Erythropoietin induces neovascularization and improves cardiac function in rats with heart failure after myocardial infarction.
OBJECTIVE
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.
van der Meer
Peter
P
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands. p.van.der.meer@thorax.azg.nl
Lipsic
Erik
E
Henning
Robert H
RH
Boddeus
Kristien
K
van der Velden
Jolanda
J
Voors
Adriaan A
AA
van Veldhuisen
Dirk J
DJ
van Gilst
Wiek H
WH
Schoemaker
Regien G
RG
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects*; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects*; D000068256:Darbepoetin alfa; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D018995:Myosin Heavy Chains / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004921:Erythropoietin; D000068256:Darbepoetin alfa; D009320:Atrial Natriuretic Factor; D018995:Myosin Heavy Chains