Potential neuroprotective benefits of erythropoietin during experimental hypothermic circulatory arrest.
OBJECTIVE
Recent studies have shown that erythropoietin protects neurons from glutamate toxicity and ischemia. This study was performed to evaluate the potential neuroprotective effect of erythropoietin during experimental hypothermic circulatory arrest.


METHODS
Twenty pigs were randomized to receive intravenously either 500 IU/kg recombinant human erythropoietin or saline before a 75-minute period of hypothermic circulatory arrest at an intracerebral temperature of 18 degrees C.


RESULTS
After the administration of erythropoietin, its concentration in the cerebrospinal fluid increased 4.5-fold 8 hours after the start of rewarming, whereas it did not increase in control animals. The 7-day survival rate was 60% in the erythropoietin group and 70% in the control group (P = 1.0). No significant differences were observed between the study groups in terms of electroencephalography, behavioral score, and histopathologic score. The erythropoietin group had higher vascular resistance and mean arterial pressure values, lower intracerebral concentrations of glutamate and glycerol, higher brain tissue oxygen tension, and lower apoptotic index.


CONCLUSIONS
Administration of 500 IU/kg erythropoietin intravenously before hypothermic circulatory arrest was followed by an increased erythropoietin concentration in the cerebrospinal fluid. Although previous studies have demonstrated neuroprotective effects of erythropoietin during brain ischemia, the present study, using a chronic porcine model, failed to show any significant benefit after administration of erythropoietin in terms of mortality or brain histopathology. Lower intracerebral concentrations of glutamate and glycerol, higher brain tissue oxygen tension, and lower apoptotic index observed in the erythropoietin group, however, suggest that a distinct neuroprotective effect of erythropoietin might be achieved at different dosages and timing of administration.
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004569:Electroencephalography; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D007036:Hypothermia, Induced / Q000009:adverse effects*; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D015996:Survival Rate; D013552:Swine
D018696:Neuroprotective Agents; D004921:Erythropoietin; D018698:Glutamic Acid