Therapeutic effectiveness of a single vs multiple doses of erythropoietin after experimental myocardial infarction in rats.
BACKGROUND
Systemic application of recombinant human erythropoietin (rhEPO) greatly limits cardiac tissue damage and attenuates left ventricular (LV) remodeling after experimentally induced myocardial infarction (MI). However, multiple injections of rhEPO stimulate red blood cell production and elevate the hematocrit (Htc), which might negatively affect the outcome of acute MI. We compared the outcome of experimental MI in rats treated with a single or multiple doses of rhEPO.


METHODS
Sprague-Dawley male rats were subjected to a permanent ligation of the left descending coronary artery (CL) or sham operation. Immediately after CL animals received either a single i.v. injection of 3,000 IU/kg of rhEPO, or a single injection plus additional injections of the same dose of rhEPO repeated daily for six more days. Echocardiography and blood collection for measurement of Htc were performed prior to, and at 2 and 4 weeks after CL; MI size was measured histologically 4 weeks after CL.


RESULTS
A single injection of rhEPO elevated Htc by 11% (p < 0.05) 1 week after CL, but after multiple rhEPO injections Htc increased by 40%. In untreated rats a 140 and 340% expansion in end-diastolic and end-systolic LV volumes, respectively, and 55% decline in ejection fraction (EF) occurred during the 4 week period following CL. A single rhEPO dose attenuated the LV remodeling and EF reduction by 50%. Repeated rhEPO injections did not elicit any additional benefits in respect to LV remodeling. Moreover, at the end of 4 weeks, MI size was significantly reduced (by 40%) by a single injection, while after repeated rhEPO injections the reduction of MI size was not statistically significant.


CONCLUSIONS
The results of this study indicate that multiple dosing of rhEPO after induced myocardial infarction in rats has no added therapeutic benefits over those achieved by a single dose.
Moon
Chanil
C
Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Krawczyk
Melissa
M
Lakatta
Edward G
EG
Talan
Mark I
MI
D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004452:Echocardiography; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000473:pathology; D006400:Hematocrit; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D020257:Ventricular Remodeling / Q000187:drug effects
D002316:Cardiotonic Agents; D011994:Recombinant Proteins; D004921:Erythropoietin