With the introduction of metrizamide, the first commercially available non-ionic contrast medium, many of the serious reactions associated with water-soluble, ionic agents have been eliminated. However, minor adverse reactions are still commonly encountered with metrizamide and a few major reactions have also occurred. To study the effects on the central nervous system (CNS) of non-ionic contrast media, we will perform a series of experiments with metrizamide and iohexol in an attempt to grade their toxicity and explain why these side effects occur, how they might be aggravated by various circumstances and how these risks might be decreased. We propose to do this by studying the penetration and localization of these two contrast media in the CNS since we believe penetration, which depends on the concentration of the contrast medium in the cerebrospinal fluid (CSF) and the time it is in contact with nervous tissue, is the basis of toxicity. We also propose to study the possible interference of metrizamide with the glucose metabolism of the CNS, and the stability of metrizamide in vivo as well as in vitro. We plan to study means of decreasing penetration of metrizamide into the CNS, and ways of avoiding interference in glucose metabolism as well as comparative behavior of iohexol and metrizamide. The major goals of the proposed work are: 1) a better understanding of the drainage of contrast media from the subarachnoid space, 2) an evaluation of degree of penetrance into the CNS, for both metrizamide and iohexol, under """"""""normal"""""""" circumstances and after changing the rate of production of CSF, 3) a better understanding of the mechanism by which metrizamide produces side effects, which could help in designing of less toxic contrast media 4) an evaluation and comparison of toxicity of metrizamide and iohexol, as measured by disturbance in neuronal metabolism. A better understanding of the mechanism and factors influencing contrast media toxicity will allow us to contribute to decreasing side effects in future examinations of the subarachnoid space.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019427-02
Application #
3399476
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1984-04-01
Project End
1987-03-30
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Medicine
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Marinetti, G V; Morris, T W; Leaky, P (1993) Effects of Ca2+, Mg2+, and depolarizing agents, on the 32Pi-labeling and degradation of phosphatidylinositols in rat brain synaptosomes. Neurochem Res 18:345-51
Marinetti, G V; Morris, T W; Ekholm, S E et al. (1992) Effects of radiopaque contrast media on calcium uptake and phosphatidylinositol metabolism in rat brain synaptosomes. Invest Radiol 27:224-9
Morris, T W; Ekholm, S E; Marinetti, G V et al. (1991) Gd-DTPA and Gd-DOTA effects on metabolism of glucose and phosphatidylinositols. Invest Radiol 26 Suppl 1:S209-11;discussion S232-5
Morris, T W; Ekholm, S E; Prentice, L I (1991) The effects of gadolinium-DTPA and -DOTA on neural tissue metabolism. Invest Radiol 26:1087-90
Ekholm, S E; Morris, T W; Marinetti, G V (1990) Effects of contrast media on synaptosomal phosphatidylinositols. Invest Radiol 25 Suppl 1:S84-5
Ekholm, S E; Morris, T W; Prentice, L et al. (1990) Local glucose utilization changes caused by subarachnoid contrast media in the rabbit. Acta Radiol 31:209-12
Sahler, L G; Morris, T W; Katzberg, R W et al. (1990) Microangiography of the rabbit temporomandibular joint in the open and closed jaw positions. J Oral Maxillofac Surg 48:831-4
Morris, T W; Ekholm, S E; Prentice, L et al. (1989) Iotrol, iodixanol, and 2-deoxy-D-glucose effects on neural tissue CO2 production. AJNR Am J Neuroradiol 10:1123-6
Ekholm, S E; Morris, T W; Fonte, D et al. (1989) Effects of contrast media on neural tissue glucose uptake in vitro. Invest Radiol 24:145-9
Simon, J H; Ekholm, S E; Morris, T W et al. (1987) Further support for the glucose hypothesis of metrizamide toxicity. The effect of metrizamide and glucose analogue-free contrast media on hexokinase. Invest Radiol 22:137-40

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