Abstract
Since the discovery of opiate receptors in the central nervous system, there have been a few reports which indicated an important role of endogeneous opiate substances in cerebrovascular diseases. The purpose of the present study is to investigate the effects of pure opiate antagonist, naloxone, on experimental ischemia in gerbils.
Under light anesthesia with sodium pentobarbital, the right common carotid artery was ligated and the all animals were decapitated two hours after the ligation. One hundred and eighty nine animals were used in the present study.
Unilateral common carotid artery ligation produced neurologic deficits, i.e. hemiparesis, abnormal circling behavious, in about one third of the animals.
After the intraperitoneal injection of naloxone (1 mg/kg), transient reversal of ischemic neurologic deficits, which started within three to five minutes and lasted about fifteen minutes, were observed.
Regional cerebral blood flow measured by hydrogen clearance method decreased with naloxone administration in the sham operated animals. By contrast, cerebral blood flow significantly increased after the naloxone injection in the carotid ligated animals with neurologic deficits, in which cerebral blood flow was already diminished before the administration of the agent.
The animals with neurologic deficits showed a marked increase of both water content and Na/K ratio in the ischemic hemisphere, but these abnormal findings were improved by the administration of naloxone. In the contralateral hemisphere of the same animals, a significant but less remarkable increase of water content and Na/K ratio was also observed. The administration of naloxone resulted in a significant decrease of NaiK ratio but no change in water content of the contralateral hemisphere. Injection of naloxone made no significant changes in arterial blood pressure, Pao2, Paco2 and pH.
These findings suggest that naloxone improves both cerebral metabolism and brain edema in the acute stage of cerebral ischemia with the antagonistic effect on the opiate substances which are known to increase in the ischemic brain. Furthermore, these data may indicate a possible role of the opiate system in the reduction of cerebral metabolism observed in the contralateral hemisphere.
