Prolonged therapy with erythropoietin is safe and prevents deterioration of left ventricular systolic function in a porcine model of myocardial infarction

Abstract

Background: Erythropoietin (EPO) has generated interest as a novel therapy after myocardial infarction (MI), but the safety and efficacy of prolonged therapy have not been studied in a large animal model of reperfused MI.

Methods and results: MI was induced in pigs by a 90-minute balloon occlusion of the left anterior descending coronary artery. Sixteen animals were randomized to either EPO or saline (control group). Inflammatory markers, bone marrow cell mobilization, and left ventricular function (by both echocardiography and pressure-volume measurements) were assessed at baseline, 1 and 6 weeks post-MI. EPO therapy was associated with a significant increase in hemoglobin and mononuclear counts. D-dimer and C-reactive protein levels did not differ between groups. At week 6, EPO therapy prevented further deterioration of left ventricular ejection fraction (39 +/- 2% vs. 33 +/- 1%, P < .01) and improved wall motion score index (P < .02). Histopathology revealed increased areas of viable myocardium, vascular density, and capillary-to-myocyte ratio in the EPO therapy compared with the control (all P < .05).

Conclusion: Prolonged EPO therapy after MI in a large animal model is safe and leads to an increase in viable myocardium, increased vascular density, and prevents further deterioration of left ventricular function. These results support future clinical studies in post-MI patients.