title: Evaluation of the effect of one large dose of erythropoietin against cardiac and cerebral ischemic injury occurring during cardiac surgery with cardiopulmonary bypass: a randomized double-blind placebo-controlled pilot study.
abstract: Cardiac surgery and cardiopulmonary bypass (CPB) induce ischemia-reperfusion and subsequent cellular injury with inflammatory reaction. Clinical and experimental studies suggest that recombinant human erythropoietin (EPO) independently of its erythropoietic effect may be used as a cytoprotective agent against ischemic injury. We tested the hypothesis that one large dose of EPO administered shortly before CPB prevents the elevation of cardiac and cerebral ischemic blood markers as well as the systemic inflammatory response induced by cardiac surgery with CBP through this randomized double-blind placebo-controlled pilot trial. Fifty patients scheduled for coronary artery bypass graft (CABG) surgery with CPB were randomly allocated to EPO or control groups. EPO (800 IU/kg intravenously) or placebo (saline) was administered before CPB. The primary end point was to study the effect of EPO administration on several blood markers of myocardial and cerebral ischemia in relation to CABG with CPB. In both groups, surgery increased plasma concentrations of cardiac (troponin T, NT-proBNP, and creatine kinase MB) and cerebral (S100β protein) markers ischemic as well as the pro-inflammatory marker interleukin-6. Compared with the placebo, EPO administration before CPB did not prevent an increase of all these markers following CPB. In conclusion, one large dose of EPO, given shortly before CPB, did not protect against cardiac and cerebral ischemia and inflammatory response occurring during CABG surgery with CPB. Although the long-term clinical implications remain unknown, the findings do not support use of EPO at this dose as a cytoprotective agent in patients undergoing cardiac surgery.
authors.affiliation: UJF, Laboratoire HP2, Grenoble F-38000, France. marie.joyeux@ujf-grenoble.fr
authors.forename: Marie
authors.initials: M
authors.lastname: Joyeux-Faure
authors.forename: Michel
authors.initials: M
authors.lastname: Durand
authors.forename: Damien
authors.initials: D
authors.lastname: Bedague
authors.forename: Daniel
authors.initials: D
authors.lastname: Protar
authors.forename: Pascal
authors.initials: P
authors.lastname: Incagnoli
authors.forename: Adeline
authors.initials: A
authors.lastname: Paris
authors.forename: Christophe
authors.initials: C
authors.lastname: Ribuot
authors.forename: Patrick
authors.initials: P
authors.lastname: Levy
authors.forename: Olivier
authors.initials: O
authors.lastname: Chavanon
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood; D019610:Cytoprotection / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D009414:Nerve Growth Factors / Q000097:blood; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D020107:Troponin T; C103998:epoetin beta; D004921:Erythropoietin