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J Thorac Cardiovasc Surg 2002;124:714-723
© 2002 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology (CSP)

Potential neuroprotective benefits of erythropoietin during experimental hypothermic circulatory arrest

From the Departments of Surgery,^a Anesthesiology,^b and Forensic Medicine,^c Oulu University Hospital, University of Oulu, Oulu, Finland.

This study was supported by grants from the Oulu University Hospital, Oulu University, the Finnish Foundation for Cardiovascular Research, and the Sigrid Juselius Foundation.

Received for publication Dec 13, 2001. Revisions requested Jan 8, 2002; revisions received Jan 10, 2002. Accepted for publication Feb 10, 2002. Address for reprints: Tatu Juvonen, MD, PhD, Department of Surgery, Oulu University Hospital, PO Box 22, 90221 Oulu, Finland (E-mail: tatu.juvonen{at}oulu.fi).

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°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.

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