title: Low-dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit.
abstract: BACKGROUND
  Erythropoietin (EPO) may improve cardiac function and induce neovascularisation in experimental models of chronic heart failure (CHF). However, the increased haematocrit associated with EPO treatment might exert concomitant deleterious effects.
  
  
  OBJECTIVE
  To investigate the haematocrit independent effects of EPO on cardiac function.
  
  
  RESULTS
  Rats underwent permanent coronary artery ligation to induce myocardial infarction (MI) or sham surgery. Three weeks after MI, rats were randomly allocated to treatment with vehicle (MI) or the long-acting EPO analogue darbepoetin alfa administered in a high (40 microg/kg/3 weeks, MI-EPO-high) or a low-dose (0.4 microg/kg/3 weeks, MI-EPO-low). After 9 weeks, haemodynamic parameters, myocardial histology and Myosin Heavy Chain (MHC) isoforms were determined. High-dose EPO resulted in a significant increase in haematocrit (p<0.01) while low-dose EPO had no effect on haematocrit levels. EPO significantly improved cardiac function in both EPO groups, reflected by increased left ventricular (LV)-developed pressure and improved contractility (dP/dt(max)) and relaxation (dP/dt(min)) indices of the LV at 9-weeks (all p<0.05 compared to MI). The improved cardiac function was associated with increased capillary growth (38% in MI-EPO-high (p<0.01) and 27% in MI-EPO-low (p<0.05)) and an attenuated switch to slow beta-MHC isoforms in both EPO groups.
  
  
  CONCLUSIONS
  EPO improves cardiac function and induces neovascularisation at a dose that does not increase haematocrit, thereby circumventing the possible deleterious effects of increased erythropoiesis.
authors: Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors: Erik
authors: E
authors: Lipsic
authors: B Daan
authors: BD
authors: Westenbrink
authors: Peter
authors: P
authors: van der Meer
authors: Pim
authors: P
authors: van der Harst
authors: Adriaan A
authors: AA
authors: Voors
authors: Dirk J
authors: DJ
authors: van Veldhuisen
authors: Regien G
authors: RG
authors: Schoemaker
authors: Wiek H
authors: WH
authors: van Gilst
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002196:Capillaries; D003331:Coronary Vessels; D000068256:Darbepoetin alfa; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006397:Hematinics / Q000627:therapeutic use*; D006400:Hematocrit; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics; D018919:Neovascularization, Physiologic; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D006397:Hematinics; D004921:Erythropoietin; D000068256:Darbepoetin alfa