The Erythropoietin NeuroProtective Effect: Assessment in CABG Surgery (TENPEAKS)

Abstract

Background and Purpose-Neurocognitive dysfunction complicates coronary artery bypass surgery. Erythropoietin may be neuroprotective. We sought to determine whether human recombinant erythropoietin would reduce the incidence of neurocognitive dysfunction after surgery. Methods-We randomly assigned 32 elective first-time coronary artery bypass graft patients to receive placebo or 375 U/kg, 750 U/kg, or 1500 U/kg of recombinant human erythropoietin divided in 3 daily doses, starting the day before surgery. Primary outcomes were feasibility and safety, and secondary outcomes were neurocognitive dysfunction at discharge and 2 months. Results-All subjects were male, mean age 60 years (range 46 to 73). No significant differences were found in pump time, cross-clamp time, or hospital length of stay. Mortality and pure red cell aplasia were not observed. One patient in the 375 U/kg group had ST changes compatible with myocardial injury immediately postoperative, but no other thrombotic complications were observed. Neurocognitive dysfunction occurred in 21/32 (66%) of patients at discharge and 5/32 (16%) at 2 months. Neurocognitive dysfunction at discharge by group was: placebo 6/8 (75%), 375 U/kg 4/8 (50%), 750 U/kg 6/8 (75%), and 1500 U/kg 5/8 (63%). Neurocognitive dysfunction at 2 months by group was: placebo 3/8 (38%), 375 U/kg 1/8 (13%), 750 U/kg 1/8 (13%), and 1500 U/kg 0/8 (0%). Neurocognitive dysfunction at 2 months for erythropoietin at any dose was 2/24 (8.3%) versus 3/8 (38%) for placebo (Pϭ0.085). Conclusions-This

Neuroprotective effects of erythropoietin on Alzheimer’s dementia model in rats

“…19 Indeed, in clinical studies, chronic treatment with rhEPO improved neurocognitive dysfunction in patients with schizophrenia 20 and multiple sclerosis 21 as well as with prematurity 22 and coronary artery surgery. 23 The degeneration of basal forebrain cholinergic neurons and the associated defects of central cholinergic neurotransmission into the cerebral cortex and other areas have been suggested as the principal cause of cognitive dysfunction in AD. 24 ChAT is one of the specific cholinergic marker proteins for the function of cholinergic neurons, which are responsible for ACh synthesis in these neurons.…”

Apoptosis during CABG surgery with the use of cardiopulmonary bypass is prominent in ventricular but not in atrial myocardium

“…19 However, expression of EPO and EPOR is rapidly increased in response to hypoxia and increased reactive oxygen species. 20,21 Numerous studies have shown that EPO has cytoprotective effects [22][23][24] and EPOR signalling pathways are associated with cell survival. [25][26][27][28] Since EPO reduces apoptosis, we postulate that EPO administration may have salutary effects on the heart in the setting of cardiac surgery employing CPB and cardioplegic arrest.…”

Impact of Erythropoietin on Intensive Care Unit Patients

“…Neurocognitive dysfunction can also complicate CABG surgery. In a small double-blind, placebo controlled, proof-of-concept trial, treatment with high doses of rhEpo (up to 1,500 IU/kg bw, divided in 3 daily doses, starting the day before surgery), the postoperative cognitive decline did not differ statistically between rhEpo-treated patients and controls, and there were no benefits with respect to the mortality rate [90]. Likewise, an interventional study in high-risk ICU patients revealed that rhEpo treatment (500 IU/kg bw.…”