Abstract 953: Erythropoietin Administration after Myocardial Infarction in Mice Prevents Late Ischemic Cardiomyopathy
Objective: Recent reports have shown additional effects of Erythropoietin (EPO) beside its classical function in erythropoiesis, like antiapoptotic effects and stem cell mobilization. These effects are known to improve myocardial regeneration after myocardial infarction (MI). We aimed to define survival, functional parameters as well as cell proliferation and stem cell mobilization in a murine model of surgically induced MI after treatment with EPO.
Methods: Human EPO (3000 IE/kg) was injected intraperitoneally immediately after ligation of the left anterior descendens (LAD) as well as on the two consecutive days (1000 IE/kg). 6 days after application different subpopulations of mobilized stem cells were determined by flow cytometry. 30 days after MI pressure volume relationships were investigated in vivo using conductance catheters. Furthermore, histological analysis was performed to determine infarct size at day 6 and at day 30.
Results: FACS analysis 6 days after EPO application demonstrated a significant increase of different CD34+ stem cell populations (CD31+, c-kit+, Sca-1+). EPO treated animals showed a significant improvement of survival post MI (62% vs. 36%). Comparison of pressure-volume loops between EPO treated and non-treated infarcted mice revealed a pronounced difference of cardiac function (EF: 22.9 ± 2.7% vs. 15.0 ± 2.0%). In addition elasticity demonstrated a less degree of infarct remodelling (Elasticity: 21.0 ± 3.4 vs. 8.1 ± 0.9 mmHg/μl). Histological analysis of EPO treated mice revealed a reduced decline of the thickness of the free LV wall at the two time points.
Conclusion: EPO administration after myocardial infarction is associated with a pronounced stem cell mobilization, reduced infarct size, an improved rate of survival as well as remodelling and demonstrated a beneficial role on long term myocardial function up to 4 weeks after MI. Therefore, mobilization of autologous bone marrow derived cells presents a promising non-invasive approach to ameliorate heart failure post MI.