Summary: Anoxic depolarization (AD) and failure of ion homeostasis play an important role in ischemia-induced neuronal injury. In the present study, different drugs with known ion-channel-modulating properties were examined for their ability to interfere with cardiac-arrest-elicited AD and with the changes in the extracellular ion activity in rat brain. Our results indicate that only drugs primarily blocking membrane Na + permeability (NBQX, R56865, and flunarizine) delayed the occurrence of AD, while compounds affecting cellular Ca 2 + load (MK-801 and nimodipine) did not influence the latency time. The ischemia-induced [Na +]e reduction was attenuated by Anoxic depolarization (AD) is a well known phe nomenon occurring if tissue energy supply ceases for a certain time. The normal compartmentation of ions between the intra-and extracellular space breaks down and the cerebral direct current (DC) potential exhibits a sudden negative shift (Hansen, 1985). Previous studies have shown that the sever ity of the ischemic neuronal injury was significantly correlated with the time period during which the brain tissue was in a depolarized state (Balestrino et ai., 1989; Somjen et ai., 1990; Gill et ai., 1992). Some drugs beneficial in the treatment of cerebral ischemia are able to delay the occurrence of AD (Balestrino and Somjen, 1986; Holler et ai., 1986). Therefore, the latency from onset of ischemia until occurrence of AD has been considered an indicator for the tissue resistance against ischemic insults (Bures and Buresova, 1957).However, for an effective search of antiischemic drugs and to get a plausible explanation of the drug properties needed to delay the occurrence of AD, better understanding of this phenomenon is re quired. A primary event upon cerebral ischemia preceding and coinciding with AD is the change in membrane ion permeability. The present study is an attempt to investigate which types of ion channels are involved before, during, and after the negative DC shift and whether the ischemia-induced ion movements influence the latency time from onset of ischemia until the occurrence of AD. For this pur pose, we examined the effects of selected com pounds with known ion-channel-modulating proper ties in a rat model of global cerebral ischemia in duced by cardiac arrest. MATERIALS AND METHODS Animal preparationMale Wi star rats (230-280 g body wt) were anesthetized by intraperitoneal injection of urethane 0.2-2.0 glkg).Femoral artery and vein were cannulated to monitor ar terial blood pressure, collect blood samples, and apply drugs. The rectal temperature was kept at 37.5°C by means of a warm water blanket surrounding the' animal body. The animals were immobilized by intravenous in jection of succinylcholine and artificially ventilated with 0 2 /N 2 (30:70) gas mixture. A hole of 3-mm diameter was drilled in the parietal skull. A double-or triple-barrel glass
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