Sustained-release erythropoietin ameliorates cardiac function in infarcted rat-heart without inducing polycythemia

Abstract

Background: The usefulness of sustained-release erythropoietin for improving left ventricular (LV) function without polycythemia was evaluated in a rat chronic myocardial infarction model. Methods and Results: Four weeks after left coronary artery ligation, 50 Sprague-Dawley rats were assigned to 5 groups (n=10, each). Control group had a gelatin sheet (20x20mm) containing saline applied to the infarct area, whereas the 4 treatment groups had gelatin sheets incorporating erythropoietin 0.1U, 1U, 10U and 100U, respectively. Endpoint measurements performed at 8 weeks after the coronary ligation revealed that the fractional area change was larger for erythropoietin 1U and 10U than in the other 3 groups. The LV end-systolic elastance and the time constant of isovolumic relaxation were better for erythropoietin 1U and 10U than in the other 3 groups. The density of vessels larger than 50μm in diameter was the highest in the erythropoietin 1U group. The number of red blood cells was significantly increased in groups receiving erythropoietin 10U and 100U. Conclusions: Gelatin hydrogel sheets incorporating 1U erythropoietin improved LV function without inducing polycythemia in a rat chronic myocardial infarction model.