Erythropoietin derivate improves left ventricular systolic performance and attenuates left ventricular remodeling in rats with myocardial infarct-induced heart failure.
BACKGROUND
It has been reported that erythropoietin (EPO) attenuates ischemia-induced damage in a variety of tissues. It is unknown whether EPO alters the left ventricular (LV) remodeling process after ischemic insult. Accordingly, we tested the potential benefits of carbamylated EPO (CEPO) on LV remodeling in rats with myocardial infarction (MI).


METHODS
MI was induced by coronary artery ligation in adult male Sprague-Dawley rats. One hour after surgery, rats were randomly assigned to 1 of 2 groups: MI plus placebo injections (placebo, n = 21) and MI plus CEPO injection (CEPO, n = 22). CEPO (10 μg/kg) or placebo was given via tail vein in a blinded fashion daily for the first 3 days, followed by twice a week subcutaneous injection for 6 weeks. Sham surgery was performed in another group of rats (n = 18) without coronary artery ligation. Cardiac function was assessed by echocardiography, hemodynamic, and in vivo and ex vivo LV pressure-volume relationship measurements 6 weeks after MI.


RESULTS
In comparison to placebo-treated rats, CEPO significantly improved LV geometry (LV end systolic dimension: 8.6 ± 0.8 vs. 9.6 ± 1.0 mm; LV end systolic volume: 404 ± 83 vs. 516 ± 122 μL, both P < 0.05). CEPO therapy also reduced the decline of systolic function (fractional shortening: -3.7% ± 1.7% vs. -10.9% ± 2.3%; Emax 0.46 ± 0.20 vs. 0.25 ± 0.08 mm Hg/s, both P < 0.05). Passive diastolic properties of the LV were minimally improved by leftward shift in the ex vivo end diastolic pressure-volume relationship.


CONCLUSIONS
CEPO administration 1 hour after acute MI improves systolic performance and may attenuate the LV remodeling process. Further studies to determine the mechanism of CEPO responsible for its beneficial effects and optimize dosing and timing regimens are warranted.
Xu
Kai
K
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
George
Isaac
I
Klotz
Stefan
S
Hay
Ilan
I
Xydas
Steve
S
Zhang
Geping
G
Cerami
Anthony
A
Wang
Jie
J
D000818:Animals; D004334:Drug Administration Schedule; D004452:Echocardiography; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
C488171:carbamylated erythropoietin; D004921:Erythropoietin