A rat EEG model for evaluating contrast media neurotoxicity.
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)
Adams
M D
MD
Diagnostic Products R & D, Mallinckrodt, Inc., Hazelwood, MO 63042.
Hopkins
R M
RM
Ferrendelli
J A
JA
D000818:Animals; D001921:Brain / Q000187:drug effects*; D003287:Contrast Media / Q000633:toxicity*; D004569:Electroencephalography; D005260:Female; D007472:Iohexol / Q000031:analogs & derivatives / Q000633:toxicity; D007482:Iothalamate Meglumine / Q000633:toxicity; D008793:Metrizamide / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D014283:Triiodobenzoic Acids / Q000633:toxicity
D003287:Contrast Media; D014283:Triiodobenzoic Acids; D007472:Iohexol; C036778:iogulamide; C054871:ioversol; D008793:Metrizamide; D007482:Iothalamate Meglumine