In-vivo monitoring of erythropoietin treatment after myocardial infarction in mice with [⁶⁸Ga]Annexin A5 and [¹⁸F]FDG PET

J Nucl Cardiol. 2014 Dec;21(6):1191-9. doi: 10.1007/s12350-014-9987-0. Epub 2014 Sep 5.

Abstract

Background: Several studies substantiate the cardioprotective effects of erythropoietin (EPO). Our goal was to quantify the effects of EPO treatment on the early expression of the apoptosis marker phosphatidylserine as well as on the left ventricular volumes and function by means of small animal PET.

Methods and results: Myocardial infarction (MI) was induced in C57BL/6 mice. Animals were assigned to saline or EPO groups and underwent Annexin PET (day 2) and gated FDG PET (days 6 and 30). Annexin uptake was significantly higher in the infarction than in remote myocardium, with no differences between treatment groups. Infarct size showed a slight decrease in the EPO group and a slight increase in the controls, which did not reach statistical significance. Follow-up analyses revealed a significant increase of end-diastolic and end-systolic volumes in the EPO group, in which a stable left ventricular ejection fraction (LVEF) was maintained.

Conclusion: We find that deleterious effects of EPO can outweigh cardioprotective effects. The present EPO treatment did not significantly reduce apoptosis after MI, but seemingly provoked significant myocardial dilation while maintaining a stable LVEF. Molecular mechanisms of EPO treatment may need further elucidation to optimize therapy regimens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5* / pharmacokinetics
  • Cardiotonic Agents / therapeutic use
  • Drug Monitoring / methods*
  • Erythropoietin / therapeutic use*
  • Fluorodeoxyglucose F18* / pharmacokinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / diagnostic imaging*
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Positron-Emission Tomography
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Treatment Outcome

Substances

  • Annexin A5
  • Cardiotonic Agents
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Erythropoietin