Neuroprotective Effect of Phenytoin and Hypothermia on a Spinal Cord Ischemic Injury Model in Rabbits.
- Author:
Sam Sae OH
1
;
Gheeyoung CHOE
;
Won Gon KIM
Author Information
1. Department of Thoracic and Cardiovascular Surgery, Sejong General Hospital, Korea.
- Publication Type:Original Article
- Keywords:
Ischemia;
Spinal cord;
Phenytoin
- MeSH:
Animals;
Constriction;
Hypothermia;
In Situ Nick-End Labeling;
Ischemia;
Motor Neurons;
Necrosis;
Neurologic Examination;
Neurons;
Neuroprotective Agents;
Phenytoin;
Rabbits;
Sodium Channels;
Spinal Cord;
Spinal Cord Ischemia
- From:The Korean Journal of Thoracic and Cardiovascular Surgery
2008;41(4):405-416
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Spinal cord ischemic injury during thoracic and thoracoabdominal aortic surgeries remains a potentially devastating outcome despite using various methods of protection. Neuronal voltage-dependent sodium channel antagonists are known to provide neuroprotection in cerebral ischemic models. This study was designed to compare the neuroprotective effects of phenytoin with those of hypothermia in a rabbit model of spinal cord ischemia. MATERIAL AND METHOD: Spinal cord ischemia was induced in New Zealand white rabbits by means of infrarenal aortic cross clamping for 25 minutes. Four groups of 8 animals each were studied. The control group and the hypothermia group received retrograde infusion of saline only (22degrees C, 2 mL/min); the normothermic phenytoin group and the hypothermicphenytoin group received retrograde infusion of 100 mg of phenytoin at different rectal temperatures (39degrees C and 37degrees C, respectively) during the ischemic period. The neurologic function was assessed at 24 and 72 hours after the operation with using the modified Tarlov criteria. The spinal cords were harvested after the final neurologic examination for histopathological examination to objectively quantify the amount of neuronal damage. RESULT: No major adverse effects were observed with the retrograde phenytoin infusion during the aortic ischemic period. All the control rabbits became severely paraplegic. Both the phenytoin group and the hypothermia group had a better neurological status than did the control group (p<0.05). The typical morphological changes that are characteristic of neuronal necrosis in the gray matter of the control animals were demonstrated by means of the histopathological examination, whereas phenytoin or hypothermia prevented or attenuated these necrotic phenomena (p<0.05). The number of motor neuron cells positive for TUNEL staining was significantly reduced, to a similar extent, in the rabbits treated with phenytoin or hypothermia. Phenytoin and hypothermia had some additive neuroprotective effect, but there was no statistical significance between the two on the neurological and histopathological analysis. CONCLUSION: The neurological and histopathological analysis consistently demonstrated that both phenytoin and hypothermia may afford significant spinal cord protection to a similar extent during spinal cord ischemia in rabbits, although no significant additive effects were noticed.
