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Journal of Thrombosis and Thrombolysis

, Volume 36, Issue 4, pp 375–383 | Cite as

EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction: the REVEAL EPC substudy

  • Thomas J. PovsicEmail author
  • Samer S. Najjar
  • Kristi Prather
  • Jiying Zhou
  • Stacie D. Adams
  • Katherine L. Zavodni
  • Francine Kelly
  • Laura G. Melton
  • Vic Hasselblad
  • John F. Heitner
  • Subha V. Raman
  • Gregory W. Barsness
  • Manesh R. Patel
  • Raymond J. Kim
  • Edward G. Lakatta
  • Robert A. Harrington
  • Sunil V. Rao
Article

Abstract

Erythropoietin (EPO) was hypothesized to mitigate reperfusion injury, in part via mobilization of endothelial progenitor cells (EPCs). The REVEAL trial found no reduction in infarct size with a single dose of EPO (60,000 U) in patients with ST-segment elevation myocardial infarction. In a substudy, we aimed to determine the feasibility of cryopreserving and centrally analyzing EPC levels to assess the relationship between EPC numbers, EPO administration, and infarct size. As a prespecified substudy, mononuclear cells were locally cryopreserved before as well as 24 and 48–72 h after primary percutaneous coronary intervention. EPC samples were collected in 163 of 222 enrolled patients. At least one sample was obtained from 125 patients, and all three time points were available in 83 patients. There were no significant differences in the absolute EPC numbers over time or between EPO- and placebo-treated patients; however, there was a trend toward a greater increase in EPC levels from 24 to 48–72 h postintervention in patients receiving ≥30,000 U of EPO (P = 0.099 for CD133+ cells, 0.049 for CD34+ cells, 0.099 for ALDHbr cells). EPC numbers at baseline were inversely related to infarct size (P = 0.03 for CD133+ cells, 0.006 for CD34+ cells). Local whole cell cryopreservation and central EPC analysis in the context of a multicenter randomized trial is feasible but challenging. High-dose (≥30,000 U) EPO may mobilize EPCs at 48–72 h, and baseline EPC levels may be inversely associated with infarct size.

Keywords

Erythropoietin Endothelial progenitor cells Myocardial infarction Cryopreservation 

Notes

Acknowledgments

The authors would like to thank Peter Hoffmann for thoughtful editorial and logistical support. The REVEAL study was supported by Intramural Research Program contract HHS-N-260-2005-00010-C from the National Institute on Aging, Bethesda, MD, USA. The first author was the recipient of a Duke Pepper Older Americans Independence Center Research Career Development Program in Aging Research Award (5P30AG028716), Durham, NC, USA.

Conflict of interest

Dr. Povsic has received grants from Baxter International, Regado Biosciences, and Theragen. Dr. Najjar has received research funding from HeartWare. Dr. Hasselblad has received salary support via Grants from Eli Lilly and Medicure Inc. administered through Duke University. Dr. Heitner reported that New York Methodist Hospital received compensation for his work as a principal investigator for a study; also, he has received compensation for his expert testimony in an individual malpractice case, Grant support from the Empire Clinical Research Investigator Program, and compensation for serving on a steering committee for a trial. Dr. Raman has received Grant support from the National Institutes of Health and from Siemens Corporation. Dr. Barsness has been a consultant for Hoffmann-La Roche, Inc. and Baxter Healthcare Corporation, and has received research funding from Gilead Sciences, Inc. Dr. Patel has served as a board member for Genzyme’s advisory board and Bayer Healthcare, and as a consultant for Ikaria. Dr. Kim was an inventor on a U.S. patent for Delayed Enhancement MRI, which is owned by Northwestern University. Dr. Harrington’s complete listing of disclosure information is available at https://www.dcri.org/about-us/conflict-of-interest/COI-Harrington_2012.pdf. Dr. Rao received research funding from Novartis, Cordis Corporation, and Ikaria; and was a consultant for Sanofi-Aventis, Bristol-Meyers Squibb, Astra- Zeneca, Daiichi Sankyo-Lilly, and Terumo USA. The other authors report no disclosures.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Thomas J. Povsic
    • 1
    • 2
    • 3
    Email author
  • Samer S. Najjar
    • 4
    • 5
  • Kristi Prather
    • 1
  • Jiying Zhou
    • 2
  • Stacie D. Adams
    • 2
  • Katherine L. Zavodni
    • 2
  • Francine Kelly
    • 2
  • Laura G. Melton
    • 1
  • Vic Hasselblad
    • 1
  • John F. Heitner
    • 6
  • Subha V. Raman
    • 7
  • Gregory W. Barsness
    • 8
  • Manesh R. Patel
    • 1
    • 2
  • Raymond J. Kim
    • 2
  • Edward G. Lakatta
    • 5
  • Robert A. Harrington
    • 1
    • 2
  • Sunil V. Rao
    • 1
    • 2
    • 3
  1. 1.Duke Clinical Research Institute, Duke University Medical CenterDurhamUSA
  2. 2.Division of Cardiology, Department of MedicineDuke University School of MedicineDurhamUSA
  3. 3.Durham Veterans Affairs Medical CenterDurhamUSA
  4. 4.MedStar Health Research InstituteWashingtonUSA
  5. 5.Intramural Research Program, National Institute on Aging, National Institutes of HealthBaltimoreUSA
  6. 6.New York Methodist HospitalBrooklynUSA
  7. 7.Division of Cardiovascular MedicineOhio State UniversityColumbusUSA
  8. 8.Mayo ClinicRochesterUSA

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