Neurologic injury that occurs after ischemia results from a cascade of events involving the release of various endogenous neurotoxins. A portion of the release of excitatory neurotransmitters is calcium dependent and may be attenuated by administration of calcium channel blockers. Using an in vivo model of ischemia, we studied the effects of omega-conopeptide MVIIC, a voltage-sensitive calcium channel blocker, and hypothermia (32 degrees C) on hippocampal glutamate and aspartate release in the peri-ischemic period. Thirty-four New Zealand white rabbits of either sex were anesthetized with halothane, intubated, and mechanically ventilated. Monitored variables included blood gases, mean arterial blood pressure, and the electroencephalogram. Microdialysis catheters were transversely inserted through the anterior portion of the dorsal hippocampus and perfused with artificial cerebrospinal fluid at a rate of 2 microliters/min. After stabilization period, animals were randomly assigned to one of the following groups: Control group (n = 8), 10 microM omega-conopeptide MVIIC group (n = 7), 100 microM omega-conopeptide MVIIC group (n = 7), Hypothermia group (n = 6; cranial temperature = 32 degrees C), and omega-conopeptide MVIIC + hypothermia group (n = 6; 100 microM omega-conopeptide MVIIC and cranial temperature 32 degrees C). All the rabbits were subjected to 10 minutes of global cerebral ischemia produced by neck tourniquet inflation combined with hypotension during halothane anesthesia. Conopeptide MVIIC was administered in the artificial cerebrospinal fluid used to perfuse the microdialysis catheter. In control animals, ischemia caused a significant increase in glutamate (9.7 fold) and aspartate (11.3 fold) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)