Bryan R N, Hershkowitz N
Invest Radiol. 1984 Jul-Aug;19(4):329-32. doi: 10.1097/00004424-198407000-00018.
The in vitro rat hippocampus slice preparation has been utilized to examine the direct neurotoxicity of water-soluble contrast agents. Intraneuronal recordings were obtained from pyramidal cells in the CA1 field of rat hippocampus slices. Synaptic activity was evoked by Schaffer's collateral stimulation. The effects of Na-diatrizoate and metrizamide were studied. Test solutions were 300 to 345 mOsm and had iodine concentrations of 22.5 to 30 mg I/ml which are probably near clinical concentrations. The two effects of the contrast agents are apparent within 10 minutes and reversible within 30 to 45 minutes. The first is an epileptogenic property reflected by repetitive action potentials arising from an early prolonged depolarization. The second effect is a depression of electrical activity characterized by hyperpolarization of the resting membrane potential. Na-diatrizoate predominantly produced the first effect. Metrizamide principally produced the second effect. These results indicate that contrast agent seizure activity is not due to hyperosmolarity but a more direct chemical effect. The depression, however, may be related to a hyperosmolar effect. The differences between the dominant effects of the ionic vs. nonionic agents observed in these experiments seem to correlate with clinical experience and may indicate the etiology of central nervous system neurotoxicity of these drugs.
体外大鼠海马切片制备已被用于检测水溶性造影剂的直接神经毒性。从大鼠海马切片CA1区的锥体细胞进行细胞内记录。通过刺激Schaffer侧支来诱发突触活动。研究了泛影酸钠和甲泛葡胺的作用。测试溶液的渗透压为300至345 mOsm，碘浓度为22.5至30 mg I/ml，这可能接近临床浓度。造影剂的这两种作用在10分钟内明显，在30至45分钟内可逆。第一种是由早期延长去极化产生的重复动作电位所反映的致痫特性。第二种作用是电活动抑制，其特征为静息膜电位超极化。泛影酸钠主要产生第一种作用。甲泛葡胺主要产生第二种作用。这些结果表明，造影剂的癫痫发作活动不是由于高渗性，而是更直接的化学作用。然而，这种抑制可能与高渗作用有关。在这些实验中观察到的离子型与非离子型造影剂主要作用之间的差异似乎与临床经验相关，并且可能表明这些药物引起中枢神经系统神经毒性的病因。
