Neurotoxic effects of water-soluble contrast agents on rat hippocampus: extracellular recordings

Synaptically evoked extracellular field potentials were obtained from the pyramidal cell layer of the Cal field of rat hippocampus slices. Synaptic activity was evoked by Schaffer's collateral stimulation. The effects of the water-soluble contrast agents Na-diatrizoate and metrizamide, as well as control solutions of NaCl and sucrose, were studied. Test solutions were 300-345 mOsm and had iodine concentrations of 3-30 mg I/ml. The effects of test solutions are apparent within 10 minutes and reversible within 30-45 minutes. Control recordings have a small positive potential, followed by a large negative spike and a final slow positive wave. Contrast agents have two effects. The first is an epileptogenic property characterized by repetitive negative spikes arising from an extended slow positive field. The second effect is a depression characterized by a reduction in the amplitude of the synaptically evoked fields, particularly the negative spikes. Na-diatrizoate predominately produces the first effect, while metrizamide principally produces the second. Hyperosmolar solutions only produce depression. These results correlate well with the clinical setting where Na-diatrizoate is a potent convulsant, while metrizamide produces symptoms compatible with neuronal depression. These results indicate that contrast agent seizure activity is not due to hyperosmolarity but to a more direct chemical effect. The depression, however, may be related to a hyperosmolar effect.