Frigeni Viviana, Samuelli Giovanni, Miragoli Luigi, Grotti Adriana, Lorusso Vito
Milano Research Centre, Bracco Imaging SpA, Milan, Italy.
Invest Radiol. 2002 Apr;37(4):222-31. doi: 10.1097/00004424-200204000-00008.
All contrast agents should be neurologically safe because although some are not indicated for procedures, such as myelography, just the same they may come in contact with nervous tissue during contrast-enhanced imaging. This is because even when they are intravascularly injected, the presence of undiagnosed blood-brain barrier damage may allow them to penetrate the brain barrier. In the present study, we investigated the neurologic safety of iomeprol by studying in vitro its potential effects on the central nervous system (CNS) synaptic transmission. Other widely used x-ray contrast agents were also assessed for comparative purposes.
CNS synaptic transmission was evaluated in terms of evoked field potentials recorded from the pyramidal region of rat hippocampal slices. The field potentials were evoked by electrical stimulation of the Schaffer collateral pathway. The effects of the contrast agents were evaluated in terms of number and amplitude of population spikes (PS) and as the maximal slope of the excitatory postsynaptic potentials (EPSP). The contrast agents were tested at final concentrations of 3, 10, and 30 mg(iodine)/mL in iso-osmolal condition with respect to artificial cerebrospinal fluid (CSF).
Iomeprol, like ioversol, principally exerted a mild inhibitory effect on CNS synaptic transmission, an effect that was preceded by a weak, transient excitation. Iopentol exerted a rapid and complete inhibition of synaptic transmission without showing any excitatory effects. Iobitridol, though belonging to the nonionic monomeric class, exerted, surprisingly, an epileptogenic action at the highest concentration, whereas its inhibitory action was slow and mild. Diatrizoate, as expected, exerted an epileptogenic activity even at the lowest concentration, followed by a marked inhibitory action. Ioxaglate, as expected because it is an ionic though dimeric contrast agent, exerted an epileptogenic action at the intermediate concentration, whereas it barely demonstrated an inhibitory effect at all. All the contrast agent effects observed in the study reversed or tended to reverse during washout.
Even taking in account the limitation because of the use of an in vitro approach and high contrast agent concentrations, we can conclude that the positive neuro-tolerability of iomeprol is further confirmed by this model as it proved to be devoid of epileptogenic activity and, among the contrast agents exhibiting inhibitory action, it was the contrast agent with the least amount of activity. In addition, contrary to that generally reported in the literature, nonionic, low osmolal contrast agents are not all identical in their neuro-tolerability when assessed in the rat hippocampal slice model.
所有造影剂在神经学上都应是安全的，因为尽管有些造影剂并不适用于某些检查程序，如脊髓造影，但在增强造影成像过程中它们仍可能与神经组织接触。这是因为即使它们是通过血管内注射，未被诊断出的血脑屏障损伤的存在可能会使它们穿透脑屏障。在本研究中，我们通过体外研究碘海醇对中枢神经系统（CNS）突触传递的潜在影响，来探究其神经学安全性。为作比较，还评估了其他广泛使用的X射线造影剂。
通过记录大鼠海马切片锥体区域诱发的场电位来评估CNS突触传递。场电位由电刺激海马伞通路诱发。根据群体峰电位（PS）的数量和幅度以及兴奋性突触后电位（EPSP）的最大斜率来评估造影剂的作用。造影剂在相对于人工脑脊液（CSF）等渗的条件下，以3、10和30mg（碘）/mL的终浓度进行测试。
碘海醇与碘佛醇一样，主要对CNS突触传递产生轻度抑制作用，在这种作用之前有微弱的、短暂的兴奋。碘喷托对突触传递产生快速且完全的抑制，未表现出任何兴奋作用。碘比醇虽然属于非离子单体类造影剂，但令人惊讶的是，在最高浓度时它具有致癫痫作用，而其抑制作用缓慢且轻微。泛影酸盐正如预期的那样，即使在最低浓度时也具有致癫痫活性，随后是明显的抑制作用。碘克沙醇，由于它是一种离子型二聚体造影剂，正如预期的那样，在中等浓度时具有致癫痫作用，而几乎未表现出任何抑制作用。在研究中观察到的所有造影剂的作用在冲洗过程中都发生了逆转或趋于逆转。
即使考虑到由于使用体外方法和高造影剂浓度所带来的局限性，我们仍可以得出结论，该模型进一步证实了碘海醇良好的神经耐受性，因为它被证明没有致癫痫活性，并且在表现出抑制作用的造影剂中，它是活性最小的造影剂。此外，与文献中普遍报道的情况相反，在大鼠海马切片模型中评估时，非离子型、低渗造影剂的神经耐受性并不都相同。
