OBJECTIVES: We assessed the effects of erythropoietin (EPO) treatment in a rat 
model of post-myocardial infarction (MI) heart failure.
BACKGROUND: Erythropoietin, traditionally known as a hematopoietic hormone, has 
been linked to neovascularization. Whereas administration of EPO acutely after 
MI reduces infarct size and improves cardiac function, its role in the failing 
heart is unknown.
METHODS: Rats underwent coronary ligation or sham surgery. Rats with MI were 
randomly assigned to: untreated (MI), a single bolus of EPO immediately after MI 
induction (MI-EPO-early), EPO treatment immediately after MI and once every 
three weeks (MI-EPO-early+late), and EPO treatment starting three weeks after 
induction of MI, once every three weeks (MI-EPO-late). After nine weeks, 
hemodynamics, infarct size, myosin heavy chain (MHC) isoforms, myocyte 
hypertrophy, and capillary density were measured.
RESULTS: Erythropoietin treatment started immediately after MI (MI-EPO-early and 
MI-EPO-early+late) resulted in a 23% to 30% reduction in infarct size (p < 0.01) 
and, accordingly, hemodynamic improvement. Erythropoietin treatment, started 
three weeks after MI (MI-EPO-late), did not affect infarct size, but resulted in 
an improved cardiac performance, reflected by a 34% reduction in left 
ventricular end-diastolic pressure (p < 0.01), and 46% decrease in atrial 
natriuretic peptide levels (p < 0.05). The improved cardiac function was 
accompanied by an increased capillary density (p < 0.01), an increased 
capillary-to-myocyte ratio (p < 0.05), and a partial reversal of beta-MHC (p < 
0.05) in all treated groups.
CONCLUSIONS: In addition to its effect on infarct size reduction, EPO treatment 
improves cardiac function in a rat model of post-MI heart failure. This 
observation may be explained by neovascularization, associated with an increased 
alpha-MHC expression.