Therapeutic effectiveness of a single vs multiple doses of erythropoietin after experimental myocardial infarction in rats

Chanil Moon, Melissa Krawczyk, Edward Lakatta, Mark I. Talan

Research output: Contribution to journalArticle

Abstract

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. Materials and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)245-251
Number of pages7
JournalCardiovascular Drugs and Therapy
Volume20
Issue number4
DOIs
StatePublished - Aug 2006
Externally publishedYes

Fingerprint

Erythropoietin
Myocardial Infarction
Injections
Hematocrit
Ventricular Remodeling
Therapeutics
Stroke Volume
Ligation
Sprague Dawley Rats
Echocardiography
Coronary Vessels
Erythrocytes

Keywords

  • Cardiac remodeling
  • Erythropoietin
  • Myocardial infarction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

Therapeutic effectiveness of a single vs multiple doses of erythropoietin after experimental myocardial infarction in rats. / Moon, Chanil; Krawczyk, Melissa; Lakatta, Edward; Talan, Mark I.

In: Cardiovascular Drugs and Therapy, Vol. 20, No. 4, 08.2006, p. 245-251.

Research output: Contribution to journalArticle

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title = "Therapeutic effectiveness of a single vs multiple doses of erythropoietin after experimental myocardial infarction in rats",
abstract = "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. Materials and 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. Conclusion: 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.",
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AB - 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. Materials and 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. Conclusion: 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.

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