Preliminary Administration of EPO and Markers of Cardiac Ischemia Induced by CPB (EPOetCEC)

• Area under curve and maximal plasmatic level of protein S-100 after cardiopulmonary bypass [ Time Frame: at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), puis 6 h, 12 h, 24 h et 48h after the end of the cardiopulmonary bypass ] [ Designated as safety issue: Yes ]
• Blood level of erythropoietin [ Time Frame: at injection and 6 hours after the end of cardiopulmonary bypass ] [ Designated as safety issue: No ]

• Area under curve and maximal plasmatic level of protein S-100 after cardiopulmonary bypass
• Blood level of erythropoietin at the injection and 6 hours after the end of the caridopulmonary bypass.

The main objective is to observe the effects of erythropoietin administration on different blood markers of ischaemic cardiac lesions induced by cardiopulmonary bypass.

A new property of erythropoietin (EPO), independent of its hematopoietic role, has recently been discovered. Indeed, it has been reported that this hormone, following binding to its cardiac or cerebral receptors, is able to induce a spectacular cellular protection against ischemic injury. These cardioprotective and neuroprotective effects have been observed experimentally in rodents as well as clinically in humans. In particular, our team has demonstrated that the administration of NeoRecormon® protects the heart against ischemia in the rat by significantly improving its recovery.

In view of these exciting experimental results and of the growing interest of the scientific community for cytoprotective effects of EPO, we are planning the first clinical study examining the cardiac and cerebral protective effects of EPO (NeoRecormon®) in the setting of cardiac surgery.

• Drug: epoetin beta
  800UI/kg in 60ml of Nacl IV slow 1 to 3 hours before surgery
• Drug: placebo
  60ml of NaCl IV slow

• Experimental: 1
  epoetin beta
  Intervention: Drug: epoetin beta
• Placebo Comparator: 2
  placebo of NaCl
  Intervention: Drug: placebo

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• Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Lewczuk P, Stiefel M, Rustenbeck HH, Breiter N, Jacob S, Knerlich F, Bohn M, Poser W, Ruther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prange H, Cerami A, Brines M, Siren AL. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med. 2002 Aug;8(8):495-505.
• Johnsson P, Backstrom M, Bergh C, Jonsson H, Luhrs C, Alling C. Increased S100B in blood after cardiac surgery is a powerful predictor of late mortality. Ann Thorac Surg. 2003 Jan;75(1):162-8.
• Joyeux-Faure M, Godin-Ribuot D, Ribuot C. Erythropoietin and myocardial protection: what's new? Fundam Clin Pharmacol. 2005 Aug;19(4):439-46. Review.
• Kerbaul F, Giorgi R, Oddoze C, Collart F, Guidon C, Lejeune PJ, Villacorta J, Gouin F. High concentrations of N-BNP are related to non-infectious severe SIRS associated with cardiovascular dysfunction occurring after off-pump coronary artery surgery. Br J Anaesth. 2004 Nov;93(5):639-44. Epub 2004 Sep 3.

Inclusion Criteria:

• Coronary bypass surgery.
• Surgery not urgent.
• Left ventricular ejection fraction (LVEF) > 40.
• Informed consent form signed.

Exclusion Criteria:

• Valvular surgery.
• Surgery with beating heart, with or without cardiopulmonary bypass.
• Carotid bypass surgery.
• Myocardial infarction less than 30 days.
• Previous history of cardiac surgery.
• Kidney failure (creatinine > 200 µmol/l).
• Uncontrolled hypertension.
• Unstable angina.
• Risk of deep venous thrombosis.
• Vascular cerebral attack less than 30 days.
• Malignant tumour.
• Phenylketonuria.
• Allergy to erythropoietin.
• Previous programmed blood donation.
• Pregnancy and feeding.