ISOFLURANE AND PENTOBARBITAL REDUCE THE FREQUENCY OF TRANSIENT ISCHEMIC DEPOLARIZATIONS DURING FOCAL ISCHEMIA IN RATS

Repetitive transient ischemic depolarizations (IDs) during focal cereb ral ischemia are thought to contribute to ischemic damage. Isoflurane and pentobarbital reduce injury (versus the nonanesthetized state) aft er focal cerebral ischemia. The mechanism by which these drugs reduce injury is not known. This protective effect might be mediated by a red uction in the number of IDs. We measured the frequency of IDs during f ocal cerebral ischemia in animals anesthetized with isoflurane or pent obarbital and compared it with that in N2O/fentanyl anesthetized anima ls and in animals in which the N-methyl-D-aspartate receptor antagonis t MK801 (dizocilpine) was given. Focal cerebral ischemia was induced b y the occlusion of the middle cerebral artery for a period of 2 h. Cor tical infarct volumes were determined after 3 h of reperfusion by imag e analysis of 2,3,5-triphenyl tetrazolium-stained coronal brain sectio ns. The infarct volume was significantly greater in the N2O/fentanyl g roup than in the other three groups. Infarct volumes in the isoflurane , pentobarbital, and MK801 groups were similar. The frequency of IDs w as significantly greater in the N2O/fentanyl group than in the other t hree groups, and was the least in the MK801 group. There was a direct correlation between the number of IDs and the volume of tissue injury. The data indicate that the protective effect of isoflurane and pentob arbital might, in part, be determined by their ability to reduce IDs d uring focal ischemia. However, the observation that the infarct volume was similar in the MK801, isoflurane, and pentobarbital groups, despi te a greater frequency of IDs in the latter two groups, suggests that mechanisms other than a simple reduction in the number of IDs probably also play a role in anesthetic-mediated cerebral protection. Implicat ions: Transient ischemic depolarizations during focal ischemia contrib ute to brain injury. Both isoflurane and pentobarbital reduced the fre quency of these depolarizations. Isoflurane-and pentobarbital-mediated reduction in the frequency of depolarizations might, in part, mediate the previously documented neuroprotective effect of these drugs.