Erythropoietin enhances neovascularization of ischemic myocardium and improves left ventricular dysfunction after myocardial infarction in dogs.
OBJECTIVE
We investigated the effects of erythropoietin (EPO) on neovascularization and cardiac function after myocardial infarction (MI).


BACKGROUND
Erythropoietin exerts antiapoptotic effects and mobilizes endothelial progenitor cells (EPCs).


METHODS
We intravenously administered EPO (1,000 IU/kg) immediately [EPO(0) group], 6 h [EPO(6h) group], or 1 week [EPO(1wk) group] after the permanent ligation of the coronary artery in dogs. Control animals received saline immediately after the ligation.


RESULTS
The infarct size 6 h after MI was significantly smaller in the EPO(0) group than in the control group (61.5 +/- 6.0% vs. 22.9 +/- 2.2%). One week after MI, the circulating CD34-positive mononuclear cell numbers in both the EPO(0) and the EPO(6h) groups were significantly higher than in the control group. In the ischemic region, the capillary density and myocardial blood flow 4 weeks after MI was significantly higher in both the EPO(0) and the EPO(6h) groups than in the control group. Four weeks after MI, left ventricular (LV) ejection fraction in the EPO(6h) (48.6 +/- 1.9%) group was significantly higher than that in either the control (41.9 +/- 0.9%) or the EPO(1wk) (42.6 +/- 1.2%) group but significantly lower than that in the EPO(0) group (56.1 +/- 2.3%). The LV end-diastolic pressure 4 weeks after MI in both the EPO(0) and the EPO(6h) groups was significantly lower than either the control or the EPO(1wk) group. Hematologic parameters did not differ among the groups.


CONCLUSIONS
In addition to its acute infarct size-limiting effect, EPO enhances neovascularization, likely via EPC mobilization, and improves cardiac dysfunction in the chronic phase, although it has time-window limitations.
Hirata
Akio
A
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Minamino
Tetsuo
T
Asanuma
Hiroshi
H
Fujita
Masashi
M
Wakeno
Masakatsu
M
Myoishi
Masafumi
M
Tsukamoto
Osamu
O
Okada
Ken-ichiro
K
Koyama
Hidekazu
H
Komamura
Kazuo
K
Takashima
Seiji
S
Shinozaki
Yoshiro
Y
Mori
Hidezo
H
Shiraga
Masamichi
M
Kitakaze
Masafumi
M
Hori
Masatsugu
M
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002196:Capillaries / Q000033:anatomy & histology; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004921:Erythropoietin / Q000627:therapeutic use*; D006439:Hemodynamics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology*
D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin