Effect of prophylactically administered edaravone during antegrade cerebral perfusion in a canine model of old cerebral infarction.
OBJECTIVE
Reactive free radical species are thought to be involved in postoperative neurologic dysfunction after antegrade selective cerebral perfusion in brains with old infarction. We assessed the brain protective effect of prophylactically administered edaravone, a free radical scavenger, for antegrade selective cerebral perfusion in brains with or without old infarction in a canine model.


METHODS
A canine model of old cerebral infarction was created by injecting cylindric silicone embolus into the middle cerebral artery. Animals showing obvious neurologic deficits and surviving 4 weeks or longer were included in the model. Deep hypothermia with antegrade selective cerebral perfusion was performed in both intact (non-edaravone, group A; edaravone-treated, group B) and infarcted animals (non-edaravone, group C; edaravone-treated, group D). Serum concentrations of malondialdehyde, hexanoyl-lysine, glutamate, and venous-arterial lactate difference were measured, and central conduction time and amplitude of somatosensory evoked potentials were assessed during the operation.


RESULTS
Compared with the intact groups, serum concentrations of malondialdehyde and hexanoyl-lysine in group C significantly increased at the end of antegrade selective cerebral perfusion, whereas that of glutamate did so in the rewarming phase. Increases in all these biochemical parameters were suppressed in group D. In group C, the venous-arterial lactate difference was significantly greater in the rewarming phase at 28 degrees C compared with intact groups. A significant prolongation of postoperative central conduction time and decrease in neuronal activity were detected in group C, both of which recovered in group D.


CONCLUSIONS
Prophylactic administration of edaravone exerted a significant protective effect against postoperative neurologic dysfunction after antegrade selective cerebral perfusion in a canine model with old cerebral infarction.
Suzuki
Takayasu
T
First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. tac.sz@hama-med.ac.jp
Kazui
Teruhisa
T
Yamamoto
Seiji
S
Washiyama
Naoki
N
Ohkura
Kazuhiro
K
Ohishi
Kentaro
K
Bashar
Abul Hasan Muhammad
AH
Yamashita
Katsushi
K
Terada
Hitoshi
H
Suzuki
Kazuchika
K
Akuzawa
Satoshi
S
Fujie
Michio
M
D000704:Analysis of Variance; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001774:Blood Chemical Analysis; D002315:Cardiopulmonary Bypass / Q000379:methods; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000601:surgery; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000077553:Edaravone; D005073:Evoked Potentials, Somatosensory; D005260:Female; D007262:Infusions, Intravenous; D011300:Preoperative Care / Q000379:methods; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D015424:Reperfusion / Q000379:methods*; D015427:Reperfusion Injury / Q000517:prevention & control; D012680:Sensitivity and Specificity
D000077553:Edaravone; D000983:Antipyrine