Adams M D, Hopkins R M, Ferrendelli J A
Diagnostic Products R & D, Mallinckrodt, Inc., Hazelwood, MO 63042.
Invest Radiol. 1988 Sep;23 Suppl 1:S217-9. doi: 10.1097/00004424-198809001-00044.
The electroencephalographic (EEG) effects of intracisternally administered x-ray contrast media were evaluated in rats as a means of assessing neurotoxicity. Rats were ventilated with a mixture of nitrous oxide and oxygen (70/30) sufficient to maintain light anesthesia/analgesia and neuromuscular blockade was induced to prevent movement artifacts. A femoral artery was catheterized for monitoring arterial blood pressure (BP), heart rate, blood gases, and pH. Four 22-gauge stainless steel needle electrodes were inserted underneath the scalp for recording EEG. Approximately 1 hour after the start of EEG recording, test agents were injected via the cisterna magna and rats were placed in a 20 degrees head-down position. EEG and BP were monitored continuously for up to 160 minutes postinjection. Blood gases and pH were monitored periodically. The effects of meglumine iothalamate (IOT), metrizamide (MET), iogulamide (IOG), and ioversol (IOV) were compared at dose levels from 30 to 240 mgI/kg. Normal saline was injected as a control substance and caused no changes in EEG, blood gases, pH, and BP for up to 160 minutes postinjection. IOT (30 mg I/kg) produced profound EEG effects consistent with epileptogenic activity, followed by slowing and subsequent death in 3 of 4 animals. Metrizamide had minimal EEG effects at 30 mg I/kg but at 60 mg I/kg, and 120 mg I/kg produced moderate to severe EEG changes including epileptiform patterns and death in 33% of animals. IOV caused mild EEG abnormalities in 4 of 12 animals at 120 mg I/kg, mild EEG abnormalities in 6 of 11 animals, and moderate EEG abnormalities in 1 of 11 animals at 240 mg I/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
通过评估大鼠脑池内注射X射线造影剂后的脑电图(EEG)效应,作为一种评估神经毒性的方法。用一氧化二氮和氧气的混合气体(70/30)对大鼠进行通气,以维持轻度麻醉/镇痛,并诱导神经肌肉阻滞以防止运动伪影。插入一根股动脉导管以监测动脉血压(BP)、心率、血气和pH值。在头皮下插入四个22号不锈钢针电极用于记录脑电图。脑电图记录开始约1小时后,通过枕大池注射受试药物,并将大鼠置于头向下20度的位置。注射后连续监测脑电图和血压长达160分钟。定期监测血气和pH值。比较了不同剂量水平(30至240 mgI/kg)的碘他拉葡胺(IOT)、甲泛葡胺(MET)、碘谷胺(IOG)和碘海醇(IOV)的效应。注射生理盐水作为对照物质,在注射后长达160分钟内,脑电图、血气、pH值和血压均无变化。IOT(30 mg I/kg)产生与致痫活性一致的明显脑电图效应,随后4只动物中有3只出现脑电减慢并随后死亡。甲泛葡胺在30 mg I/kg时脑电图效应最小,但在60 mg I/kg和120 mg I/kg时,会产生中度至重度脑电图变化,包括癫痫样波形,且33%的动物死亡。IOV在120 mg I/kg时,12只动物中有4只出现轻度脑电图异常;在240 mg I/kg时,11只动物中有6只出现轻度脑电图异常,1只出现中度脑电图异常。(摘要截断于250字)