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

Thomas J. Povsic, 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 Lakatta, Robert A. Harrington, Sunil V. Rao

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)375-383
Number of pages9
JournalJournal of Thrombosis and Thrombolysis
Volume36
Issue number4
DOIs
StatePublished - Nov 2013
Externally publishedYes

Fingerprint

Erythropoietin
Therapeutics
Cell Count
ST Elevation Myocardial Infarction
Endothelial Progenitor Cells
Cryopreservation
Percutaneous Coronary Intervention
Reperfusion Injury
Multicenter Studies
Placebos

Keywords

  • Cryopreservation
  • Endothelial progenitor cells
  • Erythropoietin
  • Myocardial infarction

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction : The REVEAL EPC substudy. / Povsic, Thomas J.; Najjar, Samer S.; Prather, Kristi; Zhou, Jiying; Adams, Stacie D.; Zavodni, Katherine L.; Kelly, Francine; Melton, Laura G.; Hasselblad, Vic; Heitner, John F.; Raman, Subha V.; Barsness, Gregory W.; Patel, Manesh R.; Kim, Raymond J.; Lakatta, Edward; Harrington, Robert A.; Rao, Sunil V.

In: Journal of Thrombosis and Thrombolysis, Vol. 36, No. 4, 11.2013, p. 375-383.

Research output: Contribution to journalArticle

Povsic, TJ, Najjar, SS, Prather, K, Zhou, J, Adams, SD, Zavodni, KL, Kelly, F, Melton, LG, Hasselblad, V, Heitner, JF, Raman, SV, Barsness, GW, Patel, MR, Kim, RJ, Lakatta, E, Harrington, RA & Rao, SV 2013, 'EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction: The REVEAL EPC substudy', Journal of Thrombosis and Thrombolysis, vol. 36, no. 4, pp. 375-383. https://doi.org/10.1007/s11239-013-0944-6
Povsic, Thomas J. ; Najjar, Samer S. ; Prather, Kristi ; Zhou, Jiying ; Adams, Stacie D. ; Zavodni, Katherine L. ; Kelly, Francine ; Melton, Laura G. ; Hasselblad, Vic ; Heitner, John F. ; Raman, Subha V. ; Barsness, Gregory W. ; Patel, Manesh R. ; Kim, Raymond J. ; Lakatta, Edward ; Harrington, Robert A. ; Rao, Sunil V. / EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction : The REVEAL EPC substudy. In: Journal of Thrombosis and Thrombolysis. 2013 ; Vol. 36, No. 4. pp. 375-383.
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AU - Povsic, Thomas J.

AU - Najjar, Samer S.

AU - Prather, Kristi

AU - Zhou, Jiying

AU - Adams, Stacie D.

AU - Zavodni, Katherine L.

AU - Kelly, Francine

AU - Melton, Laura G.

AU - Hasselblad, Vic

AU - Heitner, John F.

AU - Raman, Subha V.

AU - Barsness, Gregory W.

AU - Patel, Manesh R.

AU - Kim, Raymond J.

AU - Lakatta, Edward

AU - Harrington, Robert A.

AU - Rao, Sunil V.

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N2 - 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.

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