Abstract 10325: Epicardial Erythropoietin Patch Improves Cardiac Functions and Induces Stem Cell Associated Regeneration After Myocardial Infarction
High-dose intramyocardial Erythropoietin (EPO) therapy protects the myocardium from ischemic injury and promotes beneficial remodelling. We investigated the therapeutic efficacy of EPO at a moderate dose level and compared local and systemic delivery routes in a rat myocardial infarction (MI) model. Following MI, EPO (300 U/kg) was delivered immediately by intraperitoneal (EPO-S, n=25) injection, intramyocardial (EPO-L, n=23) injection or epicardially as an EPO-plus-fibrin patch (EPO-X, n=26). Groups were compared to each other and MI control groups with saline injections (MIC, n=25) or saline-plus-fibrin patch application (MIC-X, n=29). Heart functions were examined under baseline and Dobutamine-induced stress conditions using conductance catheter method 6 weeks after MI. Moreover, blood and myocardium were analysed including candidate genes and proteins at early (24 hours) and late (6 weeks) stages after MI. Results illustrated superior cardiac functions and healing in EPO-X compared with all groups at 6 weeks after MI. Pressure-volume loops in EPO-X demonstrated 38% improved contractility (dpdtmax), 47% better elasticity (dpdtmin) and 15% enhanced ejection fraction compared with MIC-X. Furthermore, dpdtmax was 33% and 22% higher and dpdtmin was 32% and 23% greater in EPO-X compared with EPO-S and EPO-L, respectively. Infarction size, wall thinning, fibrosis and cardiomyocyte hypertrophy in EPO-X were reduced by 34%, 53%, 48% and 22% compared mit MIC-X, respectively. Histological improvements in EPO-L and EPO-S were only moderate. Early real-time PCR analyses in EPO-X revealed exclusively elevated gene levels of intracardiac stem cell homing factors (SDF-1, CXCR-4, CD34), tissue-transformation factors (TGF-beta, MMP-2), anti-apoptotic Bcl-2 and cell cycle progression factor Cdc2. Blood analyses suggested, healing effects in EPO-X might have been hematopoiesis independent. In conclusion, immediate epicardial EPO-plus-fibrin patch better than systemic or local protein delivery restored cardiac performance after MI and early induced key molecules in myocardial regeneration. Therapeutic efficacy might be local-dose dependent.
- © 2013 by American Heart Association, Inc.