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This study was performed to assess the relative contributions of contrast medium osmolality and chemotoxicity to contrast-induced blood-brain barrier (BBB) damage. Experimental carotid angiography was carried out in rabbits with mannitol at an osmolality of 714 mOsm/kg, with the nonionic, monomeric contrast media iohexol and ioversol at similar osmolalities, and with the nonionic, dimeric contrast media iodixanol and iotrolan at osmolalities less than half that of the mannitol. The amount of damage caused by the procedure was assessed by determining the amount of intracerebral extravasation of intravascularly injected technetium-99m-pertechnetate. Mannitol caused no detectable BBB damage, but all four contrast media caused BBB damage that was significantly more severe than that caused by mannitol. The BBB damage caused by carotid angiography with iohexol, ioversol, iodixanol, and iotrolan was not attributable to their osmolalities, but due to some other physical and/or chemical effects of these media on the BBB.

Whisson CC, Evill CA, Sage MR, Wilson AJ. Effect of additional cations on the twitching reaction to intracarotid, nonionic contrast media in rabbits. Invest Radiol 1990;25:1004–1009. Previous investigations in this laboratory have confirmed the observation of facial muscle twitching during intracarotid injections of nonionic contrast media (CM) in rabbits. The reaction appears to be a locally mediated effect. To further investigate this reaction, cortical electroencephalogram (EEG) and facial electromyogram (EMG) recordings were made from rabbits receiving selective internal carotid artery (ICA) and external carotid artery (ECA) injections of CM. The effects of iopromide and iohexol were compared with and without the addition of sodium (Na) and calcium (Ca) ions at different concentrations. External carotid injections of iopromide also were performed in some animals paralyzed with D. tubocurarine to exclude the possibility that the reaction is due to an effect on peripheral nerves. The addition of between 5 and 20 mM Ca ions to both CM prevented the reaction but while the addition of Na ions (up to 150 mM) to iopromide had some preventative effect, it did not totally abolish the reaction. In those animals paralyzed with D-tubocurarine, the reaction to iopromide, as observed and recorded by EMG, was the same as that occurring in nonparalyzed animals. This finding is consistent with this reaction being independent of the peripheral nervous system.

The effect of intracarotid injections of methylglucamine iothalamate has been compared with that of mannitol solution of similar osmotic strength. The degree and distribution of blood-brain barrier disruption was assessed using Evans' Blue dye as a visual marker and by contrast enhancement measured by computer tomography (CT) scanner. Evans' Blue staining was found to match CT enhancement closely. It was also found that methylglucamine iothalamate injections resulted in significantly greater blood-brain barrier permeability. The relevance of these findings to chemotherapy of brain tumours is discussed briefly.