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Effect of prophylactically administered edaravone during antegrade cerebral perfusion in a canine model of old cerebral infarction.

Suzuki T, Kazui T, Yamamoto S, Washiyama N, Ohkura K, Ohishi K, Bashar AH, Yamashita K, Terada H, Suzuki K, Akuzawa S, Fujie M

First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. tac.sz@hama-med.ac.jp

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. CONCLUSION: 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.

Published 26 February 2007 in J Thorac Cardiovasc Surg, 133(3): 710-6.
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