use of our protocols, EPO showed better protective effects than IPost against reperfusion injury through higher phosphorylation of GSK-3beta.

• Authors: Sophie Tamareille, Nehmat Ghaboura, Frederic Treguer, Dalia Khachman, Anne Croué, Daniel Henrion, Alain Furber, Fabrice Prunier
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 297 Issue 6 Pg. H2035-43 (Dec 2009) ISSN: 1522-1539 [Electronic] United States
• PMID: 19617412 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors
• Erythropoietin
• Darbepoetin alfa
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Glycogen Synthase Kinase 3

Topics

• Animals
• Cardiotonic Agents (therapeutic use)
• Coronary Circulation (drug effects)
• Darbepoetin alfa
• Disease Models, Animal
• Erythropoietin (analogs & derivatives, pharmacology)
• Female
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Heart Rate (drug effects)
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors, metabolism)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, metabolism)
• Myocardial Infarction (enzymology, pathology, physiopathology, prevention & control)
• Myocardial Reperfusion Injury (enzymology, pathology, physiopathology, prevention & control)
• Myocardium (enzymology, pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Wistar
• Time Factors
• Ventricular Function, Left (drug effects)
• Ventricular Pressure (drug effects)