Chronic erythropoietin treatment decreases post-infarct myocardial damage in rats without venous thrombogenic effect.
OBJECTIVE
Whereas administration of erythropoietin (EPO) acutely after myocardial infarction (MI) reduces infarct size and chronic EPO therapy attenuates post-MI remodeling, the safety of chronic EPO therapy following MI is unknown. Therefore, we examined the thrombogenic effects of a chronic EPO therapy after MI.


METHODS
Rats underwent coronary occlusion followed by reperfusion. They were assigned to one of the following groups: EPO-A, single injection of EPO 5,000 U/kg at the time of reperfusion; EPO-C, injection of EPO 5,000 U/kg at the time of reperfusion followed by 300 U/kg/week; PBS-C, injection of vehicle only. After eight weeks of treatment they were exposed to a validated prethrombotic test based on partial stenosis of the inferior vena cava.


RESULTS
As compared to the rats receiving vehicle only, the rats treated with EPO exhibited a significant reduction in MI size (28.7 +/- 2.1% and 25.8 +/- 1.9 vs. 39.8 +/- 3.0% in EPO-A, EPO-C and PBS-C, respectively; p < 0.05). Whereas the hematocrit was significantly increased in EPO-C (59.7 +/- 2.0% vs. 44.7 +/- 0.9% in EPO-A, p < 0.001), the proportion of rats in which a thrombus occurred was similar in all groups (p = 0.52).


CONCLUSIONS
Chronic EPO therapy added to the single high dose of EPO injected acutely did not induce venous pro-thrombotic effect in rats.
Prunier
F
F
Protection et remodelage du myocarde, UPRES EA 3860, Faculté de Médecine et Centre Hospitalier Universitaire, rue Haute de Reculée, Angers Cedex 1, France. faprunier@chu-angers.fr
Pottier
P
P
Clairand
R
R
Mercier
A
A
Hajjar
R J
RJ
Planchon
B
B
Furber
A
A
D000818:Animals; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D006400:Hematocrit; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020246:Venous Thrombosis / Q000517:prevention & control*; D020257:Ventricular Remodeling / Q000187:drug effects*
D004921:Erythropoietin