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CYTOKINE RESPONSE TO ERYTHROPOIETIN IN CARDIAC SURGERY

¹ Department of Anesthesia and
² Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network, 200 Elizabeth Street, Toronto, Ontario

INTRODUCTION: Cardiac surgery is associated with a high risk of neurological sequelae that may be exacerbated by an inflammatory response. Evidence from models of experimental brain injury and ischemic stroke patients suggest that erythropoietin is neuroprotective. One mechanism for this neuroprotection proposes that alteration in the inflammatory response attenuates the secondary brain injury. The objective of this work was to determine if erythropoietin modifies the inflammatory response to cardiopulmonary bypass (CPB).

METHODS: Following REB approval 12 consecutive patients undergoing CPB were enrolled into one of 3 groups: Controls (n=6), 250 IU/kg EPREX (r-huEPO) (n=3), and 500 IU/kg r-huEPO (n=3). R-huEPO was given immediately before induction of anaesthesia. Samples for measurement of IL-6, IL-10 and TNF- were drawn 10 min before induction of anesthesia, 5 min after sternotomy, 45 min after initiation of CPB, and 45 min, 6 hours and 18 hours after separation from CPB. The IL-6, IL-10 and TNF- levels were measured from serum with an Enzyme Amplified Sensitivity Immunoassay (EASIA, Biosource, Nivelles, Belgium). An ANOVA and Duncan post hoc test was used to compare cytokine levels at each time point.

RESULTS: Levels of IL-6 (Table Below) and IL-10 were higher than control subjects while on CPB. There was no difference in the levels of TNF- between treatment groups at any time point.

Plasma IL-6 Control (pg/ml) EPO 250 IU/kg (pg/ml) EPO 500 IU/kg (pg/ml) Pre CPB (After Sternotomy) ND 93 ± 161 2.6 ± 4.6 On CPB (45 min on CPB) 283 ± 291 1388 ± 208* 1789 ± 1111* Post CPB (45 min after CPB) 382 ± 589 304 ± 176 206 ± 37 ND = Not detectable * P < 0.05

DISCUSSION: The administration of r-huEPO in patients undergoing cardiac surgery results in an alteration of the inflammatory response to CPB. The consequence of these changes remains to be clarified.

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