Hoppe, James O.; Archer, S.
June 1960
Angiology;Jun1960 Part 2, Vol. 11 Issue 3, p244
Academic Journal
1. The properties and methods for evaluating x-ray contrast media for cardiovascular angiography were discussed. The cardiovascular angiographic contrast media consist of two distinct types: (a) the peripheral vascular angiographic or urographic media, which are aqueous solutions containing 30 per cent to approximately 50 per cent of x-ray contrast medium and (b) the angiocardiographic media, which are also aqueous solutions but contain from 70 to 90 per cent of x ray contrast medium. The use of urographic of peripheral vascular angiographic media in angiocardiography provides x-ray pictures of inadequate density, whereas the use of angiocardiographic media in urography is physiologically unjustified. 2. Of the various properties of the cardiovascular angiographic contrast medium, the most important, and also most difficult to attain, is that of low systemic and local tissue toxicity at the required level of radiopacity. 3. Of four different radiopaques of this type investigated, the least toxic compound was found to be diatrizoate sodium. Acute intravenous LD50 values in the mouse, rat, rabbit, cat and dog were found to range from 11,300 to 14,000 mg per kg for diatrizoate sodium; from 5,200 to 9,100 mg per kg for sodium acetrizoate; from 4,500 to 7,200 mg per kg for .sodium iodomethamate and from 2,800 to 6,400 mg per kg for iodopyracet. 4. Local tissue toxicity, as indicated by breakdown of the blood brain barrier studies in the rabbit, was minimal with iodopyracet, 35 per cent, and diatrizoate sodium, 50 per cent; antl extensive with sodium iodomethamate, 50 per cent; iodopyracet, 70 per cent; and sodium acetrizoate, 30 and 50 per cent. 5. The acute toxicity of these compounds was found to differ markedly. depending on whether they were injected intravenously or intracisternally at the cisterna cerebellomedularis in animals. In contrast to the LD50 values of 2,800 to 13,200 mg per kg observed following intravenous injection in the rabbit, cat and dog, the LD50 values after intracisternal injections in these same species were found to range from 7.9 to 30 mg per kg. Vigorous clonic-tonic convulsions, similar in pattern to those observed after intravenous injection, were observed. The extensive pulmonary changes noted after intravenous injection of massive supradiagnostic doses were not observed following intracisternal injection. 6. The intracisternal toxicity of diatrizoate sodium, sodium acetrizoate and iodopyracet was reduced by from 20 to 800 per cent in the rabbit, eat and dog under sodium pentobarbital anesthesia. 7. The nature of the rare serious reaction with the cardiovascular angiographic contrast medium in man was discussed. It was suggested, in view of the marked difference in the toxicity of these radiopaques by intravenous and intracisternal injection in animals, that an additional factor involved in the rare fatal reaction in man may arise from an intrinsic susceptibility to breakdown of the blood-brain barrier by the cardiovascular angiographic contrast medium. 8. A review of the development of radiopaques for the diagnostic visualization of the heart and great blood vessels from the laboratory point of view has indicated several important contributions to the search for safer and more effective x-ray contrast media for cardiovascular angiography, particularly within the past decade.


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