title: Administration of erythropoietin fails to improve long-term healing or cardiac function after myocardial infarction in the rat.
abstract: Erythropoietin (epo), initially recognized and used clinically to increase erythropoiesis, has been shown to have beneficial effects on various other tissues in the setting of hypoxia and ischemia. Epo has been shown to reduce apoptosis after myocardial infarction, but few studies have evaluated the long-term effects of epo treatment on left ventricular (LV) remodeling, cardiac function, and blood flow after healing of a permanent coronary artery occlusion. The aim of this study was to assess the effects of epo treatment on the healed heart 6 weeks after myocardial infarction. Anesthetized rats underwent coronary artery occlusion and were treated with erythropoietin (5000 units/kg/day, n=21) or saline (n=20) the day before surgery, the day of, then for 5 days. At 6 weeks LV ventriculography to assess LV volumes and ejection fractions and histologic assessment of infarct size and LV cavity and wall dimensions were performed. Overall epo had no effect on LV remodeling or cardiac function. There were no significant differences in infarct morphology, infarct size (44+/-3% of the LV circumference versus 39+/-3%), LV cavity area, scar thickness, LV systolic volume, or ejection fraction (44+/-3% versus 39+/-3%) between the epo and saline groups, respectively. However, for any given size of myocardial infarct, LV ejection fraction was significantly higher in erythropoietin hearts and LV systolic volumes lower. Thus, in our model, treatment with epo had no long-term beneficial effect on LV remodeling after myocardial infarction but may have exerted some positive effect on LV function.
authors.affiliation: The Heart Institute of Good Samaritan Hospital and the Keck School of Medicine, Division of Cardiovascular Medicine, University of Southern California, Los Angeles, California 90017, USA. sharon.hale@netscape.com
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hale
authors.forename: Casilde
authors.initials: C
authors.lastname: Sesti
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kloner
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D013997:Time Factors; D017211:Treatment Failure; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa