Myelography is a valuable diagnostic tool for disorders of the spinal canal. Water soluble radiopaque contrast media (CM) must be injected at concentrations from .4 to 1 M in order to produce adequate opacification. A new generation of nonionic CM have significantly reduced reactions to myelography, however, reactions are still common and our knowledge of the mechanisms involved is far from complete. The objective of this work is to identify the mechanisms involved in toxicity and to differentiate the dependence of toxicity on specific and generic CM properties. We and others have demonstrated that some CM cause significant metabolic disturbances. This effect does not appear to involve competition for the membrane glucose carrier. In the proposed work we will determine if the metabolic disturbance is a nonspecific effect on the carrier or if the CM is disturbing other cell functions which effect metabolism. Our preliminary data indicate that several of the CM have effects on electrolyte and neurotransmitter fluxes. In addition the dilution of CSF by the spinal injections of nonionic CM can disrupt electrolyte balance. In the proposed work we will quantify the disturbances in CSF composition and we will examine the distribution of CM in spinal cord and brain tissue. The effects measured will be correlated to the properties of the specific CM molecules examined. The experiments will involve in vivo rabbit models together will well established brain slice, cell culture and synaptosome models. The information available indicates substantial differences in the new CM, as well as possible further methods to reduce toxicity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019427-05
Application #
3399478
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1984-04-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
School of Medicine & Dentistry
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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