Erythropoietin protects the central nervous system during prolonged hypothermic circulatory arrest: an experimental study in a canine model.
OBJECTIVE
Current data suggest that erythropoietin protects the brain and the spinal cord from ischemic and traumatic injury. In this study, we determined whether erythropoietin protects the central nervous system during prolonged hypothermic circulatory arrest in an experimental canine model.


METHODS
Ten adult beagle dogs were randomly and intravenously injected with either 5000 U/kg recombinant human erythropoietin or normal saline. Each dog was then subjected to a cardiopulmonary bypass and 120 minutes of deep hypothermic circulatory arrest (18 degrees C). The level of tau proteins in the cerebrospinal fluid, a modified marker of neurologic deficit in dogs, and the histopathologic characteristics of the brains and spinal cords were then examined.


RESULTS
The level of tau proteins was significantly lower in the erythropoietin-treated group than in the untreated group at 6 hours (20 +/- 12 vs 144 +/- 54 pg/mL; P = .036) and 12 hours (64 +/- 35 vs 478 +/- 103 pg/mL; P = .01) after the operation. The total Neurologic Deficit Score was 59 +/- 31 (0, normal; 500, brain death) in the erythropoietin-treated group, compared with 376 +/- 30 in the untreated group (P = .0117). Histopathologic examination revealed that ischemic neuronal changes and apoptosis in the hippocampus CA1 were significantly lower in the erythropoietin-treated group (P < .01 and P = .028, respectively).


CONCLUSIONS
This study showed that erythropoietin protected the central nervous system during prolonged hypothermic circulatory arrest, partly by preventing both necrosis (ischemic neuronal changes) and apoptosis.
Kawata
Mitsuhiro
M
Department of Cardiothoracic Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. mkawata-ths@umin.ac.jp
Takamoto
Shinichi
S
Kitahori
Kazuo
K
Tsukihara
Hiroyuki
H
Morota
Tetsuro
T
Ono
Minoru
M
Motomura
Noboru
N
Murakami
Arata
A
Suematsu
Yoshihiro
Y
D000818:Animals; D002493:Central Nervous System Diseases / Q000209:etiology* / Q000517:prevention & control*; D004285:Dogs; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D008297:Male; D011994:Recombinant Proteins; D013997:Time Factors
D011994:Recombinant Proteins; D004921:Erythropoietin